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(TTA)35
?
-
trinucleotide repeat (TTA)35 lying in the intergenic region of chromosome XIII of Saccharomyces cerevisiae, between the RPM2 (RNase P mitochondrial 2) and PRE8 genes. This sequence contains the structural elements suitable to be susceptible to DNA topoisomerase I site-specific activity and to assemble nucleosomes. DNA topoisomerase I strongly recognizes the TTA repeats. The (TTA)35 repeat is engaged in a positioned nucleosome in vivo. DNA topoisomerase I efficiently reacts with the TTA repeat, the (TTA)35 sequence, the longest and most stable among the simple repeated sequences in Saccharomyces cerevisiae, is organized in a positioned nucleosome and this can possibly account for its high stability, in fact each nucleosome stores one negative supercoil, thus preventing DNA denaturation and induction of conformational alterations responsible for genetic instability. DNA topoisomerase I in vivo cleaves the (TTA)35 sequence after nucleosome removal, the positioned nucleosome on the (TTA)35 sequence represents a hindrance to the DNA topoisomerase I activity. This last conclusion, based on the glucose/galactose experiments, represents the first formal evidence that DNA topoisomerase I cannot react with nucleosomal DNA
-
-
?
117-base pair DNA oligonucleotide
?
-
-
-
-
?
DNA
DNA
-
so-called suicide substrate, contains a htopoI preferential binding sequence and is designed to trap the liberated 5'-OH end
-
-
?
Holliday Junction Substrate H1-4
?
-
close relationship between tyrosine recombinases and type IB topoisomerases, investigation of ability of human topoisomerase I to resolve the typical intermediate of recombinase catalysis, the Holliday junction, results consolidate the relationship between type IB topoisomerases and tyrosine recombinases
-
-
?
negatively supercoiled DNA
?
negatively supercoiled DNA
relaxed DNA
negatively supercoiled pBlueScript KSII(+) DNA
relaxed pBlueScript KSII(+) DNA
-
-
-
?
negatively supercoiled pHC624 plasmid DNA
relaxed pHC624 plasmid DNA
-
-
-
-
?
negatively supercoiled pHOTI plasmid DNA
?
-
-
-
?
negatively supercoiled plasmid pXXZ06 DNA
?
-
-
-
-
?
negatively supercoiled PUC18 DNA
?
-
unable to relax positively supercoiled DNA
-
?
Nicked circular DNA
Large catenated DNA networks
relaxed pBR322 DNA
?
-
-
-
-
?
SF2/ASF protein + ATP
?
-
kinase activity
-
?
supercoiled DNA
relaxed closed circular DNA
supercoiled DNA
relaxed DNA
supercoiled pBAD/Thio plasmid DNA
relaxced pBAD/Thio plasmid DNA
-
-
-
-
?
supercoiled pBR322 DNA
?
-
-
-
-
?
supercoiled pBR322 plasmid DNA
relaxed pBR322 plasmid DNA
supercoiled plasmid DNA pBR322
relaxed plasmid DNA pBR322
-
-
-
?
supercoiled plasmid DNA pGEM-5T
?
-
relaxation
-
?
supercoiled plasmid pBAD-GFPuv
?
supercoiled plasmid pBR322 DNA
relaxed plasmid pBR322 DNA
-
-
-
-
?
additional information
?
-
DNA
?
-
specific for single-stranded DNA, the enzyme drives extensive unwinding of closed circular DNA at high temperature. At 60-80°C it relaxes negatively but not positively supercoiled DNA. At 95°C, the enzyme unwinds both positively and negatively supercoiled substrates and produces extensively unwound form I* and I** DNA
-
-
?
DNA
?
-
specific for single-stranded DNA, the enzyme drives extensive unwinding of closed circular DNA at high temperature. At 60-80°C it relaxes negatively but not positively supercoiled DNA. At 95°C, the enzyme unwinds both positively and negatively supercoiled substrates and produces extensively unwound form I* and I** DNA
-
-
?
DNA
?
the enzyme exhibits a very high DNA relaxing activity. Strong preference for a cytosine at position -4 of the cleavage
-
-
?
DNA
?
the enzyme exhibits a very high DNA relaxing activity. Strong preference for a cytosine at position -4 of the cleavage
-
-
?
negatively supercoiled DNA
?
-
-
?
negatively supercoiled DNA
?
-
-
-
?
negatively supercoiled DNA
?
-
-
-
?
negatively supercoiled DNA
?
-
the activity of the protein in supercoil removal is limited and biphasic: in the first phase it progressively changes the linking-number of hypernegatively supercoiled DNA, but only to the superhelicity of a regular negative supercoil, in the second phase the enzyme relaxes the DNA further, but only slightly and slowly. The C-terminal 334 amino acids are unnecessary for activity, suggesting that this region, and perhaps the entire protein is involved in a function other than supercoil removal
-
?
negatively supercoiled DNA
?
-
the enzyme relaxes negatively supercoiled DNA in a distributive manner, leading to the total disappearance of the initial substrate and the appearance of intermediate topoisomers. The enzyme is able to cleave a single stranded oligonucleotide to bind covalently to the 5-end of cleaved DNA. The consensus sequence for DNA cleavage is CANNN-/-
-
?
negatively supercoiled DNA
?
-
ATP-independent relaxation of negatively supercoiled DNA. The lack of stimulation by ssDNA binding protein SSB suggests that ssDNA regions required for SsTop3 binding are stably exposed in the negatively supercoiled substrate at the high reaction temperature, even in the absence of ssDNA binding protein SSB
-
-
?
negatively supercoiled DNA
?
-
-
-
?
negatively supercoiled DNA
relaxed DNA
-
-
-
-
?
negatively supercoiled DNA
relaxed DNA
-
-
-
-
?
negatively supercoiled DNA
relaxed DNA
-
-
-
?
negatively supercoiled DNA
relaxed DNA
-
-
-
-
?
negatively supercoiled DNA
relaxed DNA
-
TopR1 can relax negative supercoils without ATP, while the extent of positive supercoiling catalyzed by TopR1 is dependent on the stoichiometry, the ATP concentration, the NaCl concentration and the assay temperature
-
-
?
Nicked circular DNA
Large catenated DNA networks
-
enzyme catalyzes: 1. linking or intertwining of covalently closed single-stranded DNA rings containing complementary base sequences, 2. formation of topological knots in single-stranded DNA rings, 3. catenation and decatenation of double-stranded DNA circles, if one of the reacting DNA molecules has a nick
-
-
?
Nicked circular DNA
Large catenated DNA networks
-
-
-
-
?
Nicked circular DNA
Large catenated DNA networks
-
catenation reaction
-
-
?
Nicked circular DNA
Large catenated DNA networks
-
-
-
-
?
Nicked circular DNA
Large catenated DNA networks
-
pBR322 DNA
-
-
?
Nicked circular DNA
Large catenated DNA networks
-
catenation reaction
-
-
?
Nicked circular DNA
Large catenated DNA networks
-
ColE1 DNA
which appear to rearrange to multimeric linear structures upon long incubation time
?
Nicked circular DNA
Large catenated DNA networks
-
catenation reaction
which appear to rearrange to multimeric linear structures upon long incubation time
?
supercoiled DNA
?
-
the enzyme relaxes supercoiled DNA starting from a certain point in the DNA molecules and proceeds in one direction towards one of the edges of the DNA molecule. The relaxation of the supercoiled DNA is subsequently followed by a knotting event
-
?
supercoiled DNA
?
-
reverse gyrase induces unwinding of synthetic four-way junctions as well as forked DNA substrates, following a mechanism independent of both the ATPase and the strand cutting activity of the enzyme. Reverse gyrase works like an ATP-independent helix-destabilizing protein specific for branched DNA structures
-
-
?
supercoiled DNA
?
-
reverse gyrase induces unwinding of synthetic four-way junctions as well as forked DNA substrates, following a mechanism independent of both the ATPase and the strand cutting activity of the enzyme. Reverse gyrase works like an ATP-independent helix-destabilizing protein specific for branched DNA structures
-
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
removes superhelical turns from a negatively twisted DNA, no effect on positive superhelical turns
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
ColE1 DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
removes both positive and negative supercoils in steps of one
-
?
supercoiled DNA
relaxed closed circular DNA
-
pBR322 DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
Drosophila sp. (in: flies)
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
Drosophila sp. (in: flies)
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
Drosophila sp. (in: flies)
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
Drosophila sp. (in: flies)
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
Drosophila sp. (in: flies)
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
Drosophila sp. (in: flies)
-
pBR322 DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
rather weak sequence specificity
-
?
supercoiled DNA
relaxed closed circular DNA
-
single-strand of DNA double helix
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation of both negatively and positively supercoiled DNA circles
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
pBR322 DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
specific for negatively supercoiled DNA, no activity with positively supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
cleavage sites on pNSI DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
rather weak sequence specificity
-
?
supercoiled DNA
relaxed closed circular DNA
-
negatively supercoiled plasmid pBR322 DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
negatively supercoiled plasmid pUC9 DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
negatively supercoiled plasmid pUC9 DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
negatively supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
negatively supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
negatively supercoiled plasmid DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
pBR322 DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
rather weak sequence specificity
-
?
supercoiled DNA
relaxed closed circular DNA
-
single-strand of DNA double helix
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
enzyme links to the 3' ends of the broken DNA strands
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
enzyme cannot rewind relaxed closed circular DNA
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
enzyme cannot rewind relaxed closed circular DNA
?
supercoiled DNA
relaxed closed circular DNA
-
ColE1 DNA
enzyme cannot rewind relaxed closed circular DNA
?
supercoiled DNA
relaxed closed circular DNA
salmon
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
rather weak sequence specificity
-
?
supercoiled DNA
relaxed closed circular DNA
-
when oligonucleotide DNA duplexes are used as substrates, the generated cleavage complex contains an active enzyme, which is able to ligate the cleaved DNA to a variety of DNA fragments containing a free 5'-OH end
-
?
supercoiled DNA
relaxed closed circular DNA
-
single-strand of DNA double helix
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
positive and negative supercoiled DNA
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed closed circular DNA
-
relaxation
-
?
supercoiled DNA
relaxed DNA
the enzyme relaxes the negative DNA supercoiling generated by RNA polymerase during transcription elongation
-
-
?
supercoiled DNA
relaxed DNA
-
-
-
-
?
supercoiled pBR322 plasmid DNA
relaxed pBR322 plasmid DNA
-
-
-
-
?
supercoiled pBR322 plasmid DNA
relaxed pBR322 plasmid DNA
-
-
-
?
supercoiled plasmid pBAD-GFPuv
?
-
-
-
-
?
supercoiled plasmid pBAD-GFPuv
?
-
-
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
role in control of DNA topology including regulation of supercoiling and maintenance of genetic stability
-
-
?
additional information
?
-
-
no decatenation activity
-
-
?
additional information
?
-
-
enzyme controls repair function
-
-
?
additional information
?
-
-
topoisomerase I works in concert with topoisomerase II to modulate the level of DNA supercoiling
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
DNA relaxation using supercoiled plasmid DNA pBR322 or pRYG
-
-
?
additional information
?
-
when enzyme expression is interfered with by a cognate double-stranded RNA injection, pleiotropic phenotypes with abnormalities in germ cell proliferation, oogenesis and embryogenesis appeare
-
?
additional information
?
-
-
when enzyme expression is interfered with by a cognate double-stranded RNA injection, pleiotropic phenotypes with abnormalities in germ cell proliferation, oogenesis and embryogenesis appeare
-
?
additional information
?
-
-
substrate is supercoiled pUC19 plasmid DNA. The enzyme contains a secondary DNA binding site located on the surface of the C-terminal domain, site architecture, overview. DNA binding mechanism and implications for TopIB-mediated DNA synapsis, modelling, detailed overview
-
-
?
additional information
?
-
Drosophila sp. (in: flies)
-
-
-
-
?
additional information
?
-
Drosophila sp. (in: flies)
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
catalyzes the conversion of a paranemic to aplectonemic joint
-
-
?
additional information
?
-
-
enzyme catalyzes: 1. linking or intertwining of covalently closed single-stranded DNA rings containing complementary base sequences, 2. formation of topological knots in single-stranded DNA rings
-
-
?
additional information
?
-
-
phosphoryltosyl linkage between DNA and enzyme
-
-
?
additional information
?
-
-
site-specific binding to DNA substrate, enzyme linkage to 5'-ends of DNA
-
-
?
additional information
?
-
enzyme changes conformation dramatically during the reaction cycle in order to accomplish these transformations. A 30000 Da fragment moves away from the rest of the protein to create an entrance into the central whole in the protein. This fragment can change conformation significantly. The fragment is composed of two domains, and while the domains themselves remain largely unchanged, their relative arrangement can change dramatically
-
?
additional information
?
-
-
enzyme changes conformation dramatically during the reaction cycle in order to accomplish these transformations. A 30000 Da fragment moves away from the rest of the protein to create an entrance into the central whole in the protein. This fragment can change conformation significantly. The fragment is composed of two domains, and while the domains themselves remain largely unchanged, their relative arrangement can change dramatically
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
substrate is negatively supercoiled DNA
-
-
?
additional information
?
-
-
the enzyme structure with bound DNA shows distinct conformational changes from the structure of the enzyme without bound DNA, overview. The portion of cleaved DNA 5' to the site of cleavage is anchored tightly with extensive noncovalent protein-DNA interactions. The portion of the oligonucleotide 5' to the cleavage site binds in a deep groove formed at the interface of domains I and III as well as within domain IV, in a similar orientation. Residues R195 and R321 are required for DNA cleavage
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-
?
additional information
?
-
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the strictly conserved arginine residue proximal to the active site tyrosine of type IA topoisomerases is required for the relaxation of supercoiled DNA. DNA cleavage can still take place in the absence of Arg231 function if Mg2+ is present to enhance the interaction of the enzyme with the scissile phosphate, but DNA rejoining is inhibited in the absence of this conserved arginine, resulting in accumulation of the cleaved covalent intermediate and loss of relaxation activity. In addition to the divalent metal ions, the side chain of this arginine residue is required for the precise positioning of the phosphotyrosine linkage for nucleophilic attack by the 3'-OH end to result in DNA rejoining
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?
additional information
?
-
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cleavage of 556 base single-stranded DNA substrate supercoiled pBAD/thio plasmid, and cleavage and religation of 59 base hairpin oligonucleotide substrates
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?
additional information
?
-
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relaxation and cleavage of pBR322 DNA, differences in the mechanism of these two related type IA topoisomerases, Topo I and Topo III, overview
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?
additional information
?
-
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single-molecule DNA relaxation assay, the pauses of the enzyme are short and the relaxation runs are slow
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?
additional information
?
-
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topoisomerase I cleaves and rejoins one strand of double-stranded DNA to relax the negatively supercoiled DNA
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?
additional information
?
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additional information
?
-
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recognizes DNA in a nonrandom fashion
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?
additional information
?
-
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a novel type of reaction is detected in the course of which an enzyme-attached single-stranded fragment is transferred and covalently ligated to the 5'-end of a separate double-stranded DNA molecule
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?
additional information
?
-
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enzyme promotes intertwining of complementary single-stranded DNA circles by forming relaxed duplex circles covalently closed in both strands. If denatured supercoiled PM2-DNA is used as a substrate, relaxed duplex circles as well as highly knotted molecules are seen among the products
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?
additional information
?
-
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enzyme becomes covalently linked to the 3'-phosphoryl group, when it cleaves DNA
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?
additional information
?
-
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may participate in recombination events
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?
additional information
?
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provides a swivel during replication
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?
additional information
?
-
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controls the DNA topology by cleaving and rejoining DNA strands and passing other DNA strands through the transient gaps, plays a crucial role in the regulation of the physiological function of the genome
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?
additional information
?
-
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probably engaged in the assembly of chromatin
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?
additional information
?
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enzyme controls the topological state of DNA
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?
additional information
?
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plays a role in transcriptional elongation
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?
additional information
?
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plays a crucial role in controlling the physiological functions of DNA
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?
additional information
?
-
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plays a direct role in the regulation of transcriptional initiation by acting as a repressor of the basal-level transcription
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?
additional information
?
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role of topoisomerase I in DNA replication, transcription and recombination
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?
additional information
?
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enzyme is unable to resolve topologically knotted circular duplex DNA
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?
additional information
?
-
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covalently binds double-stranded and single-stranded DNA forming an enzyme linked to the 3'-phosphoryl end and after binding to single-stranded DNA it can transfer the single-stranded donor DNA to an acceptor DNA possessing 5'-OH end groups
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?
additional information
?
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enzyme controls the topological state of DNA
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?
additional information
?
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-
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?
additional information
?
-
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-
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?
additional information
?
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enzyme breaks down single-stranded DNA to smaller fragments. Each cleavage generates a free 5'-OH end and an enzyme-linked 3'-phosphoryl end
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?
additional information
?
-
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DNA structural alterations induced by UV lesions can be sufficient stimulus to induce cross-linking of topoisomerase I to cellular DNA
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?
additional information
?
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enzyme controls the topological state of DNA
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-
?
additional information
?
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enzyme controls the topological state of DNA
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?
additional information
?
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Topo I is the first endogenous interaction partner for c-Jun in the regulation of cancer cell proliferation. Topo I and JNK-c Jun pathway cooperate in the regulation of eGFR gene expression and in the proliferation of HT-1080 cells
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?
additional information
?
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only enzyme forms containing amino acids 203-765 can accurately control all steps of catalysis, particularly the DNA strand cleavage and the proposed controlled rotation relaxation of DNA supercoils
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?
additional information
?
-
structure-activity relationship, overview
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?
additional information
?
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Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor, TF, via phosphorylation of serine/arginine-rich proteins. Selective inhibition of Cdc2-like kinases and DNA topoisomerase I elicite distinct changes in TF biosynthesis in TNF-alpha-stimulated endothelial cells, which impact endothelial procoagulant activity, overview
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-
?
additional information
?
-
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DNA topoisomerase IB catalyzes the relaxation of supercoiled DNA through the transient cleavage of one strand of a DNA duplex, molecular dynamics simulation of wild-type and mutant K681A enzymes, the N-terminal and C-terminal regions of the core domain show a slightly larger and a slightly smaller displacements, respectively, in the wild type than in the mutant enzyme, overview
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?
additional information
?
-
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human cells can rapidly activate and deactivate DNA topoisomerase I in response to a signal molecule, the activity of DNA topoisomerase I is highly regulated in HuT 78 cells upon treatment with interleukin-2, overview
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?
additional information
?
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reversible reaction. TopI produces a single strand break in DNA, allowing relaxation of DNA during its replication. The single strand break is then religated, thus restoring the DNA double strands. The enzymatic mechanism involves two sequential transesterification reactions. The cleavage reaction involves the active site Tyr723 acting as a nucleophile. A phenolic oxygen attacks a DNA phosphodiester bond, forming an intermediate in which the 3' end of the broken strand is covalently attached by an O4-phosphodiester bond to TopI tyrosine. The religation step consists of transesterification involving a nucleophilic attack by the hydroxyl oxygen at the 5' end of the broken strand. The equilibrium constant of the breakage and closure reactions is close to unity
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?
additional information
?
-
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Top1 functionally interacts with splicing factor ASF/SF2, alternative splicing factor/splicing factor 2 modulating its the function to prevent genomic instability in S phase
-
-
?
additional information
?
-
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cleavage of oligonucleotide substrates 5'-GAAAAAAGACTTAG-3' and 5'-TAAAAATTTTTCTAAGTCTTTTTTC-3'. Crucial role for the linker domain and occurrence of a long range communication between the linker and the active site region, overview
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?
additional information
?
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substrate is pBR322 DNA, structure-activity relationship study, overview
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?
additional information
?
-
-
substrate is pBR322 or pHC624 supercoiled DNA
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-
?
additional information
?
-
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substrate is supercoiled pBR322 DNA
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?
additional information
?
-
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substrate is supercoiled pBR322 DNA
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?
additional information
?
-
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substrate is supercoiled pBR322 DNA
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?
additional information
?
-
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substrate is supercoiled plasmid pSP73KB DNA, a multiple metallation of the short nucleotide sequences on the scissile strand, immediately downstream of the cleavage site impedes the cleavage by top1. Top1-mediated cleavage of a 30-bp oligonucleotide duplex
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?
additional information
?
-
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substrate is superhelical DNA in plasmid supercoiled pBR322, with deoxy-nucleotides, relaxation
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?
additional information
?
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Top1 relaxes supercoiled structures in DNA, thus creating a nick. Top1 cleaves a phosphodiester bond near the 3' end of the nick and forms a covalent bond with the 3' end of the newly formed break. This process involves the catalytic tyrosine residue necessary for nucleophilic attack and disruption of a phosphodiester bond in DNA. and it involves poly(ADP-ribose) polymerase 1, that phosphoribosylates the enzyme and affect binding to DNA, overview. Interaction of human recombinant DNA topoisomerase 1 with linear and circular DNA structures containing a nick or short gap but lacking a specific Top1 recognition site, using circular M13mp19 phage DNA and the 34mer DNA duplex containing uracil in position 16 of one of the duplex strands (U-G) as substrate. Partial inhibition of the Top1-DNAadduct formation upon addition of poly(ADP ribose) polymerase 1 in the absence of NAD+ is shown, whereas in the presence of NAD+ formation of a high molecular weight product, most likely corresponding to poly(ADP) ribosylated Top1-DNA adduct, is observed. Top1 covalent adducts with DNA containing a singlestranded break or a short gap in the absence of a recognition site are also formed with involvement of the catalytic tyrosine residue in the enzyme active center
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?
additional information
?
-
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TopI catalyzes supercoiled plasmid DNA relaxation
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?
additional information
?
-
Topo I catalyses two distinct reactions, the DNA relaxation and the phosphorylation of serine/arginine motifs which are present in essential splicing factors in a mutually exclusive manner, structure-function relationship, molecular dynamics modelling, overview
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?
additional information
?
-
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Topo I catalyses two distinct reactions, the DNA relaxation and the phosphorylation of serine/arginine motifs which are present in essential splicing factors in a mutually exclusive manner, structure-function relationship, molecular dynamics modelling, overview
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-
?
additional information
?
-
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cleavage of supercoiled DNA by topoisomerase I
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?
additional information
?
-
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relaxation of supercoiled pBR322 plasmid DNA
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?
additional information
?
-
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substrate for DNA topo I is pBR322 plasmid DNA
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?
additional information
?
-
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substrate for DNA topo I is supercoiled pBR322 plasmid DNA
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?
additional information
?
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substrate is negatively and positively supercoiled pBR322 DNA. Topoisomerase I removes positive superhelical twists about 10fold faster than it does negative superhelical twists
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?
additional information
?
-
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substrate is negatively supercoiled pBR322 plasmid DNA
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?
additional information
?
-
-
substrate is plasmid DNA
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?
additional information
?
-
-
substrate is supercoiled plasmid DNA
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?
additional information
?
-
-
usage of a 3'-end radiolabeled DNA substrate, a 117-bp DNA oligonucleotide
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?
additional information
?
-
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human topoisomerase I is a dual-activity enzyme. First, it transiently nicks double-stranded DNA. Next, topo I is a kinase that phosphorylates SR proteins, essential splicing factors, and regulators of splicing composed of one or two RNA recognition motifs (RRMs) followed by the RS domain (RS) and containing numerous serine-arginine repeats. Topo I is one of several protein kinases that phosphorylate SR proteins, enzymes of both families, SRPK1 and CLK1
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?
additional information
?
-
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the enzyme catalyzes the relaxation of supercoiled DNA during DNA replication and transcription
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?
additional information
?
-
-
enzyme substrates are S(hTopI)Id16, S(PosC)Id33, and fluorescently labeled detection oligonucleotides ID16-TAMRA and ID33-6FAM
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-
?
additional information
?
-
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substrate is supercoiled plasmid DNA, and oligonucleotide substrate CL14 , 5'-GAAAAAAGACTTAG-3', annealed with CP25 complementary strand (5'-TAAAAATTTTTCTAAGTCTTTTTTC-3)', that is 5'-phosphorylated with unlabelled ATP
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?
additional information
?
-
the enzyme recruits Sir2p to the rDNA
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?
additional information
?
-
-
the enzyme recruits Sir2p to the rDNA
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?
additional information
?
-
-
DNA binding and subunit interaction analysis of wild-type and mutant enzymes, overview
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-
?
additional information
?
-
TopIIIbeta possesses a weak, ATP-independent relaxation activity towards negatively supercoiled DNA only
-
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?
additional information
?
-
-
TopIIIbeta possesses a weak, ATP-independent relaxation activity towards negatively supercoiled DNA only
-
-
?
additional information
?
-
the active site tyrosine is located at the 327 position within a highly conserved GYISYPRTES sequence
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-
?
additional information
?
-
-
the active site tyrosine is located at the 327 position within a highly conserved GYISYPRTES sequence
-
-
?
additional information
?
-
TopIIIbeta possesses a weak, ATP-independent relaxation activity towards negatively supercoiled DNA only
-
-
?
additional information
?
-
the active site tyrosine is located at the 327 position within a highly conserved GYISYPRTES sequence
-
-
?
additional information
?
-
-
the enzyme has at least two different active centers capable of processing apurinic/apyrimidinic site DNA
-
?
additional information
?
-
-
the topoisomerase and DNA repair activities reside in different parts of the protein and the DNA repair activity is dispensable for the topoisomerase catalytic activity
-
?
additional information
?
-
-
topo V contains a signature motif of leucine-responsive regulatory proteins and therefore might also act as a transcriptional regulator, in addition to being a topoisomerase and an apurinic/apyrimidinic lyase
-
?
additional information
?
-
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-
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?
additional information
?
-
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enzyme controls the topological state of DNA
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-
?
additional information
?
-
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-
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?
additional information
?
-
-
enzyme controls the topological state of DNA
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?
additional information
?
-
-
mapping cleavage sites on single-stranded DNA substrate Mtop with length of 216 bases amplified from topA gene of Mycobacterium tuberculosis, substrate is negatively supercoiled DNA
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?
additional information
?
-
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
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-
?
additional information
?
-
-
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
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?
additional information
?
-
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topoisomerase I shows a negative interplay between MazF protein Rv1495. Through its C-terminal domain, MtbTopA physically interacts with and inhibits the mRNA cleavage activity of Rv1495, overview. Rv1495, in turn, inhibits the DNA cleavage activity of MtbTopA as well as its function of relaxation of supercoiled DNA
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-
?
additional information
?
-
-
structure-function analysis of MtTOP1, overview
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?
additional information
?
-
substrate is supercoiled plasmid DNA
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?
additional information
?
-
-
substrate is supercoiled plasmid DNA
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?
additional information
?
-
enzyme activity on relaxation of supercoiled pUC18 DNA or on 5' end labeled oligonucleotides having the strong topoisomerase I site, the enzyme cleaves DNA at preferred sites in a pattern similar to its ortholog from Mycobacterium smegmatis
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?
additional information
?
-
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enzyme activity on relaxation of supercoiled pUC18 DNA or on 5' end labeled oligonucleotides having the strong topoisomerase I site, the enzyme cleaves DNA at preferred sites in a pattern similar to its ortholog from Mycobacterium smegmatis
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?
additional information
?
-
enzyme activity on relaxation of supercoiled pUC18 DNA or on 5' end labeled oligonucleotides having the strong topoisomerase I site, the enzyme cleaves DNA at preferred sites in a pattern similar to its ortholog from Mycobacterium smegmatis
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?
additional information
?
-
the mycobacterial topoisomerase I physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
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-
?
additional information
?
-
substrate is supercoiled plasmid DNA
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?
additional information
?
-
-
MsTopA stimulates the phosphorylating activity of Ms3759 on D-ribose, and physically interacts with its ribokinase both in vitro and in vivo with opposite effects on their respective function, overview. Interaction analysis, overview
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-
?
additional information
?
-
-
topoisomerase I shows a negative interplay between MazF protein Rv1495. Through its C-terminal domain, MsTopA physically interacts with and inhibits the mRNA cleavage activity of Rv1495. Rv1495, in turn, inhibits the DNA cleavage activity of MsTopA as well as its function of relaxation of supercoiled DNA
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?
additional information
?
-
-
substrate is supercoiled plasmid DNA
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?
additional information
?
-
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MstopoI carries out the DNA relaxation reaction in a processive fashion
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?
additional information
?
-
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DNA cleavage assay using a 32-mer oligonucleotide harboring strong topoI sites to yield a 5'-end-labeled 19-mer cleavage product. For intramolecular religation, 32-mer oligonucleotide harboring strong topoI sites is incubated with wild-type or deletants to yield a noncovalenty held 19-mer and 13-mer covalent protein-DNA adduct
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?
additional information
?
-
-
enzyme controls the topological state of DNA
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-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
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-
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?
additional information
?
-
-
catalyzes catenene formation, a reaction specific for type II topoisomerase
-
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?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
topoisomerase I forms in vivo complexes with DNA substrates, the complexes are stabilized by irinotecan, which has DNA strand breaking ability, it leads to topisomerase poisoning and DNA damage, overview
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?
additional information
?
-
-
wild-type enzyme and mutant enzyme N726H exhibit a distinctively processive mode of plasmid relaxation, mutant enzyme N726D exhibits a distributive mode of plasmid DNA relaxation
-
?
additional information
?
-
-
FOB1 affects DNA topoisomerase I in vivo cleavages in the enhancer region of the Saccharomyces cerevisiae ribosomal DNA locus. Binding to DNA of Fob1p itself may be the cause of the DNA topoisomerase I activity in the rDNA enhancer
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?
additional information
?
-
-
H2O2 induces topoisomerase I-mediated DNA damage and cell death. H2O2 promotes the trapping of topoisomerase I on oxidative DNA lesions to form TOP1-DNA cleavage complexes that contribute to H2O2 toxicity
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?
additional information
?
-
-
the enzyme recruits Sir2p to the rDNA
-
-
?
additional information
?
-
-
the enzyme recruits Sir2p to the rDNA
-
-
?
additional information
?
-
salmon
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
Sau-TopoI enzyme converts negatively supercoiled form I DNA to relaxed form II DNA in ATP-independent and Mg2+-dependent manners. Cleavage site mapping shows that the enzyme preferentially binds to and cleaves the sequence GGNN-/-CAT, with N and -/- representing any nucleotide and cleavage site, respectively
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?
additional information
?
-
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Sau-TopoI enzyme converts negatively supercoiled form I DNA to relaxed form II DNA in ATP-independent and Mg2+-dependent manners. Cleavage site mapping shows that the enzyme preferentially binds to and cleaves the sequence GGNN-/-CAT, with N and -/- representing any nucleotide and cleavage site, respectively
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-
?
additional information
?
-
Sau-TopoI enzyme converts negatively supercoiled form I DNA to relaxed form II DNA in ATP-independent and Mg2+-dependent manners. Cleavage site mapping shows that the enzyme preferentially binds to and cleaves the sequence GGNN-/-CAT, with N and -/- representing any nucleotide and cleavage site, respectively
-
-
?
additional information
?
-
-
enzyme exhibits highly efficient reverse transcriptase activity in addition to their predicted functions
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-
?
additional information
?
-
-
substrate is pUC19 plasmid DNA, and for supercoiling assay substrate pWHM3 plasmid DNA
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-
?
additional information
?
-
-
enzyme exhibits highly efficient reverse transcriptase activity in addition to their predicted functions
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-
?
additional information
?
-
-
catalyzes the conversion of a paranemic to aplectonemic joint
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-
?
additional information
?
-
-
enzyme makes a single strand break and forms a covalent bond through the 3'-end of the broken strand
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
Arg130 forms electrostatic interactions with both nonbridging oxygen and the 5'-leaving group
-
-
?
additional information
?
-
-
remote phosphate contacts trigger assembly of the active site of DNA topoisomerase IB
-
-
?
additional information
?
-
-
the vaccinia type I DNA topoisomerase exhibits a strong site-specific ribonuclease activity when provided a DNA substrate that contains a single uridine ribonucleotide within a duplex DNA containing the sequence 5'CCCTU3'. The reaction involves two steps: attack of the active site tyrosine nucleophile followed by nucleophilic attack of the uridine 2'-hydroxyl to release the covalently tethered enzyme
-
-
?
additional information
?
-
-
when Vaccinia topoisomerase I is present with relaxed DNA in the presence of enrofloxacin (inhibitor of relaxation activity), it executes the reverse reaction, supercoiling the DNA
-
-
?
additional information
?
-
-
type I DNA topoisomerase from vaccinia virus, vTopo, forms a reversible covalent 3'-phosphotyrosyl linkage with a single strand of duplex DNA at the preferred sequence 5'-(C/T) CCTTp-/-N-1N-2N-3-3'. Site-specific DNA cleavage and ligation chemistry. Oscillation between an open and closed state of the covalently bound enzyme is likely important for regulating the number of DNA superhelical turns that are removed during the lifetime of the covalent complex with supercoiled substrates
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-
?
additional information
?
-
-
-
-
-
?
additional information
?
-
-
enzyme controls the topological state of DNA
-
-
?
additional information
?
-
-
the strictly conserved arginine residue proximal to the active site tyrosine of type IA topoisomerases is required for the relaxation of supercoiled DNA. DNA cleavage can still take place in the absence of Arg237 function if Mg2+ is present to enhance the interaction of the enzyme with the scissile phosphate, but DNA rejoining is inhibited in the absence of this conserved arginine, resulting in accumulation of the cleaved covalent intermediate and loss of relaxation activity. In addition to the divalent metal ions, the side chain of this arginine residue is required for the precise positioning of the phosphotyrosine linkage for nucleophilic attack by the 3'-OH end to result in DNA rejoining
-
-
?
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(+)-cheilanthifoline
-
very weak inhibition
(-)-cavidine
-
very weak inhibition
(-)-cryptotanshinone
-
diterpenoid from Salvia castanea f. tomentos
(-)-epigallocatechin
i.e. (2R,3R)-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3,5,7-triol
(-)-epigallocatechin 3-O-(E)-p-coumarate
-
(-)-epigallocatechin 3-O-(E)-p-coumaroate
-
(-)-epigallocatechin-3-gallate
-
(-)-epigallocatechin3-O-(Z)-p-coumarate
-
(-)-epigallocatechin3-O-(Z)-p-coumaroate
-
(-)-gallocatechin
i.e. (2R,3R)-3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)-2,3-dihydro-4H-1-benzopyran-4-one
(-)-pallidine
-
comparable to camptothecin
(-)-scoulerine
-
inhibition comparable to camptothecin
(-)-tetrahydropalmatine
-
very weak inhibition
(1,1',1'',1'''-[(1,4-dihydroporphyrin-5,10,15,20-tetrayl-k4N21,N22,N23,N24)tetrakis(benzene-4,1-diylmethanediyl)]tetrakis[1-methylpiperidiniumato(2-)])nickel(4+) tetraiodide
-
-
(1,1',1'',1'''-[(1,4-dihydroporphyrin-5,10,15,20-tetrayl-k4N21,N22,N23,N24)tetrakis(benzene-4,1-diylmethanediyl)]tetrakis[1-methylpiperidiniumato(2-)])zinc(4+) tetraiodide
-
-
(1-phenyl-ethylideneamino)-acetic acid
-
0.05 mM, 53% vTopo RNase activity remaining, 10% cTopo relaxation activity remaining
(1S,12aR,12bR)-1,4,9,12a-tetrahydroxy-1,2,11,12,12a,12b-hexahydroperylene-3,10-dione
i.e. altertoxin I
(1S,12S,12aR,12bR)-1,4,9,12,12a-pentahydroxy-1,2,11,12,12a,12b-hexahydroperylene-3,10-dione
i.e. 6-epi-stemphytriol
(2,2',2'',2''',2'''',2''''',2'''''',2'''''''-[(5,28-dihydro-29H,31H-tetrabenzoporphine-2,3,9,10,16,17,23,24-octayl-k4N29,N30,N31,N32)octasulfanediyl]octakis(N,N-diethyl-N-methylethanaminiumato)(2-))zinc(8+) octaiodide
-
-
(2-hydroxy-naphthalen-1-yl)-acetic acid
-
0.05 mM, 48% vTopo RNase activity remaining
(2E)-3-[(6R,7S)-7-[(2,4-dihydroxy-6-methylbenzoyl)oxy]-6-hydroxy-7-methyl-8-oxo-6,7,8,8a-tetrahydro-1H-2-benzopyran-3-yl]prop-2-enoic acid
i.e. pinophilin F
(2E)-3-[(7R)-7-[(2,4-dihydroxy-6-methylbenzoyl)oxy]-7-methyl-6,8-dioxo-6,7,8,8a-tetrahydro-1H-2-benzopyran-3-yl]prop-2-enoic acid
i.e. (-)-mitorubrinic acid
(2R)-2-[(2S,3S)-3-acetamido-5-oxooxolan-2-yl]-2-hydroxy-N-[(S)-[(3S)-8-hydroxy-1-oxo-3,4-dihydro-1H-2-benzopyran-3-yl][(propan-2-yl)amino]methyl]acetamide (non-preferred name)
i.e. AI-77-C
(2S,3R)-5-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-8-phenyl-2,3,8,9-tetrahydro-10H-[1,4]dioxino[2,3-f]chromen-10-one
-
-
(2S,3R,4S,6R)-4-amino-2-methyl-6-((3-(2-phenyl-1-tosyl-1H-indol-3-yl)prop-2-yn-1-yl)oxy)tetrahydro-2H-pyran-3-ol
-
92.8% inhibition at 0.1 mM
(2S,3R,4S,6R)-4-amino-2-methyl-6-((3-(2-phenylbenzofuran-3-yl)prop-2-yn-1-yl)oxy)tetrahydro-2H-pyran-3-ol
-
25.5% inhibition at 0.1 mM
(2S,3R,4S,6R)-4-amino-2-methyl-6-((3-(2-phenylbenzo[b]thiophen-3-yl)prop-2-yn-1-yl)oxy)tetrahydro-2H-pyran-3-ol
-
32.2% inhibition at 0.1 mM
(2S,3R,4S,6R)-4-amino-2-methyl-6-(3-(2-phenyl-1H-indol-3-yl)prop-2-ynyloxy)tetrahydro-2H-pyran-3-ol
-
20.2% inhibition at 0.1 mM; 8.2% inhibition at 0.1 mM
(2S,3S,6R)-2-methyl-6-(3-(2-phenyl-1-tosyl-1H-indol-3-yl)prop-2-ynyloxy)tetrahydro-2H-pyran-3-amine
-
43.2% inhibition at 0.1 mM
(2S,3S,6R)-2-methyl-6-(3-(2-phenyl-1H-indol-3-yl)prop-2-ynyloxy)tetrahydro-2H-pyran-3-amine
-
4.0% inhibition at 0.1 mM
(2S,3S,6R)-2-methyl-6-(3-(2-phenylbenzo[b]thiophen-3-yl)prop-2-ynyloxy)tetrahydro-2H-pyran-3-amine
-
7.9% inhibition at 0.1 mM
(3-hydroxy-4-thiocyanato-benzylsulfanyl)-acetic acid
-
0.05 mM, 45% vTopo RNase activity remaining
(3beta,5alpha,6beta,17alpha,22E)-6-methoxyergost-22-ene-3,5-diol
i.e. 3beta,5alpha-dihydroxy-6beta-methoxy-ergosta-7,22-diene
(3beta,5alpha,6beta,17alpha,22E)-ergost-22-ene-3,5,6-triol
i.e. ergosta-7,22-diene-3beta,5alpha,6beta-triol
(3S,8aR)-3-[[(3S)-7,7-dimethyl-3-(2-methylbut-3-en-2-yl)-2-oxo-1,2,3,7-tetrahydropyrano[2,3-g]indol-3-yl]methyl]-8a-methoxyhexahydropyrrolo[1,2-a]pyrazine-1,4-dione
i.e. notoamide Q
(5aR,7R,9aR)-7',7',8,8-tetramethyl-1',2,3,7',8a,9-hexahydro-1H,2'H,5H,6H,8H,10H-spiro[5a,9a-(epiminomethano)cyclopenta[f]indolizine-7,3'-pyrano[2,3-g]indole]-2',5,10-trione
i.e. (-)-versicolamide B
(5aS,13bS)-1,5a,9,13-tetrahydroxy-3,7-dimethyl-5,5a-dihydro-4H,10H,12H,14H,16H-pyrano[3''',4''',5''':4'',5'']naphtho[2'',1'':4',5']furo[2',3':7,8]naphtho[1,8-cd]pyran-4,10,16-trione (non-preferred name)
i.e. bacillosporin C
(5Z,7E,9E,14Z,17Z)-icosa-5,7,9,14,17-pentaenoic acid
-
-
(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]-isoquinolin-3-yl)carbamic acid
-
-
(6aR,11aS)-11-[(4-methylphenyl)sulfonyl]-6,6a,11,11a-tetrahydro-5H-benzo[a]carbazole
(6bR,7aS,12aS,14aS)-6b-hydroxy-3,3-dimethyl-14a-(2-methylbut-3-en-2-yl)-3,6b,7,7a,10,11,12,12a,14a,15-decahydro-8H,13H-pyrano[2,3-g]pyrrolo[1'',2'':4',5']pyrazino[1',2':1,5]pyrrolo[2,3-b]indole-8,13-dione
i.e. notoamide D
(7aR,12aS)-5-methylidene-12-[(4-methylphenyl)sulfonyl]-7,7a,12,12a-tetrahydrobenzo[6,7]chromeno[4,3-b]indol-13(5H)-one
(7aS,12aS)-10-methoxy-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
(7aS,12aS)-11-methoxy-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carbaldehyde
(7aS,12aS)-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
(7aS,12aS,13aR)-3,3,14,14-tetramethyl-3,7,11,12,13,13a,14,15-octahydro-8H,10H-7a,12a-(epiminomethano)indolizino[6,7-h]pyrano[3,2-a]carbazole-8,16-dione
i.e. 6-epi-stephacidin A
(7aS,12aS,13aS)-3,3,14,14-tetramethyl-3,7,11,12,13,13a,14,15-octahydro-8H,10H-7a,12a-(epiminomethano)indolizino[6,7-h]pyrano[3,2-a]carbazole-8,16-dione
i.e. stephacidin A
(7R)-3-[(1E)-3-hydroxyprop-1-en-1-yl]-7-methyl-6,8-dioxo-6,7,8,8a-tetrahydro-1H-2-benzopyran-7-yl 2,4-dihydroxy-6-methylbenzoate
i.e. (-)-mitorubrinol
(7S,8S,8aS)-7-hydroxy-3-[(1E)-3-hydroxyprop-1-en-1-yl]-7-methyl-6-oxo-6,7,8,8a-tetrahydro-1H-2-benzopyran-8-yl 2,4-dihydroxy-6-methylbenzoate
i.e. pinophilin B
(7S,8S,8aS)-8-hydroxy-3-[(1E)-3-hydroxyprop-1-en-1-yl]-7-methyl-6-oxo-6,7,8,8a-tetrahydro-1H-2-benzopyran-7-yl 2,4-dihydroxy-6-methylbenzoate
i.e. pinophilin D
(9-([2-(1H-Indol-3-yl)ethyl]amino)-3-acridinyl)(4-methyl-1-piperazinyl)methanone
-
-
(9-([2-(1H-indol-3-yl)ethyl]amino)acridin-3-yl)(4-methylpiperazin-1-yl)methanone
-
-
(9-([2-(1H-indol-3-yl)ethyl]amino)acridin-4-yl)(4-methylpiperazin-1-yl)methanone
-
-
(9-[(1-benzylpiperidin-4-yl)amino]acridin-3-yl)(4-methylpiperazin-1-yl)methanone
-
-
(S)-6-(6-nitrobenzothiazol-2-yl)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine
-
-
(S)-6-(benzothiazol-2-yl)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-de][1,4]-benzoxazine
-
-
1,1',1'',1'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis(1-methylpiperidinium) tetraiodide
-
-
1,1',1'',1'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis[3-(ethoxycarbonyl)-1-methylpiperidinium] tetraiodide
-
-
1,1',1'',1'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis[3-(hydroxymethyl)-1-methylpiperidinium] tetraiodide
-
-
1,2'-binaphthalene-7',8-dicarboxylic acid
-
does not inhibit supercoil relaxation at 10 microM concentration. IC90 (compound concentration at which 90% or higher inhibition is observed) 2 microM, using high-throughput screen, relaxation inhibition 0%
1,3-bis(4-amino-2-methylquinolin-6-yl)urea
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 2 microM, using high-throughput screen, relaxation inhibition 40%
1,3-[6-(3-Amino-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline]-[5',6'-dihydro-6'-(3'-amino-1'-propyl)-5',11'-dioxo-11'H-indeno[1,2-c]-isoquinoline]propane bis(trifluoroacetate)
-
1,5-dideoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-xylo-hexitol
-
-
1-(3,4-dihydroxybenzyl)isoquinoline-6,7-diol
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 80%
1-(alpha-L-idopyranosyl)-N-(2-methylbenzoyl)-5-(methylsulfanyl)-1H-1,2,4-triazol-3-amine
-
-
1-(hydroxymethyl)-3-(2-hydroxypropan-2-yl)-2-(5-methoxy-9H-beta-carbolin-1-yl)-cyclopentanol
-
-
1-deoxy-1-(3-nitro-5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-glucitol
-
-
1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-allitol
-
-
1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-arabinitol
-
-
1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-galactitol
-
-
1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-glucitol
-
-
1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-mannitol
-
-
1-deoxy-1-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-ribitol
-
-
1-ethoxycarbonyl-naphthoquinone-[2,3-d]indolizidine-6,11-dione
-
0.1 mg/ml, 4.1% inhibition of relaxation
1-ethyl-3-(5-aminobenzimidazol-2-yl)-6-fluoro-7-(4-methyl-1-piperazinyl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-aminobenzoimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naph- thyridin-4(1H)-one
-
-
1-ethyl-3-(6-aminobenzoimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridin-4(1H)-one
-
-
1-ethyl-3-(6-aminobenzoimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-chlorobenzimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridine-4(1H)-one
-
-
1-ethyl-3-(6-chlorobenzimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzimidazol-2-yl)-6-fluoro-7-(4-methyl-1-piperazinyl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridine-4(1H)-one
-
-
1-ethyl-3-(6-nitrobenzimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzothiazol-2-yl)-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzothiazol-2-yl)-6-fluoro-7-(4-methylpiperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzothiazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridine-4(1H)-one
-
-
1-ethyl-3-(6-nitrobenzothiazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzoxazol-2-yl)-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4(1H)-quinolone
-
interacts with DNA-Top I complex and induces cancer cell apoptosis to produce antitumor effects, in vivo inhibition of anchorage-dependent colony formation
1-ethyl-3-(6-nitrobenzoxazol-2-yl)-6-fluoro-7-(4-methylpiperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(6-nitrobenzoxazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridine-4(1H)-one
-
-
1-ethyl-3-(6-nitrobenzoxazol-2-yl)-6-fluoro-7-chloro-4(1H)-quinolone
-
-
1-ethyl-3-(benzimidazol-2-yl)-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4(1H)-quinolone
-
9% and 11% inhibition at 0.1 mM and 0.02 mM, respectively
1-ethyl-3-(benzothiazol-2-yl)-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(benzothiazol-2-yl)-6-fluoro-7-(4-methylpiperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-3-(benzothiazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridine-4(1H)-one
-
-
1-ethyl-3-(benzothiazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-4(1H)-quinolone
-
-
1-ethyl-6,8-difluoro-7-(3-methylpiperazin-1-yl)-3-(6-nitro-1,3-benzoxazol-2-yl)quinolin-4(1H)-one
-
interacts with DNA-Top I complex and induces cancer cell apoptosis to produce antitumor effects
1-ethylKuQuinone
-
synthesis of the pentacyclic-diquinoid synthetic compound, overview. It efficiently inhibits the cleavage step of the enzyme reaction fitting well into the catalytic site. When incubated with the binary topoisomerase-DNA cleaved complex, the compound helps the enzyme to remove itself from the cleaved DNA and close the DNA gap, increasing the religation rate. Et-KuQ inhibits the relaxation activity of Top1. The compound also induces the religation of the stalled enzyme-camptothecin-DNA ternary complex. Docking and molecular modeling, overview
1-hydroxy-3-(oxiran-2-ylmethoxy)-9H-xanthen-9-one
-
-
1-hydroxy-3-[2-hydroxy-3-[(2-hydroxyethyl)amino]propoxy]-9H-xanthen-9-one
-
1.1% inhibition at 0.02 mM
1-hydroxy-3-[2-hydroxy-3-[(3-hydroxypropyl)amino]propoxy]-9H-xanthen-9-one
-
3.5% inhibition at 0.02 mM
1-hydroxy-8-methoxyanthracene-9,10-dione
-
-
1-methyl-3-(2-hydroxypropan-2-yl)-2-(5-methoxy-9H-beta-carbolin-1-yl)-cyclopentanol
-
-
1-[2-(dimethylamino)ethoxy]-8-methoxyanthracene-9,10-dione
-
-
1-[2-(dimethylamino)ethyl]-3-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]quinoxalin-2-amine
-
-
1-[3-[(dicyclohexylamino)methyl]-2,4-dihydroxyphenyl]ethanone
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 50%
10-methoxy-9-{2-[(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium-3-yl)oxy]ethoxy}[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium dichloride
-
synthetic protoberberine alkaloid, highly active
10-methoxy-9-{3-[(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium-3-yl)oxy]propoxy}[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium dichloride
-
synthetic protoberberine alkaloid, highly active
10-methoxy-9-{4-[(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium-3-yl)oxy]butoxy}[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium dichloride
-
synthetic protoberberine alkaloid, highly active
11-acetyl-10-amino-indolizino[3,2-g]quinoline-5,12-dione
-
-
11-acetyl-10-bromo-indolizino[3,2-g]quinoline-5,12-dione
-
-
11-acetyl-10-chloro-indolizino[3,2-g]quinoline-5,12-dione
-
-
11-acetyl-10-fluoro-indolizino[3,2-g]quinoline-5,12-dione
-
-
11-acetyl-10-hydroxy-indolizino[3,2-g]quinoline-5,12-dione
-
-
11-acetylindolizino[3,2-g]quinoline-5,12-dione
-
-
11-hexyl-5-(4-methylpiperazin-1-yl)-11H-indeno[1,2-c]isoquinolin-11-ol
-
-
11-hydroxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
-
-
11-hydroxy-2-methyl-8-nitro-4H-naphtho[2,3-h]chromene-4,7,12-trione
-
-
11-hydroxy-2-phenyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
-
-
11-hydroxy-3-[(1R)-1-hydroxy-3-methylbutyl]-4-methoxy-9-methyl-5H,7H-dibenzo[b,g][1,5]dioxocin-5-one
i.e. vermixocin A
11-methoxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
-
-
11-methoxy-2-phenyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
-
-
11-methyl-5-(4-methylpiperazin-1-yl)-11H-indeno[1,2-c]isoquinolin-11-ol
-
-
11-methylindolizino[3,2-g]quinoline-5,12-dione
-
-
11-[2-(dimethylamino)ethoxy]-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
-
-
12H-5,11a-diazadibenzo[b,h]fluoren-11-one
i.e. rosettacin
14-(1-imidazolylmethyl)-2H-5,11a-diazadibenzo[b,h]fluoren-11-one
-
14-(1-morpholinomethyl)-2H-5,11a-diazadibenzo[b,h]fluoren-11-one
-
14-(10'-aminodecyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(11'-aminoundecyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(12'-aminododecyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(2'-aminoethyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(3'-aminopropyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(3-aminopropyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one dihydrochloride
-
14-(3-N-ethanolaminopropyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trifluoroacetate
-
14-(4'-aminobutyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(5'-aminopentyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(6'-aminohexyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(7'-aminoheptyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(8'-aminooctyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(9'-aminononyl-1'-aminomethyl)-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trihydrochloride
-
14-(N,N-dimethylaminomethyl)-2H-5,11a-diazadibenzo[b,h]fluoren-11-one
-
14-(N-ethanolaminomethyl)-2H-5,11a-diazadibenzo[b,h]fluoren-11one
-
14-aminomethyl-12H-5,11a-diazadibenzo[b,h]fluoren-11-one dihydrochloride
-
14-chloromethyl-12H-5,11a-diazadibenzo[b,h]fluoren-11-one
-
14-chloromethyl-12H-5,11adiazadibenzo[b,h]fluoren-11-one
-
-
14-[(1-imidazolyl)propylaminomethyl]-12H-5,11a-diazadibenzo[b,h]fluoren-11-one
-
14-[1-(N-methylpiperazinylmethyl)]-2H-5,11a-diazadibenzo[b,h]fluoren-11-one
-
14-[3(1-morpholinopropyl)]-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trifluoroacetate
-
14-[3-(1-imidazolylpropyl)]-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trifluoroacetate
-
14-[3-(N,N-dimethylaminopropyl)]-12H-5,11a-diazadibenzo[b,h]fluoren-11-one trifluoroacetate
-
14-[N-(S)-3-hydroxypyrrolidinomethyl]-12H-5,11a diazadibenzo[b,h]fluoren-11-one
-
17-beta-3-oxo-18-norandrost-4-ene-17-carboxylic acid -4-bromo-benzene sulfonic acid ester
-
partial or complete inhibition of hTopo is only observed at relatively high compound concentrations in the range 5 to 20 microM
17-beta-3-oxo-18-Norandrost-4-ene-17-carboxylic acid-4-bromo-benzene sulfonic acid ester
-
shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 0.5 microM, using high-throughput screen, relaxation inhibition 50%
17beta-O-[N-(benzyl)carbomyl]-oleanolic acid
-
-
2'-(4-(3,6,9,12,15,18-hexaoxahenicos-20-ynyloxy)phenyl)-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzo[d]imidazole
2'-(4-ethoxyphenyl)-5-(4-methylpiperazinyl)-2,5'-bi-1H-benzimidazole
-
reversibly traps enzyme cleavage complexes with a different and more specific sequence selectivity
2'-(4-ethoxyphenyl)-6-(4-methylpiperazin-1-yl)-1H,3'H,2,5'-bisbenzimidazole
-
Hoechst 33342
2'-(4-hydroxyphenyl)-5-(4-methylpiperazinyl)-2,5'-bi-1H-benzimidazole
-
reversibly traps enzyme cleavage complexes with a different and more specific sequence selectivity
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
2'-[4-[(but-3-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
2'-[4-[(hex-5-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
2(2.6-dihydrobenzoyl)-3-hydroxy-5-hydroxymethylbenzoic acid methyl ester
-
2,2'-bis(8-formyl-1,6,7-trihydroxy-5-isopropyl-3-methylnaphthalene)
-
i.e. gossypol, belongs to the class II compounds which interfere with the catalytic function of topoisomerases without generating strand breaks
2,3-dichloro-5H-isoindolo[2,1-a]quinoxalin-6-one
-
-
2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
2,3-dimethoxy-8,9-methylenedioxy-10-(1H-imidazol-yl)methyl-11H-indeno[1,2-c]isoquinoline
-
2,3-dimethoxy-8,9-methylenedioxy-10-(4-methylpiperazin-1-yl)-methyl-11H-indeno[1,2-c]isoquinoline
-
2,3-dimethoxy-8,9-methylenedioxy-10-(4-morpholino)methyl-11H-indeno[1,2-c]isoquinoline
-
2,3-dimethoxy-8,9-methylenedioxy-10-(dimethylamino)methyl-11H-indeno[1,2-c]isoquinoline
influence of protonation state on Top1 inhibition
2,3-dimethoxy-8,9-methylenedioxy-10-(N,N',N'-trimethylethylenediamino)methyl-11H-indeno[1,2-c]isoquinoline
-
2,3-dimethoxy-8,9-methylenedioxy-10-(pyrrolidin-1-yl)methyl-11H-indeno[1,2-c]isoquinoline
influence of protonation state on Top1 inhibition
2,3-dimethoxy-8,9-methylenedioxy-10-methyl-11H-indeno[1,2-c]-isoquinoline
-
2,3-dimethyl-5H-isoindolo[2,1-a]quinoxalin-6-one
-
-
2,4-di(furan-2-yl)-5H-chromeno[4,3-b]pyridine
-
46.4% inhibition at 0.1 mM#
2,4-di(pyridin-2-yl)-5H-chromeno[4,3-b]pyridine
-
-
2,4-di(thiophen-2-yl)-5H-chromeno[4,3-b]pyridine
-
-
2,4-di(thiophen-3-yl)-5H-chromeno[4,3-b]pyridine
-
-
2,4-diphenyl-5H-chromeno[4,3-b]pyridine
-
-
2-((6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino)acetic acid
-
-
2-((6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino)acetic acid hydrochloride
-
-
2-(2-nitro-vinyl)-1H-indole
-
0.05 mM, 54% vTopo Rnase activity remaining
2-(4-((1-(2-azidoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
2-(4-(2-(4-(4-ethynylphenyl)-1H-1,2,3-triazol-1-yl)ethoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
2-(4-chlorobenzyl)benzoxazole
-
2-(4-chlorophenyl)-4-(furan-3-yl)-6-(3-methylthiophen-2-yl) pyridine
-
86% inhibition at 0.1 mM
2-(4-chlorophenyl)-6-(5-chlorothiophen-2-yl)-4-(furan-2-yl) pyridine
-
53% inhibition at 0.1 mM
2-(4-ethoxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]-imidazole
2-(4-hydroxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo-[d]imidazole-4-carboxylic acid
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
2-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-6-(5-methylfuran-2-yl) pyridine
-
13.2% inhibition at 0.1 mM
2-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-6-o-tolylpyridine
-
4.6% inhibition at 0.1 mM
2-(5-chlorothiophen-2-yl)-6-(furan-2-yl)-4-(furan-3-yl)pyridine
-
9.6% inhibition at 0.1 mM
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[2-methyl-1-(morpholin-4-ylcarbonyl)propyl]acetamide
-
-
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
-
-
2-(furan-2-carbonyl)-3-(pyridin-2-ylamino)-acrylonitrile
-
0.05 mM, 28% vTopo RNase activity remaining; 0.05 mM, 7% vTopo RNase activity remaining, 2% cTopo relaxation activity remaining
2-(furan-2-yl)-4-(furan-3-yl)-6-(3-methylthiophen-2-yl)pyridine
-
5.4% inhibition at 0.1 mM
2-(furan-2-yl)-4-(pyridin-2-yl)-5H-chromeno[4,3-b]pyridine
-
11.5% inhibition at 0.1 mM
2-(furan-2-yl)-4-(pyridin-3-yl)-5H-chromeno[4,3-b]pyridine
-
41.6% inhibition at 0.1 mM
2-(furan-2-yl)-4-(thiophen-2-yl)-5H-chromeno[4,3-b]pyridine
-
-
2-(furan-2-yl)-4-phenyl-5H-chromeno[4,3-b]pyridine
-
4.9% inhibition at 0.1 mM
2-(piperidin-1-yl)ethyl5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
2-(pyridin-2-yl)-4-(pyridin-3-yl)-5H-chromeno[4,3-b]pyridine
-
2.6% inhibition at 0.1 mM
2-(pyridin-2-yl)-4-(thiophen-2-yl)-5H-chromeno[4,3-b]pyridine
-
48.2% inhibition at 0.1 mM
2-(pyridin-2-yl)ethyl5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
2-(pyrrolidin-1-yl)ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
2-Amino-1-(1-benzyl-piperidin-4-yl)-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 4.1% inhibition of relaxation
2-Amino-1-(2-bromo-ethyl)-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 58.7% inhibition of relaxation
2-Amino-1-(2-hydroxy-ethyl)-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 27.3% inhibition of relaxation
2-Amino-1-(4-amino-phenyl)-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 9.4% inhibition of relaxation
2-Amino-1-(4-fluoro-phenyl)-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 67.8% inhibition of relaxation
2-Amino-1-benzyl-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 15.7% inhibition of relaxation
2-Amino-1-cyclohexyl-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 12.2% inhibition of relaxation
2-Amino-1-isopropyl-4,9-dioxo-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 8.6% inhibition of relaxation
2-amino-3-ethoxycarbonyl-N-(4-fluorophenyl)benz[f]indole-4,9-dione
-
potent inhibitor
2-amino-3-ethoxycarbonyl-N-methyl-benz[f]indole-4,9-dione
-
0.1 mg/ml, 5.6% inhibition of relaxation
2-Amino-4,9-dioxo-1-p-tolyl-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 4.3% inhibition of relaxation
2-Amino-4,9-dioxo-1-phenyl-3a,4,9,9a-tetrahydro-1H-benzo[f]indole-3-carboxylic acid ethyl ester
-
0.1 mg/ml, 2.9% inhibition of relaxation
2-bromoethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
2-hydroxy-3-ethoxycarbonyl-N-(3,4-dimethylphenyl)-benz[f]indole-4,9-dione
-
0.1 mg/ml, 6.6% inhibition of relaxation
2-methylidenebutanedioic acid
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 100%
2-O-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxyphenylacetic acid
-
2-phenoxymethylbenzimidazole
-
2-phenyl-4-(pyridin-2-yl)-5H-chromeno[4,3-b]pyridine
-
-
2-phenyl-4-(pyridin-3-yl)-5H-chromeno[4,3-b]pyridine
-
-
2-phenyl-4-(thiophen-2-yl)-5H-chromeno[4,3-b]pyridine
-
-
2-phenyl-4-(thiophen-3-yl)-5H-chromeno[4,3-b]pyridine
-
3.6% inhibition at 0.1 mM
2-pyridyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
The hypochromicity observed on DNA addition is too low for determination of binding constants
2-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-2-oxoacetic acid
-
-
2-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]-isoquinolin-3-yl)amino]acetic acid
-
-
2-[4-(2-azidoethoxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
2-[4-[(4,11-dihydroxy-5,10-dioxo-5,10-dihydro-1H-naphtho[2,3-f]indol-3-yl)methyl]piperazin-1-yl]ethyl acetate
-
-
2-[[2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl]oxy]-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromene-3,4,5,7-tetrol
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 0.5 microM, using high-throughput screen, relaxation inhibition 70%; IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%
20-mercaptocamptothecin
-
weak
20-thio camptothecin
-
analogue of camptothecin, inhibit a modified human topoisomerase I
3,10-dibromo-11-hydroxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
-
-
3,3'-(4-phenylpyridine-2,6-diyl)diphenol
-
67.2% inhibition at 0.1 mM
3,3'-diindolylmethane
-
(DIM) novel DNA topoisomerase I poison, which is a class I noncompetitive inhibitor, strongly inhibits Leishmania donovani topoisomerase I and stabilizes topoisomerase I-DNA cleavable complex
3,3'-[butane-1,4-diylbis(oxy)]bis(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium) dichloride
-
synthetic protoberberine alkaloid, highly active
3,3'-[ethane-1,2-diylbis(oxy)]bis(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium) dichloride
-
synthetic protoberberine alkaloid, highly active. Strongly stabilize the enzyme-DNA binary complex at low concentration (50100microM). From 0.1 to 1 mM, their ability to stabilize is weak
3,3'-[propane-1,3-diylbis(oxy)]bis(2,9,10-trimethoxy-5,6-dihydroisoquino[3,2-a]isoquinolinium) dichloride
-
synthetic protoberberine alkaloid, highly active
3,5-bis-dimethylaminomethyl-benzene-1,2-diol
-
0.05 mM, 52% vTopo RNase activity remaining, 30% cTopo relaxation activity remaining
3-(1,3-benzoxazol-2-yl)-1-ethyl-6-fluoro-7-(4-methylpiperazin-1-yl)quinolin-4(1H)-one
-
-
3-(1,3-benzoxazol-2-yl)-1-ethyl-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridin-4(1H)-one
-
-
3-(1,3-benzoxazol-2-yl)-7-chloro-1-ethyl-6,8-difluoroquinolin-4(1H)-one
-
-
3-(1,3-benzoxazol-2-yl)-7-chloro-1-ethyl-6-fluoroquinolin-4(1H)-one
-
-
3-(1H-benzimidazol-2-yl)-1-ethyl-6,8-difluoro-7-(3-methylpiperazin-1-yl)quinolin-4(1H)-one
-
-
3-(1H-benzimidazol-2-yl)-1-ethyl-6-fluoro-7-(4-methylpiperazin-1-yl)quinolin-4(1H)-one
-
-
3-(1H-benzimidazol-2-yl)-1-ethyl-6-fluoro-7-(piperazin-1-yl)-1,8-naphthyridin-4(1H)-one
-
-
3-(1H-benzimidazol-2-yl)-1-ethyl-6-fluoro-7-(piperazin-1-yl)quinolin-4(1H)-one
-
-
3-(2,3-dimethoxy-5,12-dioxo-5,12-dihydro-6H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinolin-6-yl)propan-1-aminium chloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
3-(2,6-diphenylpyridin-4-yl)phenol
-
11.5% inhibition at 0.1 mM
3-(2-phenyl-1-benzofuran-3-yl)prop-2-yn-1-yl 3-amino-2,3,6-trideoxy-b-D-arabino-hexopyranoside
-
77.8% inhibition at 0.1 mM
3-(2-phenyl-1-benzothiophen-3-yl)prop-2-yn-1-yl 3-amino-2,3,6-trideoxy-b-D-arabino-hexopyranoside
-
36.9% inhibition at 0.1 mM
3-(2-phenyl-1H-indol-3-yl)prop-2-yn-1-yl 3-amino-2,3,6-trideoxy-b-D-arabino-hexopyranoside
-
8.8% inhibition at 0.1 mM
3-(4,6-diphenylpyridin-2-yl)phenol
-
12.9% inhibition at 0.1 mM
3-(4-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-phenoxy)propan-1-amine
3-(4-chlorophenyl)-1-(4'-hydroxyphenyl)-2-propen-1-one
-
chalcones (1,3-diaryl-2-propen-1-ones) are alpha, beta-unsaturated ketones with cytotoxic and anticancer properties. Compound has the highest Hammett and log P values (0.23 and 4.21, respectively) and exerted both highest cytotoxicity and strongest DNA topoisomerase I inhibition
3-(4-methylphenyl)-1-(4'-hydroxyphenyl)-2-propen-1-one
-
chalcones (1,3-diaryl-2-propen-1-ones) are alpha, beta-unsaturated ketones with cytotoxic and anticancer properties. Compound shows moderate interference with the DNA topoisomerase I
3-(4-phenyl-2,4'-bipyridin-6-yl)phenol
-
70.4% inhibition at 0.1 mM
3-(5-phenyl-1H-pyrrol-2-yl)-propanoic acid
-
0.05 mM, 35% vTopo RNase activity remaining
3-(6-phenyl-2,2'-bipyridin-4-yl)phenol
-
10.8% inhibition at 0.1 mM
3-(6-phenyl-2,3'-bipyridin-4-yl)phenol
-
8.8% inhibition at 0.1 mM
3-(6-phenyl-2,4'-bipyridin-4-yl)phenol
-
60.8% inhibition at 0.1 mM
3-(imidazolyl-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline hydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
3-(piperidin-1-yl)propyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
3-(pyrrolidin-1-yl)propyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
3-amino-4-chloro-9,10-dioxo-9,10-dihydroanthracene-2-sulfonic acid
-
-
3-amino-6-(3-aminopropyl)-5,6-dihydro-9-methoxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
-
-
3-amino-6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
3-amino-6-(3-azidopropyl)-5,6-dihydro-9-methoxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
-
3-benzo[1,3]dioxol-5-yl-1,1,1-trihydroxy-2-oxopropanoic acid
-
0.05 mM, 9% vTopo RNase activity remaining, 8% cTopo relaxation activity remaining
3-benzo[1,3]dioxol-5-yl-2-oxopropionic acid
-
potent inhibitor of the enzyme from vaccinia virus, does not inhibit the human enzyme
3-bromo-11-hydroxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
-
-
3-bromopropyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
3-cyano-5,11-dihydro-6-[3-(1H-imidazolyl)propyl]-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinoline
-
-
3-cyano-5,11-dihydro-6-[3-(dimethylamino)propyl]-5,11-dioxoindeno[1,2-c]isquinoline
-
-
3-cyano-6,11-dihydro-5,11-dioxo-6-(3-morpholinylpropyl)-5H-indeno[1,2-c]isoquinoline
-
-
3-cyano-6,11-dihydro-5,11-dioxo-6-[3-(dimethylamino)propyl]-5H-indeno[1,2-c]isoquinoline
-
-
3-iodo-9-methoxy-6-[3-(dimethylamino)propyl]-5H-indeno-[1,2-c]isoquinoline-5,11(6H)-dione
-
-
3-methoxy-5H-isoindolo[2,1-a]quinoxalin-6-one
-
-
3-morpholinopropyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
3-O-(benzenesulfonyloxy)-oleanolic acid
-
-
3-O-[N-(1-naphthyl)-carbamoyl]-17-beta-[N-(1-naphthyl)-carbamoyl]-oleanolic acid
-
-
3-O-[N-(1-naphthyl)-carbamoyl]-oleanolic acid
-
-
3-O-[N-(allyl)carbamoyl]-oleanolic acid
-
-
3-O-[N-(benzyl)carbamoyl]-17beta-O-[N-(benzyl)carbomyl]-oleanolic acid
-
-
3-O-[N-(benzyl)carbamoyl]-oleanolic acid
-
-
3-O-[N-(biphenyl)-p-carbamoyl]-oleanolic acid
-
-
3-O-[N-(phenylsulfonyl)-carbamoyl-17beta-N-(phenylsulfonyl)amide]-oleanolic acid
-
-
3-phenyl-1-(4'-hydroxyphenyl)-2-propen-1-one
-
chalcones (1,3-diaryl-2-propen-1-ones) are alpha, beta-unsaturated ketones with cytotoxic and anticancer properties. Compound shows moderate interference with the DNA topoisomerase I
3-pyridyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
The hypochromicity observed on DNA addition is too low for determination of binding constants
3-thiiranylmethyloxy-1-hydroxy-5-azaxanthone
-
50% and 27% inhibition at 0.1 mM and 0.02 mM, respectively
3-[(1-azabicyclo[2.2.2]oct-3-ylamino)methyl]-4,11-dihydroxy-1H-naphtho[2,3-f]indole-5,10-dione
-
-
3-[(1-hydroxyethyl-piperazine)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
similar activity as the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
3-[(1-methylpiperazinyl)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
weak activity
3-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoic acid hydrochloride
-
-
3-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]-isoquinolin-3-yl)amino]-3-oxopropanoic acid
-
-
3-[(dimethylamino)methyl]-4,11-dihydroxy-1H-naphtho[2,3-f]indole-5,10-dione
-
-
3-[(morpholinyl)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
3-[(thiomorpholinyl)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
similar activity as the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
3-[1-[(4-methylphenyl)sulfonyl]-2-phenyl-1H-indol-3-yl]prop-2-yn-1-yl 3-amino-2,3,6-trideoxy-b-D-arabino-hexopyranoside
-
80.1% inhibition at 0.1 mM
3-[2-(furan-2-yl)-6-phenylpyridin-4-yl]phenol
-
48.8% inhibition at 0.1 mM
3-[2-phenyl-6-(thiophen-2-yl)pyridin-4-yl]phenol
-
9.1% inhibition at 0.1 mM
3-[2-phenyl-6-(thiophen-3-yl)pyridin-4-yl]phenol
-
6.9% inhibition at 0.1 mM
3-[4-(1-ethyl-2-methyl-propenyl)-phenoxy]-benzoic acid
-
0.05 mM, 33% vTopo RNase activity remaining
3-[4-phenyl-6-(thiophen-2-yl)pyridin-2-yl]phenol
-
51.2% inhibition at 0.1 mM
3-[4-phenyl-6-(thiophen-3-yl)pyridin-2-yl]phenol
-
75.8% inhibition at 0.1 mM
3-[6-(furan-2-yl)-4-phenylpyridin-2-yl]phenol
-
10.2% inhibition at 0.1 mM
4,11-bis([2-[(2-hydroxyethyl)amino]ethyl]amino)-1H-naphtho[2,3-f]indole-5,10-dione
-
-
4,11-bis[(2-aminoethyl)amino]-1H-naphtho[2,3-f]indole-5,10-dione
-
-
4,11-bis[[2-(dimethylamino)ethyl]amino]-1H-naphtho[2,3-f]indole-5,10-dione
-
-
4,11-bis{[2-(methylamino)ethyl]amino}-1H-naphtho[2,3-f]indole-5,10-dione
-
-
4,11-dihydroxy-3-[(4-methylpiperazin-1-yl)methyl]-1H-naphtho[2,3-f]indole-5,10-dione
-
-
4,4',4'',4'''-ethane-1,1,2,2-tetrayltetrakis(2,6-dichlorophenol)
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 60%
4,4',4'',4'''-porphyrin-5,10,15,20-tetrayltetrabenzoic acid
-
-
4,4',4'',4'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis(4-methylmorpholin-4-ium) tetraiodide
-
-
4,4'-dimethyl-biphenyl-2,5,2',5'-tetraol
-
0.05 mM, 30% vTopo RNase activity remaining
4,4-bis(3,5-dibromo-4-hydroxyphenyl)pentanoic acid
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%
4-(1-methylaminomethylsulfanyl-ethyl)-benzene-1,2-diol
-
0.05 mM, 27% vTopo RNase activity remaining
4-(1H-benzimidazole-2-yl)phenol
-
Cpd III, 1H-benzimidazole derivative
4-(1H-benzo[d]imidazol-2-yl)phenol
4-(2-hydroxyethyl)-6-([2-[(2-hydroxyethyl)amino]ethyl]amino)-1,2,3,4-tetrahydronaphtho[2,3-f]quinoxaline-7,12-dione
-
-
4-(4,6-diphenylpyridin-2-yl)phenol
-
52.9% inhibition at 0.1 mM
4-(4-phenyl-2,3'-bipyridin-6-yl)phenol
-
44% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-2-(3-chlorophenyl)-6-(3-methylthiophen-2-yl) pyridine
-
5.9% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-2-(3-chlorophenyl)-6-(5-chlorothiophen-2-yl) pyridine
-
13% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-2-(4-chlorophenyl)-6-(3-methylthiophen-2-yl) pyridine
-
5.1% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-2-(5-chlorothiophen-2-yl)-6-(furan-2-yl) pyridine
-
23% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-2-(5-chlorothiophen-2-yl)-6-p-tolylpyridine
-
14% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-2-(furan-2-yl)-6-(3-methylthiophen-2-yl) pyridine
-
7.8% inhibition at 0.1 mM
4-(5-chlorofuran-2-yl)-6-(3-methylthiophen-2-yl)-2,3'-bipyridine
-
21% inhibition at 0.1 mM
4-(6-phenyl-2,4'-bipyridin-4-yl)phenol
-
57.5% inhibition at 0.1 mM
4-(furan-2-yl)-2-(pyridin-2-yl)-5H-chromeno[4,3-b]pyridine
-
4.4% inhibition at 0.1 mM
4-(furan-2-yl)-2-(thiophen-2-yl)-5H-chromeno [4,3-b]pyridine
-
9.2% inhibition at 0.1 mM
4-(furan-2-yl)-2-(thiophen-2-yl)-5H-chromeno[4,3-b]pyridine
-
-
4-(furan-2-yl)-2-phenyl-5H-chromeno[4,3-b]pyridine
-
-
4-(furan-3-yl)-2-(thiophen-2-yl)-5H-chromeno[4,3-b]pyridine
-
-
4-(furan-3-yl)-2-phenyl-5H-chromeno[4,3-b]pyridine
-
-
4-(furan-3-yl)-6-(thiophene-2-yl)-[2,4']-bipyridyl
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
4-(furan-3-yl)-6-(thiophene-3-yl)-[2,4']-bipyridyl
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
4-(pyridin-2-yl)-2-(thiophen-2-yl)-5H-chromeno[4,3-b]pyridine
-
-
4-(pyridin-2-yl)-2-(thiophen-3-yl)-5H-chromeno[4,3-b]pyridine
-
3.3% inhibition at 0.1 mM
4-(thiophene-3-yl)-6-(thiophene-2-yl)-[2,2']-bipyridyl
-
shows significant topoisomerase I inhibitory activities at 20 microM and 100 microM concentration
4-(thiophene-3-yl)-6-(thiophene-2-yl)-[2,4']-bipyridyl
-
shows significant topoisomerase I inhibitory activities at 20 microM and 100 microM concentration
4-chloro-N-[5-imino-1-(quinoxalin-2-yl)-2,5-dihydro-1H-1,2,4-triazol-3-yl]-5-methyl-2-sulfanylbenzenesulfonamide
-
-
4-hydroxy-5-methoxy-1-nitroanthracene-9,10-dione
-
-
4-methyl-5H-isoindolo[2,1-a]quinoxalin-6-one
-
-
4-phenyl-2-(pyridin-2-yl)-5H-chromeno[4,3-b]pyridine
-
3.1% inhibition at 0.1 mM
4-phenyl-2-(thiophen-2-yl)-5H-chromeno[4,3-b]pyridine
-
5.5% inhibition at 0.1 mM
4-[(2-carboxyphenyl)carbonyl]benzene-1,2-dicarboxylic acid
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%
4-[(3-(1-imidazolyl))propyloxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows strong DNA binding
4-[(3-(1-tetrazolyl))propoxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows weak DNA binding
4-[(3-(4-(2-hydroxyethyl)-1-piperazinyl))propyloxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows strong DNA binding
4-[(3-(4-methyl-1-piperazinyl))propyloxy]phenyl-1H-anthra-[1,2-d]imidazole-6,11-dione
-
shows strong DNA binding
4-[(3-(4-morpholinyl))propyloxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows weak DNA binding
4-[(3-diethylamino)propyloxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows strong DNA binding
4-[(3-dimethylamino)propyloxy]phenyl-1H-anthra[1,2-d]imidazole-6,11-dione
-
shows strong DNA binding
4-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoic acid
-
-
4-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoic acid hydrochloride
-
-
4-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-[(4-methylpiperazin-1-yl)methyl]phenol
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 100%
4-[2-(furan-2-yl)-6-phenylpyridin-4-yl]phenol
-
5.0% inhibition at 0.1 mM
4-[3-[ethyl(methyl)amino]propyl]furo[3,2-c]phenanthridine-5,10,11(4H)-trione
-
4-[4-phenyl-6-(thiophen-2-yl)pyridin-2-yl]phenol
-
4.9% inhibition at 0.1 mM
4-[4-phenyl-6-(thiophen-3-yl)pyridin-2-yl]phenol
-
20.4% inhibition at 0.1 mM
4-[5-(4-methyl-1-piperazinyl)-1H,1H'-2,5'-bibenzimidazol-2'-yl]phenol
-
Hoechst 33258
4-[6-(furan-2-yl)-4-phenylpyridin-2-yl]phenol
-
18.6% inhibition at 0.1 mM
4-[[(2-fluorophenyl)carbamoyl]amino]benzenesulfonamide
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 40%
4-[[(6-amino-3-methylpyrido[2,3-b]pyrazin-8-yl)amino]methyl]benzenesulfonamide
-
-
4-[[2-(6-amino-8-oxo-1,2,3,4,5,8-hexahydropyrido[2,3-b]pyrazin-2-yl)ethyl]amino]benzoic acid
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 100%
5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carbonitrile
-
-
5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylic acid
-
-
5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline-11-carbonitrile
-
-
5,12-dioxo-N-(2-(piperidin-1-yl)ethyl)-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
5,12-dioxo-N-(3-(piperidin-1-yl)propyl)-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
5,12-dioxo-N-(3-(pyrrolidin-1-yl)propyl)-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
5,12-dioxo-N-(3-phenylpropyl)-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
5,12-dioxo-N-phenethyl-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
5,5'-(1,1'-dihydroxy-8,8'-dimethoxy-6,6'-dimethyl-2,2'-binaphthalene-4,4'-diyl)bis(1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline-6,8-diol)
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 40%
5,6,7,8-Substituted-2-phenylthiochromen-4-ones
-
-
5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl D-allopyranoside
-
dideschlororebeccamycin, RM762, indolocarbazole derivative
5,9,11-trimethoxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
-
-
5-(2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyl-6-[(4-methylphenyl)sulfonyl]tetrahydrofuro[2,3-d][1,3]dioxole
-
shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 50%
5-(4-ethylpiperazin-1-yl)-11H-indeno[1,2-c]isoquinolin-11-ol
-
-
5-(4-ethylpiperazin-1-yl)-11H-indeno[1,2-c]isoquinolin-11-one
-
-
5-(4-ethylpiperazin-1-yl)-11H-indeno[1,2-c]isoquinoline
-
-
5-(4-methyl-1,4-diazepan-1-yl)-11H-indeno[1,2-c]isoquinolin-11-one
-
-
5-(4-methyl-1,4-diazepan-1-yl)-11H-indeno[1,2-c]isoquinoline
-
-
5-(4-methylpiperazin-1-yl)-11H-indeno[1,2-c]isoquinolin-11-ol
-
-
5-(4-methylpiperazin-1-yl)-11H-indeno[1,2-c]isoquinolin-11-one
-
-
5-(4-methylpiperazin-1-yl)-11H-indeno[1,2-c]isoquinoline
-
-
5-(4-methylpiperazin-1-yl)-2-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H-benzo[d]imidazole
5-(butylamino)-11H-indeno[1,2-c]isoquinolin-11-one
-
-
5-(morpholin-4-yl)-11H-indeno[1,2-c]isoquinolin-11-ol
-
-
5-(morpholin-4-yl)-11H-indeno[1,2-c]isoquinolin-11-one
-
-
5-(morpholin-4-yl)-11H-indeno[1,2-c]isoquinolin-11-yl acetate
-
-
5-(morpholin-4-yl)-11H-indeno[1,2-c]isoquinoline
-
-
5-(piperazin-1-yl)-11H-indeno[1,2-c]isoquinolin-11-one
-
-
5-amino-2-(4-amino-2-bromophenyl)benzoxazole
-
5-amino-2-(4-fluorophenyl)benzoxazole
-
5-amino-2-phenylbenzoxazole
-
5-chloro-4-(1H-benzimidazole-2-yl)phenol
-
Cpd I, 1H-benzimidazole derivative
5-deoxy-5-(5,11-dioxo-5,11-dihydro-6H-indeno[1,2-c]isoquinolin-6-yl)-D-arabinitol
-
-
5-methyl-4-(1H-benzimidazole-2-yl)phenol
-
Cpd II, 1H-benzimidazole derivative
5-nitro-2-phenoxymethyl-benzimidazole
-
5-phenyl-2'-(indolo-6-yl)bibenzimidazole
-
5P2'IBB
5-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoic acid
-
-
5-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoic acid hydrochloride
-
-
5-[[3-(dimethylamino)propyl]amino]-3-methylpyrimido[4,5-b]quinoline-2,4(3H,4aH)-dione
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 5 microM, using high-throughput screen, relaxation inhibition 70%
6'-(thiophene-2-yl)-[3,4',2',4'']-terpyridine
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
6'-(thiophene-2-yl)-[4,2',4',4'']-terpyridine
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
6-(1-hydroxypropan-2-yl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(2,3-dihydroxypropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(2-hydroxypropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-(1H-imidazol-1-yl)propyl)-8-methoxy-3-nitro-5Hindeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-amino-2-hydroxypropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-3-(methylamino)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-5,6-dihydro-8-methoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline hydrochloride
-
-
6-(3-aminopropyl)-5,6-dihydro-9-methoxy-3-iodo-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
-
6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
class of non-camptothecin topoisomerase I inhibitors, exert cytotoxicity by trapping the covalent complex formed between DNA and Top1during relaxation of DNA supercoils
6-(3-aminopropyl)-7-methoxy-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-aminopropyl)-9-methoxy-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-azidopropyl)-5,6-dihydro-8-methoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
-
6-(3-bromopropyl)-5,6-dihydro-8-methoxy-3-nitro-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
-
6-(3-homopiperazinyl-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-(3-hydroxy-2-oxopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-hydroxypropyl)-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-(3-piperazinyl-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
-
similar activity as the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-(3-thiazolylamino-1-propyl)-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
6-(4-methylpiperazin-1-yl)-2-(4-(2-(4-(oct-7-ynyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazole
6-(4-methylpiperazin-1-yl)-2-[4-[(prop-2-yn-1-yl)oxy]phenyl]-1H-benzimidazole
6-(4-methylpiperazine-1-carbonyl)indolizino[2,3-g]quinoline-5,12-dione
-
-
6-(furan-2-yl)-4-(furan-3-yl)-[2,2']-bipyridyl
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
6-(furan-2-yl)-4-(furan-3-yl)-[2,4']-bipyridyl
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
6-(furan-2-yl)-4-(thiophene-2-yl)-[2,4']-bipyridyl
-
shows significant topoisomerase I inhibitory activities at 20 microM and 100 microM concentration
6-(furan-2-yl)-4-(thiophene-3-yl)-[2,4']-bipyridyl
-
shows moderate topoisomerase I inhibitory activities when compared to camptothecin
6-(furan-2-yl)-[3,4',2',4'']-terpyridine
-
shows significant topoisomerase I inhibitory activities at 20 microM and 100 microM concentration
6-(morpholine-4-carbonyl)indolizino[2,3-g]quinoline-5,12-dione
-
-
6-(piperidine-1-carbonyl)indolizino[2,3-g]quinoline-5,12-dione
-
-
6-acetyl-7-amino-indolizino[2,3-g]quinoline-5,12-dione
-
-
6-acetyl-7-bromo-indolizino[2,3-g]quinoline-5,12-dione
-
-
6-acetyl-7-chloro-indolizino[2,3-g]quinoline-5,12-dione
-
-
6-acetyl-7-fluoro-indolizino[2,3-g]quinoline-5,12-dione
-
-
6-acetyl-7-hydroxy-indolizino[2,3-g]quinoline-5,12-dione
-
-
6-acetylindolizino[2,3-g]quinoline-5,12-dione
-
-
6-methylindolizino[2,3-g]quinoline-5,12-dione
-
-
6-N-(1-hydroxymethyl-2-hydroxy)ethylamino-12,13-dihydro-2,10-dihydroxy-13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,6(6H)-dione
-
also effective against cancer cells with P-glycoprotein-mediated resistance to adriamycin or taxol
6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-D-glucopyranosyl)-5G-indolo(2,3-a)pyrrolo(3,4-c)carbarole-5,7(6H)-dione
-
more potent than camptothecin for inhibiting the top1-mediated religation step
6-[(2-chlorobenzyl)sulfanyl]-9-(beta-L-ribofuranosyl)-9H-purin-2-amine
-
-
6-[(2R)-1-hydroxypropan-2-yl]-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-[(2R)-2,3-dihydroxypropyl]-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-[(2R)-2-hydroxypropyl]-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-[(2S)-1-hydroxypropan-2-yl]-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-[(2S)-2,3-dihydroxypropyl]-2,3-dimethoxy-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-[(2S)-2,3-dihydroxypropyl]-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-[(2S)-2-hydroxypropyl]-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
6-[(3-morpholylethylamino)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoic acid
-
-
6-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoic acid hydrochloride
-
-
6-[3-(1H-imidazol-1-yl)propyl]-2,3-dimethoxy-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[3-(1H-imidazol-1-yl)propyl]-2,3-dimethoxy-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
-
6-[3-(1H-imidazol-1-yl)propyl]-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione hydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[3-(1H-imidazol-1-yl)propyl]-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[3-(3-hydroxypiperidinyl)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline hydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[3-(4-aminopiperidinyl)-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline dihydrochloride
-
weak activity
6-[3-pyrazolyl-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline
-
similar activity as the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-[3-[(2-hydroxyethyl)amino]propyl]-2,3-dimethoxy-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
-
6-[3-[2-(1,2,4)]-triazolyl-1-propyl]-5,6-dihydro-2,3-dimethoxy-8,9-methylenedioxy-5,11-dioxo-11H-indeno[1,2-c]isoquinoline hydrochloride
-
higher activity than the parent compound 2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
6-{3-[(2-hydroxyethyl)amino]propyl}-2,3-dimethoxy-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
i.e. MJ-III-65
7,8-dimethoxy-2-pyridin-4-yl-4H-chromen-4-one
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 100%
7-(2-furoyl)-10-methoxyhomocamptothecin
-
-
7-(2-naphthoyl)-10-methoxyhomocamptothecin
-
-
7-(2-thenoyl)-10-methoxyhomocamptothecin
-
-
7-(3,5-dimethylbenzoyl)-10-methoxyhomocamptothecin
-
-
7-(4-chlorbenzoyl)-10-methoxyhomocamptothecin
-
-
7-(4-fluorobenzoyl)-10-methoxyhomocamptothecin
-
-
7-(4-methoxylbenzoyl)-10-methoxyhomocamptothecin
-
-
7-(4-toluyl)-10-methoxyhomocamptothecin
-
-
7-(4-triflouromethylbenzoyl)-10-methoxyhomocamptothecin
-
-
7-benzoyl-10-methoxyhomocamptothecin
-
-
7-butyryl-10-methoxyhomocamptothecin
-
-
7-cyclohexyl-10-methoxyhomocamptothecin
-
-
7-cyclohexylcabonyl-10-methoxyhomocamptothecin
-
-
7-cyclopentyl-10-methoxyhomocamptothecin
-
-
7-cyclopentylcabonyl-10-methoxyhomocamptothecin
-
-
7-cyclopropylcabonyl-10-methoxyhomocamptothecin
-
-
7-Ethyl-10-hydroxy-camptothecin
-
review of clinical pharmacokinetics
7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin
7-heptanoyl-10-methoxyhomocamptothecin
-
-
7-isobutyryl-10-methoxyhomocamptothecin
-
-
7-ketoroyleanone
-
diterpenoid from Orthosiphon wulfenioides
7-pentanoyl-10-methoxyhomocamptothecin
-
-
7-propionyl-10-methoxyhomocamptothecin
-
-
8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
8,9-dimethoxy-5-(2-N-methylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
8-bromo-9-cyano-7-(alpha-L-xylofuranosyl)-3,7-dihydroimidazo[1,2-c]pyrrolo[3,2-e]pyrimidin-4-ium
-
-
8-methoxy-6-(3-morpholinopropyl)-3-nitro-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
-
-
9,9'-[butane-1,4-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium) dichloride
-
synthetic protoberberine alkaloid, highly active
9,9'-[ethane-1,2-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium)dichloride
-
synthetic protoberberine alkaloid, highly active
9,9'-[heptane-1,7-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium) dichloride
-
synthetic protoberberine alkaloid, highly active
9,9'-[hexane-1,6-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium) dichloride
-
synthetic protoberberine alkaloid, highly active
9,9'-[pentane-1,5-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium) dichloride
-
synthetic protoberberine alkaloid, highly active
9,9'-[propane-1,3-diylbis(oxy)]bis(10-methoxy-5,6-dihydro[1,3]dioxolo[4,5-g]isoquino[3,2-a]isoquinolin-7-ium) dichloride
-
synthetic protoberberine alkaloid, highly active. Strongly stabilize the enzyme-DNA binary complex at low concentration (50100microM). From 0.1 to 1 mM, their ability to stabilize is weak
9-aminoacridine
-
acts as Top1 poison
9-O-(2-aminoethyl)berberine
-
synthetic protoberberine alkaloid
9-O-(2-hydroxyethyl)berberine
-
synthetic protoberberine alkaloid
9-O-[2-(1H-imidazol-1-yl)ethyl]berberine
-
synthetic protoberberine alkaloid
9-O-[2-(4-methylpiperazin-1-yl)ethyl]berberine
-
synthetic protoberberine alkaloid
antofine
-
alkaloid from Cynanchum komarovii
arciriaflavin A
-
RM62, indolocarbazole derivative
baicalein
-
(5,6,7-trihydroxyflavone), naturally occurring flavone, isolated from the stem-bark of Oroxylum indicum, binds to the free enzyme and also intercalates into the DNA at a very high concentration (300 mM) without binding to the minor grove
BAY 50-7950
-
IC50: 120 mg/ml
BAY 50-7952
-
IC50: 120 mg/l
berberrubine
-
natural protoberberine alkaloid
beta-octabromo-meso-tetra(4-carboxyl)phenyl porphyrin
-
-
beta-octaphenyl-meso-tetra(4-carboxyl)phenyl porphyrin
-
-
biphenyl-3,4'-diylbis(arsonic acid)
-
shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 0.1 microM, using high-throughput screen, relaxation inhibition 50%
bis(2,2-dichloro-6-[[2-(hydroxy-kO)benzylidene]amino-kN]-4H-1,3,2-benzodioxastannin-4-onato)copper(2+)
-
-
bis(2-hydroxy-5-[[2-(hydroxy-kO)benzylidene]amino-kN]benzoato)copper(2+)
-
-
bis(5,6-dimethyl-1H-benzo[d]imidazol-2-yl)methane
-
-
bis(5-methyl-1H-benzo[d]imidazol-2-yl)methane
-
-
bis-1,2-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-(ethylamino)-ethylamino]ethane tetra(trifluoroacetate)
-
bis-1,2-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-ethylamino]ethane bis(trifluoroacetate)
weak activity
bis-1,2-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propylamino]ethane bis(trifluoroacetate)
similar activity as 1 microM camptothecin
bis-1,3-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-ethylamino]propane bis(trifluoroacetate)
similar activity as 1 microM camptothecin
bis-1,3-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propylamino]propane bis(trifluoroacetate)
similar activity as 1 microM camptothecin
bis-1,3-[(5,6-dihydro-5,11-diketo-2,3-dimethoxy-11H-indeno-[1,2-c]isoquinoline)-6-ethylamino]propane bis(trifluoroacetate)
-
bis-1,3-[(5,6-dihydro-5,11-diketo-2,3-dimethoxy-11H-indeno-[1,2-c]isoquinoline)-6-propylamino]propane bis(trifluoroacetate)
-
bis-1,3-[(5,6-dihydro-5,11-diketo-3-nitro-11H-indeno[1,2-c]isoquinoline)-6-ethylamino]propane bis(trifluoroacetate)
-
bis-1,4-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-(6-propyl-tert-BOCamino)]butane
weak activity
bis-1,4-[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propylamino]butane bis(trifluoroacetate)
similar activity as 6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-(ethylamino)-ethyl]amine tris(trifluoroacetate)
similar activity as 6-(3-aminopropyl)-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-ethyl]amine
weak activity
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propyl]amine
weak activity
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)-6-propyl]methylamine
weak activity
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)]-(6-ethyl,6'-propyl)ammonium Trifluoroacetate
weak activity
bis[(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c]isoquinoline)]-(6-propyl,6'-butyl)amine hydrochloride
weak activity
bulgarein
-
stabilize inactive Top1cc
calothrixins
-
weak inhibitors of Top1
chrysin 6-C-beta-D-glucopyranosyl 8-C-alpha-L-arabinopyranoside
-
flavonoid from Scutellaria amoena
cis-2',5,7-trihydroxyflavanonol 3-O-beta-D-glucopyranoside
-
flavonoid from Scutellaria amoena
colcemid
-
microtubule inhibitor, arrests cells in M phase, followed by induction of apotosis, 1 and 5 ng/ml colcemid display only modest cytotoxic effects. 10, 50 and 100 ng/ml induce pronounced cell death as measured by flow cytometry analysis
coptisine
-
natural protoberberine alkaloid
corypalline
-
moderate inhibition
curcumin sulfate
i.e. diferuloylmethane sulfate
dehydrocavidine
-
moderate inhibition
dehydrocheilanthifoline
-
moderate inhibition
dehydrodiscretamine
-
moderate inhibition
diaqua(2,2'-diamino-4,4'-bi-1,3-thiazole)oxosulfato-vanadium(IV) tetrahydrate
-
-
-
dibiphenyl-4-yl(hydroxy)acetic acid
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%
dihydrobenzo[a]acridines
-
-
-
dihydroquercetin
i.e. (2R,3R)-2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2,3-dihydro-4H-1-benzopyran-4-one
dihydrotanshinone I
-
diterpenoid from Salvia castanea f. tomentos
dihydroxy[4-[(2-hydroxyethyl)sulfamoyl]phenyl]oxoantimonate(2-)
-
does not inhibit supercoil relaxation at 10 microM concentration. IC90 (compound concentration at which 90% or higher inhibition is observed) 5 microM, using high-throughput screen, relaxation inhibition 0%
enrofloxacin
-
inhibits DNA relaxation.When Vaccinia topoisomerase I is present with relaxed DNA in the presence of enrofloxacin, it executes the reverse reaction, supercoiling the DNA
erybraedin C
-
binds irreversibly to the enzyme alone, probably in proximity of the active site, without abolishing enzyme binding to the DNA
ethyl 10-amino-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 10-hydroxy-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 10-methyl-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 2-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]acetate hydrochloride
-
-
ethyl 2-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]acetate
-
-
ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]isoquinoline-6-carboxylate
-
-
ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxylate
-
-
ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]isoquinoline-11-carboxylate
-
-
ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
-
-
ethyl 6,11-dioxo-6,11-dihydrobenzo[f]-pyrido[1,2-alpha]indole 12-carboxylate
-
-
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
ethyl 7-bromo-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
ethyl 7-chloro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
ethyl 7-fluoro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
ethyl 7-hydroxy-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
ethyl 7-methyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
-
-
evodiamine
-
EVO, an alkaloidal compound isolated from Evodia rutaecarpa, is able to inhibit supercoiled plasmid DNA relaxation catalyzed by TopI by stabilizing topoisomerase I-DNA cleavable complex
feruloyl agmatine
-
moderate inhibition
fomitellic acid A
-
0.1 mM, 85% inhibition, IC50: 0.06 mM
fomitellic acid B
-
0.1 mM, 85% inhibition
gamma-aminobutyric acid
-
GABA, regulates the activity of topo I in mouse cerebellum sections, slightly and transiently inhibits topo I activity
gemcitabine
-
nucleoside analogue
glutamate
-
regulates the activity of topo I in mouse cerebellum sections. Exhibits a significant time-dependent inhibition of topo I activity but no effect of the enzyme protein level
glutathione S-transferase-Par-4
-
helichrysinA
-
flavonoid in Helichrysum pamphylicum
Heliquinomycin
-
at 0.1 mg/ml
hydroxylcamptothecin
topoisomerase I inhibitor
indeno[1,2-c]isoquinolinone
-
-
indolizino[2,3-g]quinoline-5,12-dione
-
-
indolizino[3,2-g]quinoline-5,12-dione
-
-
intoplicine
-
molecular interactions with DNA and topoisomerases and in ternary complexes, binding modes and biological effects of intoplicine derivatives
isodiospyrin
-
inhibits by direct binding to htopo I, inhibits relexation activity and kinase activity, antagonizes camptothecin-induced DNA cleavage by htopo I
isoquercitrin
-
flavonoid in Helichrysum pamphylicum
Jatrorrhizine
-
natural protoberberine alkaloid
jatrorubine
-
natural protoberberine alkaloid
lamellarin D
-
stabilize inactive Top1cc
luteolin 4'-O-beta-D-glucoside
-
flavonoid in Helichrysum pamphylicum
M13 DNA
-
strong inhibitor of relaxing activity
-
methyl (2R)-2-([3-[(3,3-dimethyloxiran-2-yl)methyl]-4-hydroxyphenyl]methyl)-4-hydroxy-3-(4-hydroxyphenyl)-5-oxo-2,5-dihydrofuran-2-carboxylate
i.e. butyrolactone I
methyl (2R)-4-hydroxy-2-[[4-hydroxy-3-(3-methylbutyl)phenyl]methyl]-3-(4-hydroxyphenyl)-5-oxo-2,5-dihydrofuran-2-carboxylate
i.e. butyrolactone III
methyl (7aS,12aS)-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carboxylate
methyl 2-(4-Hydroxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole-4-carboxylate
methyl 2-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-2-oxoacetate
-
-
methyl 2-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-2-oxoacetate
-
-
methyl 3-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoate
-
-
methyl 3-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoate
-
-
methyl 3-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-3-oxopropanoate
-
-
methyl 4-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoate
-
-
methyl 4-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoate
-
-
methyl 4-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-4-oxobutanoate
-
-
methyl 5-[(6-(3-((tert-butoxycarbonyl)amino)propyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoate
-
-
methyl 5-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoate
-
-
methyl 5-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-5-oxopentanoate
-
-
methyl 6-[(6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5Hindeno[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoate
-
-
methyl 6-[(6-methyl-5,11-dioxo-6,11-dihydro-5H-indeno-[1,2-c]isoquinolin-3-yl)amino]-6-oxohexanoate
-
-
methyl N-[(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetyl]glycinate
-
-
methyl [[5-carbamoyl-6-(methylsulfanyl)-4-oxo-3-phenyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl]sulfanyl]acetate
-
-
MJ-III-65
-
indenoisoquinoline analogue
monodentate [PtCl(diethylenetriamine)]Cl
-
presence of DNA adducts of bifunctional antitumor cisplatin or monodentate [PtCl(dien)]Cl in the substrate DNA inhibits eukaryotic top1 action, the adducts of cisplatin being more effective. Inhibition is markedly enhanced by camptothecin. Sequence preference of Pt-DNA adducts in the 161-bp substrate DNA fragment. Inhibition mechanism and interaction analysis, overview
morpholinodoxorubicin
-
traps topoisomerase I-DNA covalent complexes
Ms4585
-
inhibits the function of MsTopA in relaxing supercoiled DNA. The ribokinase, encoded by gene Ms4585, acts as a netaive regulator of TopA activity
-
N,N',N'',N'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis(2-hydroxy-N,N-dimethylethanaminium) tetrabromide
-
-
N,N',N'',N'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis(N,N-dimethylanilinium) tetrabromide
-
-
N,N',N'',N'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis(N-ethyl-N-methylethanaminium) tetrabromide
-
-
N,N',N'',N'''-[1,4-dihydroporphyrin-5,10,15,20-tetrayltetrakis(benzene-4,1-diylmethanediyl)]tetrakis[2-hydroxy-N-(2-hydroxyethyl)-N-methylethanaminium] tetrabromide
-
-
N,N,N-trimethyl-1H-pyridazino[4,3-b][1,4]benzothiazin-3-aminium
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 50%
N,N-diethyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N,N-diethyl-9-([2-(1H-indol-3-yl)ethyl]amino)acridine-3-carboxamide
-
-
N,N-dimethyl(6-methyl-10,11-dioxo-10,11-dihydrophenanthro[1,2-b]furan-1-yl)methanaminium (2E)-3-carboxyprop-2-enoate
-
-
N-(2-(1H-imidazol-1-yl)ethyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(2-(4-methylpiperazin-1-yl)ethyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(2-(dimethylamino)ethyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(2-(pyrrolidin-1-yl)ethyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(2-morpholinoethyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(3-(4-methylpiperazin-1-yl)propyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(3-(diethylamino)propyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(3-(dimethylamino)propyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-(3-morpholinopropyl)-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-butyl-11H-indeno[1,2-c]isoquinolin-5-amine
-
-
N-ethyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carboxamide
-
-
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
-
-
N-[1-[(4-ethylpiperazin-1-yl)carbonyl]-3-methylbutyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
-
-
N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide
-
-
N-[2-(Dimethylamino)ethyl]carboxamide derivatives of fused tetracyclic quinolines and quinoxalines
-
N-[6-(3-aminopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide
-
-
N-[6-(3-azidopropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide
-
-
N-[6-(3-hydroxypropyl)-5,11-dioxo-6,11-dihydro-5H-indeno[1,2-c]isoquinolin-3-yl]acetamide
-
-
N-[9-acetyl-6-(benzylsulfanyl)-9H-purin-2-yl]acetamide
-
-
naringenin
-
lowest degree of inhibition, flavonoid in Helichrysum pamphylicum
NH4Cl
-
can partially replace for NaCl in activation of enzyme forms MW 100000 and MW 110000
nick-containing oligonucleotides
-
inhibit DNA substrate relaxation. Synthesis of and enzyme inhibition by a series of oligonucleotides with various lengths that contain nick and topoisomerase I-binding sites, sequences, overview. The position of the nick as well as the length of the oligonucleotides are crucial factors for the inhibition of the nuclear enzyme
-
nick-containing oligonucleotides s
-
inhibit DNA substrate relaxation. Synthesis of and enzyme inhibition by a series of oligonucleotides with various lengths that contain nick and topoisomerase I-binding sites, sequences, overview. The position of the nick as well as the length of the oligonucleotides are crucial factors for the inhibition of the nuclear enzyme
-
oligo-1,3-thiazolecarboxamides
-
-
-
p-hydroxymercuribenzoate
-
-
palmatrubine
-
natural protoberberine alkaloid
phenazine-2,7-diylbis(arsonic acid)
-
IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 50%
platinum(II) complex
-
-
-
plukenetione A
-
can inhibit the unwinding activity of Top1
pyrazoloacridine
-
completely suppresses the ability of topoisomerase I to relax supercoiled DNA at a concentration of 0.008 mM, inhibits the enzyme without trapping cleavable complexes
pyridoxal 5'-diphospho-5'-adenosine
-
pyridoxal 5'-phosphate
competitive inhibitor of Candida guilliermondii topoisomerase I
R-3
-
a synthetic derivative of rebeccamycin that contains a methoxyglucose moiety appended to the indolocarbazole chromophore
R-4
-
the aglycone of a synthetic derivative of rebeccamycin that contains a methoxyglucose moiety appended to the indolocarbazole chromophore
Ro-61-6653
-
IC50: 120 mg/ml
Rv2436
inhibits the TopA activity on supercoiled DNA. The ribokinase, encoded by gene Rv2436, acts as a netaive regulator of TopA activity
-
S-Dimethylaminomethyl-N-(3,3,3-trichloro-1-hydroxy-prop-1-yl)-isothiourea
-
0.05 mM, 28% vTopo RNase activity remaining
Selenite
-
selenite induces topoisomerase I-DNA complexes in K562 cells
single-stranded M13 DNA
-
inhibits relation of negatively supercoiled DNA at 60-80°C
-
SN38
-
enzyme linker fluctuations can have an impact on SN38 binding by reducing the enzyme affinity for the drug. TOP1 mutations are involved in the development of SN38 resistance
SR proteins
-
inhibition of DNA nicking activity by SR proteins. Inhibition of the DNA nicking activity of Topo I by SRSF1 depends on RNA recognition motifs joined by a spacer, Topo I enzyme inhibition by spacer mutants, overview
-
tanshinone-1
less than 10% inhibition at 0.005 mM
Tax oncoprotein
-
from HTLV-1, inhibits DNA binding of topoisomerase I, which is the first step of the reaction catalyzed by the enzyme
-
tert-butyl 3-(4-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]-imidazol-2-yl)phenoxy)propylcarbamate
thiazole-containing oligopeptides
-
inhibitory effect increases with the number of thiazole units. Inhibitory properties of thiazole-containing oligopeptides containing 3 or 4 thiazole units are 3-10tímes better than those of distamycin A
-
Topostin B-553
-
interacts primarily with the enzyme and not with the substrate DNA
Topostin B-567
-
interacts primarily with the enzyme and not with the substrate DNA
topotecan hydrochloride
water soluble derivatives of camptothecin, hardly effective against bloodstream forms of Trypanosoma brucei
Tumor necrosis factor alpha
-
TNFalpha induces receptor-mediated apotosis. Receptor-mediated apoptosis induced by TNFalpha results in a very strong htopoI damage response, further indicating a general involvement of htopoI in apoptosis
-
tyrophostin AG-1387
-
the inhibitor alters the DNA relaxation process producing unique shapes of DNA molecules
Urea
inhibitory effect to W203A/W205A/W206A mutant
ursolic acid
-
complete inhibition above 0.2 mM, IC50: 0.25 mM
winchic acid
-
triterpenoid from Winchia calophylla
zinc bis(2-[(E)-[(2,2-dichloro-4-oxo-4H-1,3,2-benzodioxastannin-6-yl)imino]methyl]phenolate)
-
-
zinc bis(2-[(E)-[(3-carboxy-4-hydroxyphenyl)imino]methyl]phenolate)
-
-
Zn(isaepy)Cl2
complete inhibition at 0.3 mM
[2,2',2'',2''',2'''',2''''',2''''''-([24-((2-[diethyl(methyl)ammonio]ethyl)sulfanyl)-14,19-dihydro-29H,31H-tetrabenzoporphine-2,3,9,10,16,17,23-heptayl-k4N29,N30,N31,N32]heptasulfanediyl)heptakis(N,N,N-trimethylethanaminiumato)(2-)]zinc(8+) octaiodide
-
-
[3-[(E)-2-carboxyethenyl]phenyl](dihydroxy)oxoantimonate(2-)
[Cu(isaepy)H2O]ClO4
complete inhibition at 0.15 mM
[Cu(isapnsal)]ClO4
poor inhibition
[Zn(isapnsal)]ClO4
poor inhibition
(6aR,11aS)-11-[(4-methylphenyl)sulfonyl]-6,6a,11,11a-tetrahydro-5H-benzo[a]carbazole
-
binds selectively to PfTopoI
(6aR,11aS)-11-[(4-methylphenyl)sulfonyl]-6,6a,11,11a-tetrahydro-5H-benzo[a]carbazole
-
binds selectively to PfTopoI
(7aR,12aS)-5-methylidene-12-[(4-methylphenyl)sulfonyl]-7,7a,12,12a-tetrahydrobenzo[6,7]chromeno[4,3-b]indol-13(5H)-one
-
-
(7aR,12aS)-5-methylidene-12-[(4-methylphenyl)sulfonyl]-7,7a,12,12a-tetrahydrobenzo[6,7]chromeno[4,3-b]indol-13(5H)-one
-
-
(7aS,12aS)-10-methoxy-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
-
-
(7aS,12aS)-10-methoxy-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
-
-
(7aS,12aS)-11-methoxy-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carbaldehyde
-
-
(7aS,12aS)-11-methoxy-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carbaldehyde
-
-
(7aS,12aS)-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
-
-
(7aS,12aS)-5-methylidene-5,7,7a,12a-tetrahydro-13H-[1]benzofuro[3,2-c]benzo[g]chromen-13-one
-
-
(S)-camptothecin
-
-
10-Hydroxycamptothecin
-
-
10-Hydroxycamptothecin
-
camptothecin stabilizes Top1/dsDNA covalent complexes which ultimately results in cell death. Structure-activity-relationships for camptothecin and derivatives, modeling and calculation of interaction energies between bound camptothecin, and derivatives, and Top1/dsDNA, comparisons of different models, e.g. rotated +1 nucleoside and intercalated models, overview
10-Hydroxycamptothecin
-
preclinical pharmacology of the anticancer agent
2'-(4-(3,6,9,12,15,18-hexaoxahenicos-20-ynyloxy)phenyl)-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
2'-(4-(3,6,9,12,15,18-hexaoxahenicos-20-ynyloxy)phenyl)-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(but-3-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(but-3-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(hex-5-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2'-[4-[(hex-5-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
-
-
2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
novel functionalities appended to the lactam side chain of the indenoisoquinolines. Development of indenoisoquinoline Top1 inhibitors where the di(methoxy) and methylenedioxy substituents on the aromatic nucleus are combined with previously utilized and novel heterocyclic lactam side chains in an effort to improve the anticancer activity of the indenoisoquinolines
2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
i.e. NSC314622
2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
i.e. NSC 314622
2,3-dimethoxy-6-methyl-5H-[1,3]dioxolo[5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione
-
-
2-(4-((1-(2-azidoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
-
-
2-(4-((1-(2-azidoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
-
-
2-(4-(2-(4-(4-ethynylphenyl)-1H-1,2,3-triazol-1-yl)ethoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
-
-
2-(4-(2-(4-(4-ethynylphenyl)-1H-1,2,3-triazol-1-yl)ethoxy)-phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole
-
-
2-(4-ethoxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]-imidazole
-
-
2-(4-ethoxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]-imidazole
-
-
2-(4-hydroxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo-[d]imidazole-4-carboxylic acid
-
-
2-(4-hydroxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo-[d]imidazole-4-carboxylic acid
-
-
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
-
-
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
-
-
2-[4-(2-azidoethoxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
-
-
2-[4-(2-azidoethoxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
-
-
3-(4-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-phenoxy)propan-1-amine
-
-
3-(4-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)-phenoxy)propan-1-amine
-
-
4-(1H-benzo[d]imidazol-2-yl)phenol
-
-
4-(1H-benzo[d]imidazol-2-yl)phenol
-
-
5-(4-methylpiperazin-1-yl)-2-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H-benzo[d]imidazole
-
-
5-(4-methylpiperazin-1-yl)-2-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H-benzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2-(4-(2-(4-(oct-7-ynyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2-(4-(2-(4-(oct-7-ynyl)-1H-1,2,3-triazol-1-yl)ethoxy)phenyl)-1H-benzo[d]imidazole
-
-
6-(4-methylpiperazin-1-yl)-2-[4-[(prop-2-yn-1-yl)oxy]phenyl]-1H-benzimidazole
-
-
6-(4-methylpiperazin-1-yl)-2-[4-[(prop-2-yn-1-yl)oxy]phenyl]-1H-benzimidazole
-
-
7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin
-
-
7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin
-
strong synergism between irinotecan and 5-fluorouracil
7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin
-
i.e. irinotecan; review of clinical pharmacokinetics
8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
-
i.e. ARC-111
8,9-dimethoxy-5-(2-N,N-dimethylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
-
i.e. ARC-111
8,9-dimethoxy-5-(2-N-methylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
-
i.e. Genz-644282
8,9-dimethoxy-5-(2-N-methylaminoethyl)-2,3-methylenedioxy-5H-dibenzo[c,h][1,6]naphthyridin-6-one
-
i.e. Genz-644282
9-Hydroxyellipticine
-
-
Acriflavine
-
-
actinomycin D
-
-
actinomycin D
-
traps topoisomerase I-DNA covalent complexes
actinomycin D
-
10 mg/l, complete inhibition
Aminocatechol A-3253
-
Candida enzyme is more susceptible than the human enzyme
Aminocatechol A-3253
-
Candida enzyme is more susceptible than the human enzyme
ATP
-
physiological concentration
ATP
-
5 mM, 75% inhibition, ccomplete inhibition at 10 mM, regardless of Mg2+ concentration
Berberine
-
natural protoberberine alkaloid
Berberine
-
moderate inhibition
Berberine
-
a polyheterocyclic class I topoisomerase inhibitor with a structure resembling the intercalant drug benzo[a]acridine. Several berberine analogues tested
Berberine
is a polyheterocyclic class I topoisomerase inhibitor with a structure resembling the intercalant drug benzo[a]acridine. Several berberine analogues tested
Berberine
-
is a polyheterocyclic class I topoisomerase inhibitor with a structure resembling the intercalant drug benzo[a]acridine. Several berberine analogues tested
Berenil
-
-
Berenil
-
mitochondrial enzyme, not nuclear enzyme
camptothecin
-
camptothecin
-
in presence of the inhibitor, enzyme-supercoiled DNA complexes in which the enzyme is locked inside a relaxed region of the supercoiled DNA molecule are observed
camptothecin
-
DNA topoisomerase inhibitors are efficient and reversible inducers of premature senescence in normal cells
camptothecin
-
anticancer agent camptothecin (CPT)
camptothecin
-
class I topoisomerase poison. Pentacyclic natural alkaloid produced by the plant Camptotheca accuminata
camptothecin
-
Topoisomerase I inhibitor added for measuring the inhibition of DNA relaxation
camptothecin
-
topoisomerase I poison
camptothecin
-
Camptothecin poisoning of TopIB induces accumulation of positively supercoiled DNA in G1- and S-phase yeast cells. Mechanism of camptothecin-induced toxicity derives from TopIB-dependent accumulation of positive supercoils
camptothecin
-
when CPT is added the cleavage religation equilibrium is shifted toward cleavage
camptothecin
inhibitory effect to wild-type
camptothecin
-
79% inhibition at 0.1 mM
camptothecin
-
a selective inhibitor of DNA topoisomerase I. Camptothecin activates the transcription of low-abundance antisense RNAs at the HIF-1alpha gene locus in human cancer cells in a topoisomerase I-dependent manner, likely due to sustained drug interference with transcription regulation mechanisms leading to a more open chromatin conformation and de-repression/activation of antisense transcription. Top1cc is then a specific DNA damage induced by the drug, damage and repair mechanisms, detailed overview
camptothecin
-
the natural compound reversibly binds the covalent Top1-DNA complex slowing down the religation of the cleaved DNA strand, thus inducing cell death
camptothecin
-
camptothecin stabilizes Top1/dsDNA covalent complexes which ultimately results in cell death. Structure-activity-relationships for camptothecin and derivatives, modeling and calculation of interaction energies between bound camptothecin, and derivatives, and Top1/dsDNA, comparisons of different models, e.g. rotated +1 nucleoside and intercalated models, overview
camptothecin
-
response to camptothecin-based treatment is dependent on hTopI activity, and reduction in activity as well as mutations in hTopI result in camptothecin resistance
camptothecin
-
most widely studied inhibitor of type IB topoisomerase
camptothecin
-
class I topoisomerase poison. Pentacyclic natural alkaloid produced by the plant Camptotheca accuminata
camptothecin
-
Wild type and mutant sensitivity to camptothecin is determined in DNA cleavage assays. In vivo sensitivity to camptothecin also measured
camptothecin
-
Effect of CPT on the relaxation activity and equilibrium cleavage activity of fused topoisomerase I variants
camptothecin
-
well-known topo I poison
camptothecin
-
the best characterized topoisomerase IB inhibitor. Ability of the naturally occurring flavones to stabilize the covalent topoisomerase IDNA complex in vitro and in living cells is similar to that of the known topoisomerase I inhibitor camptothecin (CPT)
camptothecin
-
camptothecin sensitivity fold reduced compared with L/S
camptothecin
-
inhibitor of topoisomerase I
camptothecin
-
class I topoisomerase poison. Pentacyclic natural alkaloid producted by the plant Camptotheca accuminata. Camptothecin is cytotoxic for the erythrocytic forms of Plasmodium falciparum
camptothecin
-
inhibition of wild-type enzyme, no inhibition of mutant enzymes N726S and N726S
camptothecin
-
this drug inhibits the rejoining reaction of DNAtopoisomerase I thus creating, in the presence of a denaturing agent, single-strand breaks and behaving like a single-strand nuclease. In vivo induction of camptothecin-dependent DNA topoisomerase I cleavage sites. Cells are treated for cleavage-site induction. Three different aliquots are incubated with 50, 100 or 200 microM camptothecin for 2 min at room temperature (25°C)
camptothecin
-
anti cancer drug (CPT)
camptothecin
class I topoisomerase poison. Pentacyclic natural alkaloid produced by the plant Camptotheca accuminata
camptothecins
-
-
camptothecins
-
no inhibition
camptothecins
-
no inhibition
camptothecins
-
no inhibition
cisplatin
-
synergistic action between cisplatin and 7-ethyl-10-hydroxy-camptothecin in Kfr cells, a cisplatin resistant subline of the KF epithelial ovarian carcinoma cell line but not in the parent KF cells
cisplatin
-
presence of DNA adducts of bifunctional antitumor cisplatin or monodentate [PtCl(dien)]Cl in the substrate DNA inhibits eukaryotic top1 action, the adducts of cisplatin being more effective
Clorobiocin
-
-
coralyne
-
potent and selective Top1 inhibitor
coralyne
-
derivative of berberine has shown effectively combat Trypanosoma cruzi infection
coumermycin
-
weak
coumermycin
-
coumermycin A2
coumermycin
-
coumermycin A2
coumermycin
-
coumermycin A1
dihydrobetulinic acid
-
catalytic inhibitor of topoisomerase I, inhibits the suicidal cleavage reaction
dihydrobetulinic acid
-
DHBA inhibits by preventing enzyme DNA binary complex formation. Inhibits also topoisomerase II
dihydrobetulinic acid
-
DHBA, pentacyclic triterpenoid and catalytic inhibitor of both topoisomerases I and II that antagonizes camptothecin-induced cleavage, do not induce the formation of SDS-K+ precipitable complex, when Leishmania donovani cells incubated for 3 h with the compound
diospyrin
-
promotes protein conformational changes that can affect the kinase activity of Top1 altering SR protein phosphorylation and alternative splicing
diospyrin
-
naphthoquinone derivative
doxorubicin
-
-
doxorubicin
-
inhibits the enzyme without trapping cleavable complexes
EDTA
-
-
EDTA
complete inhibition of DNA relaxation at 10 mM
ellipticine
-
-
Ethidium bromide
-
-
Ethidium bromide
-
no inhibition
Ethidium bromide
-
mitochondrial enzyme, not nuclear enzyme
Ethidium bromide
-
0.25 mg/l, complete inhibition
Fe2+
-
competes with Zn2+. TopA is an iron and zinc binding protein. Whereas the zinc-bound TopA is fully active to relax the negatively supercoiled DNA, the iron-bound TopA has little or no enzyme activity. The C-terminal zinc-binding region, but not the N-terminal fragment, of TopA, is involved in the iron binding
Fe2+
-
the iron-bound enzyme fails to relax the negatively supercoiled DNA, the iron-bound YrdD has very little or no binding activity for single-stranded DNA. Iron-bound YrdD cannot protect ssDNA from the DNase I digestion
glutathione S-transferase-Par-4
-
-
-
glutathione S-transferase-Par-4
-
-
-
heparin
-
-
heparin
-
1 mg/ml, complete inhibition
Hoechst 33258
-
-
Hoechst 33258
-
5 mg/l, 70% inhibition
Hoechst 33342
-
-
Hydroxystilbamidine
-
-
indenoisoquinoline
-
indenoisoquinoline
NSC314622
irinotecan
-
-
irinotecan
-
a prodrug and it is activated by hydrolysis to the biologically active metabolite SN-38
irinotecan
-
water-soluble camptothecin derivative
irinotecan
-
i.e. CPT-11, a derivative of camptothecin and an anticancer agent in the treatment of metastatic colon cancer
irinotecan
-
topoisomerase I forms in vivo complexes with DNA substrates, the complexes are stabilized by irinotecan, which has DNA strand breaking ability, it leads to topisomerase poisoning and DNA damage, overview
irinotecan
water soluble derivatives of camptothecin, hardly effective against bloodstream forms of Trypanosoma brucei
isorauhimbinic acid
-
KCl
-
can partially replace for NaCl in activation of enzyme forms MW 100000 and MW 110000
Lampit
-
-
luteolin
-
naturally occurring flavone, binds to the free enzyme and also intercalates into the DNA at a very high concentration (300 mM) without binding to the minor grove
luteolin
-
highest degree of inhibition, flavonoid in Helichrysum pamphylicum
methyl (7aS,12aS)-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carboxylate
-
-
methyl (7aS,12aS)-5-methylidene-13-oxo-5,7a,12a,13-tetrahydro-7H-[1]benzofuro[3,2-c]benzo[g]chromene-9-carboxylate
-
-
methyl 2-(4-Hydroxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole-4-carboxylate
-
-
methyl 2-(4-Hydroxyphenyl)-6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazole-4-carboxylate
-
-
Mg2+
Effect of Mg2+ on bcTopo IIIbeta and ecTopo III-mediated DNA relaxation assays, high concentrations of Mg2+ (>2 mM) inhibit the relaxation
N-[2-(Dimethylamino)ethyl]carboxamide derivatives of fused tetracyclic quinolines and quinoxalines
-
-
-
N-[2-(Dimethylamino)ethyl]carboxamide derivatives of fused tetracyclic quinolines and quinoxalines
-
-
-
Na+
-
above 150 mM
Na+
-
enzyme forms MW 100000 and MW 110000: inhibition above 300 mM NaCl. Enzyme form MW 150000: inhibition above 50 mM NaCl
NaCl
-
above 100 mM
NaCl
inhibits DNA relaxation at over 60 mM
Nalidixic acid
-
no inhibition
Nalidixic acid
-
no inhibition
NEM
-
-
NEM
-
2 mM, complete inhibition
Neomycin sulfate
-
-
novobiocin
-
-
novobiocin
-
inhibits the ATPase activity
NSC 314622
-
cytotoxicity results of its direct action upon topoisomerase 1 in cells
NU/ICRF 505
-
-
palmatine
-
natural protoberberine alkaloid
palmatine
-
moderate inhibition
Par-4
-
tumor suppressor protein, prostate apoptosis response-4, binds to TOP1, via its leucine zipper domain, and prevents TOP1 interaction with the DNA
-
Par-4
-
tumor suppressor protein, prostate apoptosis response-4, binds to TOP1, via its leucine zipper domain, and prevents TOP1 interaction with the DNA
-
Par-4-GFP
-
-
-
poly(dG)
-
-
poly(dG)
-
not by other homopolymerical deoxyribonucleotides
quercetin
i.e. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-2,3-dihydro-4H-1-benzopyran-4-one
quercetin
-
naturally occurring flavone, binds to the free enzyme and also intercalates into the DNA at a very high concentration (300 mM) without binding to the minor grove
rebeccamycin
-
REB, indolocarbazole derivative
Rv1495
-
inhibits the DNA cleavage activity of MtbTopA as well as its function of relaxation of supercoiled DNA. An N-terminus fragment of Rv1495, designated Rv1495-N(29-56), lost mRNA cleavage activity, but retained a significant physical interaction and inhibitory effect on TopA proteins, overview. No DNA-binding activity is seen with Rv1495, even at a high protein concentration
-
Rv1495
-
inhibits the DNA cleavage activity of MsTopA as well as its function of relaxation of supercoiled DNA. An N-terminus fragment of Rv1495, designated Rv1495-N(29-56), lost mRNA cleavage activity, but retained a significant physical interaction and inhibitory effect on TopA proteins in vitro and in vivo. MsmTopA associates with Rv1495 in vivo because an obvious and a specific hybridization signal is detected. No DNA-binding activity is seen with Rv1495, even at a high protein concentration
-
single-stranded DNA
-
heat-denatured single-stranded DNA
single-stranded DNA
-
strong inhibitor of relaxation reaction
SN-38
-
active metabolite of CPT-11
spermidine
-
-
spermidine
-
4 mM, complete inhibition
tert-butyl 3-(4-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]-imidazol-2-yl)phenoxy)propylcarbamate
-
-
tert-butyl 3-(4-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]-imidazol-2-yl)phenoxy)propylcarbamate
-
-
topotecan
-
topotecan
-
Camptothecin analogue, induce cell death by poisoning DNA topoisomerase I, topotecan significantly hinders topoisomerase-mediated DNA uncoiling, with a more pronounced effect on the removal of positive (overwound) versus negative supercoils. Significant activity against adult and paediatric solid tumours
topotecan
-
water-soluble camptothecin derivative, topotecan mimics a DNA base-pair and binds at the site of DNA cleavage by intercalating between the upstream (?1) and downstream (+1) base-pairs interacting also with the enzyme, acting as an interfacial uncompetitive inhibitor
yohimbinic acid
-
[3-[(E)-2-carboxyethenyl]phenyl](dihydroxy)oxoantimonate(2-)
-
partial or complete inhibition of hTopo is only observed at relatively high compound concentrations in the range 5 to 20 microM
[3-[(E)-2-carboxyethenyl]phenyl](dihydroxy)oxoantimonate(2-)
-
shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 0.1 microM, using high-throughput screen, relaxation inhibition 70%
additional information
-
no substantial inhibitory activity with BAY 50-7952, Ro-61-6653 and BAY 50-7950
-
additional information
-
poly(ADP)ribosylation leads to a loss in relaxing activity
-
additional information
-
non-camptothecin DNA topoisomerase I inhibitors in cancer therapy
-
additional information
-
no substantial inhibitory activity with BAY 50-7952, Ro-61-6653 and BAY 50-7950
-
additional information
-
toxicity of drugs targeted against topoisomerase I is directly related to the ability of the drug to stimulate topo I-dependent DNA cleavage
-
additional information
-
10,21-dimercaptocamptothecin is not cytotoxic
-
additional information
-
rebeccamycin and other indolcarbazole derivatives induces significant levels radiosensitization and exhibit efficiency in inducing TOP1-mediated DNA damage
-
additional information
-
to get a rough estimate of the preferred distance between two htopoI molecules a deoxyoligonucleotide with a defined length covalently attached (190 nts, the so-called suicide substrate L193s). Labelling of DNA attached to htopoI with 32P to determine the size of the attached DNA fragment more precisely
-
additional information
-
-
additional information
-
series of natural and synthetic protoberberine alkaloid evaluated for their inhibitory activities towards DNA topoisomerase I. Natural, monomeric protoberberine alkaloids and their mono-modified congeners show only minor activities. Most of the dimeric protoberberine alkaloids are highly active
-
additional information
biological results for substituted compounds revealed a disagreement between the structure-activity relationships of monomeric indenoisoquinoline and bisindenoisoquinoline as Top1 inhibitors, but cytotoxicity maintained for both series of compounds. Bisindenoisoquinoline to determine effect of indenoisoquinoline dimerization on cytotoxicity and Top1 inhibition. It is conceivable that it could exert antitumor activity by targeting DNA itself, apart from Top1
-
additional information
-
biological results for substituted compounds revealed a disagreement between the structure-activity relationships of monomeric indenoisoquinoline and bisindenoisoquinoline as Top1 inhibitors, but cytotoxicity maintained for both series of compounds. Bisindenoisoquinoline to determine effect of indenoisoquinoline dimerization on cytotoxicity and Top1 inhibition. It is conceivable that it could exert antitumor activity by targeting DNA itself, apart from Top1
-
additional information
-
indenoisoquinoline topoisomerase I (Top1) inhibitors. lactam substituents possessing nitrogen heterocycles can provide highly cytotoxic compounds with potent Top1 inhibition. Molecular modeling of these compounds in complex with DNA and Top1 suggests that some of the lactam substituents are capable of interacting with the DNA base pairs above and below the site of intercalation and/or with Top1 amino acid residues, resulting in increased biological activity
-
additional information
-
biphenyl-3,4'-diylbis(arsonic acid) and 5-(2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyl-6-[(4-methylphenyl)sulfonyl]tetrahydrofuro[2,3-d][1,3]dioxole show no inhibition even at compound concentrations of 20 microM
-
additional information
-
tumor suppressor p53 not only plays a key role in the regulation of the htopoI response to UV-C irradiation but also to treatment with colcemid
-
additional information
-
3-(4-methoxyphenyl)-1-(4'-hydroxyphenyl)-2-propen-1-one and3-(2-thienyl)-1-(4'-hydroxyphenyl)-2-propen-1-one do not interfere with the enzyme
-
additional information
-
determination for every cell line: GI50 (concentration inhibiting 50% net cell growth), TGI (total growth inhibition), and LC50 (concentration leading to 50% net cell death)
-
additional information
-
partial inhibition of the Top1-DNAadduct formation upon addition of poly(ADP ribose) polymerase 1 in the absence of NAD+ is shown, whereas in the presence of NAD+ formation of a high molecular weight product, most likely corresponding to poly(ADP) ribosylated Top1-DNA adduct, is observed
-
additional information
molecular design, synthesis and docking study of benz[b]oxepines and 12-oxobenzo[c]phenanthridinones, inhibitory potencies against topo 1, overview. Cytotoxic activity of inhibitors against human cancer cell lines, overview
-
additional information
-
cytotoxicity and mechanism of action of a series of substituted 9-aminoacridines is evaluated using topoisomerase I and cancer cell growth inhibition assays, overview
-
additional information
-
inhibitory and cytotoxic potencies of inhibitor compounds, in vivo activity in cancer cell lines, overview. No or poor inhibition by compounds 1-ethyl-3-(benzimidazol-2-yl)-6-fluoro-7-(piperazin-1-yl)-4(1H)-quinolone, 1-ethyl-3-(benzimidazol-2-yl)-6-fluoro-7-(1-piperazin-1-yl)-1,8-naphthyridine-4(1H)-one, 6,8-bis(oxiran-2-ylmethoxy)benzo[b][1,8]naphthyridin-5(10H)-one, 6-hydroxy-8-(thiiran-2-ylmethoxy)benzo[b][1,8]naphthyridin-5(10H)-one, and 8-bis(thiiran-2-ylmethoxy)benzo[b][1,8]naphthyridin-5(10H)-one
-
additional information
-
inhibitory potencies and cytotoxicities versus human cancer cell lines of plant-originated triterpenoids and triterpenoid glycosides isolated from Aesculus pavia, diverse inactive compounds, overview
-
additional information
synthesis and inhibitory potency of a series of water-soluble aromathecins substituted at position 14 with diaminoalkanes of various lengths, that all show antiproliferative potency. Aromathecins with longer diaminoalkane substituents over 6Cs possess lower anti-top1 activity than their smaller counterparts with 2-4 Cs
-
additional information
-
design and synthesis of 60 2-thienyl-4-furyl-6-aryl pyridine derivatives, inhibitory potency and cytotoxicity analysis using human topoisomerase I and human cancer cell lines MCF-7, HeLa, DU145, and K562. The 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl) moiety has an important role in displaying biological activities. No or poor inhibition by 2-(2-chlorophenyl)-4-(furan-2-yl)-6-(3-methylthiophen-2-yl) pyridine, 2-(4-chlorophenyl)-4-(furan-2-yl)-6-(3-methylthiophen-2-yl) pyridine, 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-6-m-tolylpyridine, 2-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-6-p-tolylpyridine, 2-(2-chlorophenyl)-6-(5-chlorothiophen-2-yl)-4-(furan-3-yl) pyridine, 2-(3-chlorophenyl)-6-(5-chlorothiophen-2-yl)-4-(furan-3-yl) pyridine, 2-(4-chlorophenyl)-6-(5-chlorothiophen-2-yl)-4-(furan-3-yl) pyridine, 6-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-2, 2'-bipyridine, 6-(5-chlorothiophen-2-yl)-4-(furan-3-yl)-2,30-bipyridine, and 4-(5-chlorofuran-2-yl)-2-(4-chlorophenyl)-6-(5-chlorothiophen-2-yl) pyridine
-
additional information
-
inhibition mechanisms of cationic porphyrins and analogues, overview
-
additional information
-
inhibitor design and synthesis, anti-proliferative activity study in human cancer cell lines, effect of quinolone and naphthyridine derivatives on Top I activity, overview
-
additional information
cytotoxicities in cancer cells and topoisomerase I inhibitory activities of norindenoisoquinoline derivatives, molecular modeling, overview; inhibitor binding in the topoisomerase I-DNA covalent complex, molecular docking and quantum chemical calculations, overview
-
additional information
-
cytotoxicities in cancer cells and topoisomerase I inhibitory activities of norindenoisoquinoline derivatives, molecular modeling, overview; inhibitor binding in the topoisomerase I-DNA covalent complex, molecular docking and quantum chemical calculations, overview
-
additional information
-
evodiamine is slightly less cytotoxic than campothecin against breast MCF-7 carcinoma cells
-
additional information
-
a multiple metallation of the short nucleotide sequences on the scissile strand, immediately downstream of the cleavage site impedes the cleavage by top1
-
additional information
-
the benz[a]acridine analogues, noncharged bioisosteres of protoberberine alkaloids, are also Top1 inhibitors
-
additional information
-
inhibitory activity, cytotoxicity, and structure-activity relationship study of hydroxylated 2,4-diphenyl-6-aryl pyridines, overview. Hydroxyl substitution at 3- or 3'-position of phenyl ring on 2,4-diphenyl-6-aryl pyridines might be required in order to show significant topo inhibitory activity. No inhibition by 15, 35, and 31
-
additional information
-
various 5-amino group-substituted indeno[1,2-c]isoquinolines display potent topoisomerase I inhibitory activity as well as cytotoxicities against five different human tumor cell lines. Molecular modelling and docking using protein structure PDB ID 1SC7
-
additional information
-
topoisomerase I inhibition of glycosylated 2-phenyl-indoles, 2-phenyl-benzo[b]thiophenes and 2-phenyl-benzo[b]furans, overview. Analysis of cytotoxocity against three human non-tumor cell lines analyzed by the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) cell viability assay
-
additional information
-
topoisomerase I inhibitors act as anticancer drugs, overview. Bone marrow colony-forming unit, CFU, granulocyte macrophage CFU, and tumor cell CFU activity of topoisomerase I inhibitors, overview. CFU are bipotent hemopoietic stem cells. Human bone marrow colony-forming unit is more sensitive to the Top1 inhibitors than is mouse bone marrow colony-forming unit
-
additional information
-
molecular docking study, overview. No inhibition by 3-[3-[bis(2-hydroxyethyl)amino]-2-hydroxypropoxy]-1-hydroxy-9H-xanthen-9-one, 1-hydroxy-3-[2-hydroxy-3-[(3-hydroxypropyl)sulfanyl]propoxy]-9H-xanthen-9-one, 1-hydroxy-3-[2-hydroxy-3-[(2-hydroxyethyl)sulfanyl]propoxy]-9H-xanthen-9-one, 1-hydroxy-3-[2-hydroxy-3-(propylamino)propoxy]-9H-xanthen-9-one, 1-hydroxy-3-[2-hydroxy-3-(2-hydroxyethoxy)propoxy]-9H-xanthen-9-one, and 3-[3-[(2-chloroethyl)sulfanyl]-2-hydroxypropoxy]-1-hydroxy-9H-xanthen-9-one
-
additional information
-
synthesis of 2,4-diaryl chromenopyridines and evaluation of their topoisomerase II inhibitory activity, cytotoxicity, and structure-activity relationship, overview. 2-Furyl or 2-thienyl at 2- or 4-position of central pyridine is crucial in displaying topo I or II inhibitory activity and cytotoxicity. No inhibition by 18, 19,20, 21, 22, 23, 25, 29, 32, 33, and 35
-
additional information
-
Top1 can be inhibited by heterocyclic compounds such as indolocarbazoles and indenoisoquinolines. Carbohydrate and hydroxyl-containing side chains are essential for the biological activity of indolocarbazoles. Preparation and inhibitory potency of indenoisoquinolines substituted with short-chain alcohols, diols, and carbohydrates, cytotoxicity, Top1 poisoning activity of diol-substituted indenoisoquinolines is dependent upon stereochemistry, molecular modeling, docking studies, and structure-function relationships, overview. IC50 values for cytotoxic effects in human cancer cell lines, overview
-
additional information
-
binding constant values of heterobimetallic complexes including Sn2+ and Cu2+ or Zn2+, and ligand 5-{[(1E)-(2-hydroxyphenyl)methylene]amino}-2-hydroxybenzoic acid with the DNA, NMR and mass spectrometric structure analysis, inhibitory potencies, overview
-
additional information
-
no inhibition by etoposide. Design and semisynthetic reactions preparation of oleanane-type triterpene derivatives of Hibiscus sabdariffa plant-derived oleanolic acid based on docking studies, with topoisomerase I inhibitory activity, NMR spectroscopic structure analysis of the compounds, computer-assisted molecular modeling and docking, overview
-
additional information
-
7-acyl homocamptothecins as topoisomerase I inhibitors, inhibition of induced DNA cleavage and in vitro cytotoxicity against three cancer cell lines A-549, MDA-MB-435 and HCT-116, overview
-
additional information
-
design, synthesis, and evaluation of indenoisoquinolines that are dual inhibitors of both tyrosyl-DNA phosphodiesterase I and Top1, structure-activity relationships, ctotoxic activities, and molecular modeling, overview
-
additional information
-
inhibitor design and evaluation, DNA cleavage inhibition and cytotoxic activities, docking study, overview
-
additional information
-
isolation of six synthetic isoflavonoid derivatives that dock in the binding site of inhibitors camptothecin and topotecan inside the enzyme, no inhibition by LQB223, docking and molecular dynamics simulations, overview
-
additional information
-
the detection method termed rolling circle enhanced enzyme activity detection allows measurement of hTopI cleavage-religation activity at the single molecule level, and may be used to detect posttranslational enzymatic differences influencing camptothecin response
-
additional information
-
intercalation of indolocarbazole drugs in the DNA molecule is reinforced by the existance of the sugar moiety, which helps to stabilize the insertion complex by binding with the major groove of the ternary duplex DNA. The presence of chlorine atoms disminishes topoisomerase I inhibition
-
additional information
-
trapping of the covalent complex between LdTop1 and DNA by camptothecin resides in a pentapeptide placed upwards Arg-180, increases the sensitivity to the poison
-
additional information
-
Novel series of anthra[1,2-d]imidazole-6,11-dione derivatives, benzimidazole and anthraquinone derivatives are known topoisomerase inhibitors, synthesized nine imidazole-fused anthraquinone derivatives. The inhibition activity of the drugs is compared to that of the standard topo I poison cpt. Compounds with tetrazole, imidazole, or morpholine side chains exhibit potent inhibition activity against the parasitic enzyme, with activity significantly higher than that shown by camptothecin
-
additional information
-
Comparisons of topoisomerase I-mediated DNA cleavage induced by flavones and camptothecin. The rates of stabilization of cleavable complex by the flavones are 2-to 3fold reduced compared with that of camptothecin. Analysis of drug induced covalent topoisomerase IDNA complex formation in Leishmania donovani promastigotes by KCl-SDS precipitation assay. Treatment of the cells with baicalein, luteolin and quercetin for 5 h significantly increases the SDS-K+ precipitable complex compared with the untreated control cells. Relief of inhibition on dilution suggests that the selected flavones are acting reversibly against topoisomerase I. Fluorescence spectroscopy used to check directly the binding of luteolin, baicalein and quercetin to the enzyme (LdTOP1LS). Fluorescence titration data reveal that these selected flavones interact with free enzyme and perhaps explain for stronger inhibition in the enzymedrug pre-incubation experiments. Ability of the selected flavones to displace ethidium bromide from DNA is determined by a fluorescence emission assay. Effect of flavones on single turnover cleavage and religation activity measured, interaction of these flavones with enzyme during trans-esterification reaction with DNA is a pre-requirement for the stabilization of topoisomerase I-cleavable complex and subsequently inhibiting the religation step
-
additional information
-
elsamicin A might not be a topoisomerase I inhibitor, but behaves as an intercalating agent in DNA unwinding
-
additional information
-
PARP inhibitors prevent the glutamate, but not GABA, induced decrease in topo I activity
-
additional information
-
topoisomerase I inhibitors act as anticancer drugs, overview. Bone marrow colony-forming unit, CFU, granulocyte macrophage CFU, and tumor cell CFU activity of topoisomerase I inhibitors, overview. CFU are bipotent hemopoietic stem cells. Human bone marrow colony-forming unit is more sensitive to the Top1 inhibitors than is mouse bone marrow colony-forming unit
-
additional information
oligonucleotides containing the specific recognition sequence inhibit the activity of the enzyme, as well as the monoclonal antibody 2F3G4, developed against MstopoI inhibited the relaxation activity of the enzyme. No inhibition with non-specific oligonucleotides
-
additional information
-
oligonucleotides containing the specific recognition sequence inhibit the activity of the enzyme, as well as the monoclonal antibody 2F3G4, developed against MstopoI inhibited the relaxation activity of the enzyme. No inhibition with non-specific oligonucleotides
-
additional information
-
isolation of six synthetic isoflavonoid derivatives that dock in the binding site of inhibitors camptothecin and topotecan inside the enzyme, cytotoxicity in CQ-sensitive (3D7) or CQ-resistant (W2) parasites, overview
-
additional information
-
no inhibition: oxolinic acid
-
additional information
-
study of the action of DNA topoisomerase-targeted drugs
-
additional information
no inhibition by nalidixic acid and etoposide, and by spermidine
-
additional information
-
no inhibition by nalidixic acid and etoposide, and by spermidine
-
additional information
-
extracts from Greek domestic grapes are effective in inhibiting wheat germ topoisomerase I activity
-
additional information
-
using molecular beacon assay for topo I to blindly screen a 1990-member small-molecule library and to identify several specific inhibitors of the poxvirus topoisomerase
-
additional information
-
Poxviridae topoisomerase IB is insensitive to camptothecin. Because Poxviridae topoisomerase IB is not essential for the viral life cycle, the preferred strategy would be to develop agents that act as topoisomerase poisons rather than catalytic inhibitors. By trapping the cleavage complex, drug treatment could either fragment the viral genome or block early transcription by placing a covalently attached protein in the path of RNA polymerase. High-throughput screen identified nineteen compounds with activity against vaccinia topoisomerase IB with IC50 values in the low micromolar range and displayed no inhibition of human topoisomerase IB
-
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0.00323
(S)-camptothecin
Homo sapiens
-
-
0.01029 - 0.0158
11-acetyl-10-amino-indolizino[3,2-g]quinoline-5,12-dione
0.0002 - 0.0124
11-acetyl-10-bromo-indolizino[3,2-g]quinoline-5,12-dione
0.0015 - 0.022
11-acetyl-10-chloro-indolizino[3,2-g]quinoline-5,12-dione
0.00139 - 0.0127
11-acetyl-10-fluoro-indolizino[3,2-g]quinoline-5,12-dione
0.0163
11-acetyl-10-hydroxy-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0014 - 0.01471
11-acetylindolizino[3,2-g]quinoline-5,12-dione
0.0055
11-hydroxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
Homo sapiens
-
-
0.0091
11-hydroxy-2-methyl-8-nitro-4H-naphtho[2,3-h]chromene-4,7,12-trione
Homo sapiens
-
-
0.00706
11-hydroxy-2-phenyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
Homo sapiens
-
-
0.0215
11-methylindolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.00715
11-[2-(dimethylamino)ethoxy]-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
Homo sapiens
-
-
0.05
2'-(4-(3,6,9,12,15,18-hexaoxahenicos-20-ynyloxy)phenyl)-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzo[d]imidazole
Escherichia coli
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.00663 - 0.05
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
0.0055 - 0.2541
2'-[4-[(but-3-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
0.00247 - 0.05
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
0.00457 - 0.05
2'-[4-[(hex-5-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
0.4435
2-(4-chlorobenzyl)benzoxazole
Bos taurus
-
0.0215 - 0.05
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
0.00266 - 0.00511
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[2-methyl-1-(morpholin-4-ylcarbonyl)propyl]acetamide
0.00126 - 0.00223
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
0.0141
2-phenoxymethylbenzimidazole
Bos taurus
-
0.00495
3,10-dibromo-11-hydroxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
Homo sapiens
-
-
0.0012
3,3'-diindolylmethane
Leishmania donovani
-
potent inhibitor of Leishmania donovani topoisomerase I
0.0065
3-bromo-11-hydroxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione
Homo sapiens
-
-
0.0015
4,11-bis[(2-aminoethyl)amino]-1H-naphtho[2,3-f]indole-5,10-dione
Homo sapiens
-
IC50 values 0.0005 mM to 0.0015 mM for 4,11-bis([2-[(2-hydroxyethyl)amino]ethyl]amino)-1H-naphtho[2,3-f]indole-5,10-dione, 0.0015 mM to 0.0035 mM for 4,11-bis[[2-(methylamino)ethyl]amino]-1H-naphtho[2,3-f]indole-5,10-dione, above 0.0035 mM for 4,11-bis[[2-(dimethylamino)ethyl]amino]-1H-naphtho[2,3-f]indole-5,10-dione
0.01175
4,4',4'',4'''-porphyrin-5,10,15,20-tetrayltetrabenzoic acid
Homo sapiens
-
-
0.16
4-hydroxy-5-methoxy-1-nitroanthracene-9,10-dione
Homo sapiens
-
-
0.1341
5-amino-2-(4-amino-2-bromophenyl)benzoxazole
Bos taurus
-
0.1323
5-amino-2-(4-fluorophenyl)benzoxazole
Bos taurus
-
0.495
5-amino-2-phenylbenzoxazole
Bos taurus
-
0.248
5-nitro-2-phenoxymethyl-benzimidazole
Bos taurus
-
0.01224 - 0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
0.004 - 0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
0.0032 - 0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
0.0028 - 0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
0.0122 - 0.0223
6-acetyl-7-amino-indolizino[2,3-g]quinoline-5,12-dione
0.00021 - 0.0117
6-acetyl-7-bromo-indolizino[2,3-g]quinoline-5,12-dione
0.00019 - 0.00783
6-acetyl-7-chloro-indolizino[2,3-g]quinoline-5,12-dione
0.00017 - 0.00526
6-acetyl-7-fluoro-indolizino[2,3-g]quinoline-5,12-dione
0.0176 - 0.02485
6-acetyl-7-hydroxy-indolizino[2,3-g]quinoline-5,12-dione
0.00086 - 0.00792
6-acetylindolizino[2,3-g]quinoline-5,12-dione
0.0122 - 0.0142
6-methylindolizino[2,3-g]quinoline-5,12-dione
0.109
aesculioside IIa
Homo sapiens
-
-
0.118
aesculioside IIb
Homo sapiens
-
-
0.111
aesculioside IIc
Homo sapiens
-
-
0.024
aesculioside IId
Homo sapiens
-
-
0.119
aesculioside IIIa
Homo sapiens
-
-
0.16
aesculioside IIIb
Homo sapiens
-
-
0.132
aesculioside IIIc
Homo sapiens
-
-
0.049
aesculioside IIId
Homo sapiens
-
-
0.045
aesculioside IIIe
Homo sapiens
-
-
0.054
aesculioside IIIf
Homo sapiens
-
-
0.053
aesculioside IV-23C1
Homo sapiens
-
-
0.027
aesculioside IV-23D1
Homo sapiens
-
-
0.033
aesculioside IV-23E
Homo sapiens
-
-
0.052
aesculioside IVa
Homo sapiens
-
-
0.036
aesculioside IVb
Homo sapiens
-
-
0.05
aesculioside IVc
Homo sapiens
-
-
0.00234
beta-octabromo-meso-tetra(4-carboxyl)phenyl porphyrin
Homo sapiens
-
-
0.0034
beta-octaphenyl-meso-tetra(4-carboxyl)phenyl porphyrin
Homo sapiens
-
-
0.025 - 0.526
camptothecin
0.00009 - 0.0002
epirubicin
0.019 - 0.0235
ethyl 10-amino-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.0011 - 0.0208
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.0022 - 0.0199
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.0012 - 0.0062
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.0233 - 0.0238
ethyl 10-hydroxy-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.00927 - 0.01165
ethyl 10-methyl-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.00088 - 0.00096
ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
0.0019 - 0.01445
ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
0.01643 - 0.02341
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
0.002 - 0.0103
ethyl 7-bromo-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
0.0021 - 0.00737
ethyl 7-chloro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
0.00137 - 0.00701
ethyl 7-fluoro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
0.0072
ethyl 7-hydroxy-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for GLC-82 cells
0.00022 - 0.0145
ethyl 7-methyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
0.0018 - 0.0099
etoposide
0.00602
evodiamine
Homo sapiens
-
-
0.06
fomitellic acid A
Homo sapiens
-
0.1 mM, 85% inhibition, IC50: 0.06 mM
0.0195 - 0.02286
Hoechst 33258
0.005 - 0.02983
Hoechst 33342
0.0115 - 0.01697
indolizino[2,3-g]quinoline-5,12-dione
0.0123 - 0.0202
indolizino[3,2-g]quinoline-5,12-dione
0.00668 - 0.00744
JDC-108
0.00213 - 0.00288
methyl N-[(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetyl]glycinate
0.00109 - 0.00288
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
0.00244 - 0.00794
N-[1-[(4-ethylpiperazin-1-yl)carbonyl]-3-methylbutyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
0.0000063
nick-containing oligonucleotide, nick-containing oligonucleotides
Homo sapiens
-
-
-
0.00002 - 0.047
NSC 725776
0.00006 - 0.047
NSC 743400
0.02149
tanshinone-1
Homo sapiens
at pH 8.0 and 37°C
0.0295
topopyrone C
Homo sapiens
-
-
0.00118
topotecan
Homo sapiens
-
-
0.25
ursolic acid
Homo sapiens
-
complete inhibition above 0.2 mM, IC50: 0.25 mM
additional information
additional information
-
0.01029
11-acetyl-10-amino-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.0103
11-acetyl-10-amino-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0158
11-acetyl-10-amino-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.0002
11-acetyl-10-bromo-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.00156
11-acetyl-10-bromo-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00468
11-acetyl-10-bromo-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0124
11-acetyl-10-bromo-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.0015
11-acetyl-10-chloro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.0161
11-acetyl-10-chloro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0161
11-acetyl-10-chloro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.022
11-acetyl-10-chloro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00139
11-acetyl-10-fluoro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00675
11-acetyl-10-fluoro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.00928
11-acetyl-10-fluoro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.0127
11-acetyl-10-fluoro-indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0014
11-acetylindolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.0019
11-acetylindolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0127
11-acetylindolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.01471
11-acetylindolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00663
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
2'-[4-([6-[(but-3-yn-1-yl)oxy]hexyl]oxy)phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.0055
2'-[4-[(but-3-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.2541
2'-[4-[(but-3-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Homo sapiens
-
pH and temperature not specified in the publication
0.00247
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
2'-[4-[(heptadec-16-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.00457
2'-[4-[(hex-5-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
2'-[4-[(hex-5-yn-1-yl)oxy]phenyl]-6-(4-methylpiperazin-1-yl)-1H,3'H-2,5'-bibenzimidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.0215
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
2-(4-[[1-(6-azidohexyl)-1H-1,2,3-triazol-4-yl]methoxy]phenyl)-6-(4-methylpiperazin-1-yl)-1H-benzimidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.00266
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[2-methyl-1-(morpholin-4-ylcarbonyl)propyl]acetamide
Homo sapiens
-
for HT-29 cells
0.00511
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[2-methyl-1-(morpholin-4-ylcarbonyl)propyl]acetamide
Homo sapiens
-
for A549 cells
0.00126
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
Homo sapiens
-
for HT-29 cells
0.00184
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
Homo sapiens
-
for A549 cells
0.00194
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
Homo sapiens
-
for MCF-7 cells
0.00223
2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-N-[3-methyl-1-[(4-methylpiperazin-1-yl)carbonyl]butyl]acetamide
Homo sapiens
-
for Bel-7402 cells
0.01224
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(10-(prop-2-ynyloxy)-decyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.004
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(12-(prop-2-ynyloxy)-dodecyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.0032
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(6-(prop-2-ynyloxy)-hexyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.0028
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Escherichia coli
-
pH and temperature not specified in the publication
0.05
6-(4-methylpiperazin-1-yl)-2'-(4-(8-(prop-2-ynyloxy)-octyloxy)phenyl)-1H,3'H-2,5'-bibenzo[d]imidazole
Homo sapiens
-
IC50 above 0.05 mM, pH and temperature not specified in the publication
0.0122
6-acetyl-7-amino-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0223
6-acetyl-7-amino-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00021
6-acetyl-7-bromo-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00201
6-acetyl-7-bromo-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.00215
6-acetyl-7-bromo-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.0117
6-acetyl-7-bromo-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.00019
6-acetyl-7-chloro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00023
6-acetyl-7-chloro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.00685
6-acetyl-7-chloro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.00783
6-acetyl-7-chloro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.00017
6-acetyl-7-fluoro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00231
6-acetyl-7-fluoro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.00526
6-acetyl-7-fluoro-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0176
6-acetyl-7-hydroxy-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.0195
6-acetyl-7-hydroxy-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.02485
6-acetyl-7-hydroxy-indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.00086
6-acetylindolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.00792
6-acetylindolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.0122
6-methylindolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.01246
6-methylindolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.0142
6-methylindolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0015
baicalein
Leishmania donovani
-
LdTOP1LS pre-incubated separately with different concentrations for 5 min at 37°C in relaxation buffer followed by addition of pBluescript(SK+) DNA and further incubated for 15 min at 37°C
0.009
baicalein
Leishmania donovani
-
Quantitative representation of enzyme inhibition in the presence of flavones in relaxation experiments
0.025
camptothecin
Homo sapiens
-
at pH 7.5 and 25°C
0.526
camptothecin
Bos taurus
-
0.00009
epirubicin
Homo sapiens
-
wild type enzyme from HCT-116 cells, pH and temperature not specified in the publication
0.00011
epirubicin
Homo sapiens
-
wild type enzyme from LoVo cells, pH and temperature not specified in the publication
0.00018
epirubicin
Homo sapiens
-
wild type enzyme from HT-29 cells, pH and temperature not specified in the publication
0.0002
epirubicin
Homo sapiens
-
mutant enzyme R364K/G717R from HCT-116 cells, pH and temperature not specified in the publication
0.019
ethyl 10-amino-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.0235
ethyl 10-amino-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.0011
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.0024
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.01147
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for HL-60 cells
0.0208
ethyl 10-bromo-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0022
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.00973
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.01542
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for HL-60 cells
0.0199
ethyl 10-chloro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0012
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.0017
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.00551
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for HL-60 cells
0.0062
ethyl 10-fluoro-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0233
ethyl 10-hydroxy-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.0238
ethyl 10-hydroxy-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.00927
ethyl 10-methyl-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.01165
ethyl 10-methyl-5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for HL-60 cells
0.00088
ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.00096
ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0019
ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.0024
ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for GLC-82 cells
0.00638
ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for MCF-7 cells
0.01445
ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline 11-carboxylate
Homo sapiens
-
for HL-60 cells
0.01643
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.01758
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.0209
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.02341
ethyl 7-amino-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for GLC-82 cells
0.002
ethyl 7-bromo-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.00932
ethyl 7-bromo-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.0103
ethyl 7-bromo-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0021
ethyl 7-chloro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for NCI-H460 cells
0.00652
ethyl 7-chloro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.00737
ethyl 7-chloro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.00137
ethyl 7-fluoro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.00701
ethyl 7-fluoro-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.00022
ethyl 7-methyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for HL-60 cells
0.00183
ethyl 7-methyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for GLC-82 cells
0.0145
ethyl 7-methyl-5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline 6-carboxylate
Homo sapiens
-
for MCF-7 cells
0.0018
etoposide
Homo sapiens
-
wild type enzyme from LoVo cells, pH and temperature not specified in the publication
0.0044
etoposide
Homo sapiens
-
mutant enzyme R364K/G717R from HCT-116 cells, pH and temperature not specified in the publication
0.0063
etoposide
Homo sapiens
-
wild type enzyme from HCT-116 cells, pH and temperature not specified in the publication
0.0099
etoposide
Homo sapiens
-
wild type enzyme from HT-29 cells, pH and temperature not specified in the publication
0.0195
Hoechst 33258
Escherichia coli
-
at pH 7.9 and 37°C
0.02286
Hoechst 33258
Homo sapiens
-
at pH 7.9 and 37°C
0.005
Hoechst 33342
Homo sapiens
-
IC50 above 0.05 mM, at pH 7.9 and 37°C
0.02983
Hoechst 33342
Escherichia coli
-
at pH 7.9 and 37°C
0.0115
indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0156
indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.01697
indolizino[2,3-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.0123
indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for NCI-H460 cells
0.01468
indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for HL-60 cells
0.0167
indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for GLC-82 cells
0.0202
indolizino[3,2-g]quinoline-5,12-dione
Homo sapiens
-
for MCF-7 cells
0.00668
JDC-108
Homo sapiens
-
for Bel-7402 cells
0.00744
JDC-108
Homo sapiens
-
for HT-29 cells
0.0025
luteolin
Leishmania donovani
-
LdTOP1LS pre-incubated separately with different concentrations for 5 min at 37°C in relaxation buffer followed by addition of pBluescript(SK+) DNA and further incubated for 15 min at 37°C
0.014
luteolin
Leishmania donovani
-
Quantitative representation of enzyme inhibition in the presence of flavones in relaxation experiments
0.00213
methyl N-[(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetyl]glycinate
Homo sapiens
-
for A549 cells
0.00223
methyl N-[(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetyl]glycinate
Homo sapiens
-
for MCF-7 cells
0.00288
methyl N-[(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetyl]glycinate
Homo sapiens
-
for HT-29 cells
0.00109
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for HCT-8 cells
0.00186
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for A549 cells
0.00191
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for Bel-7402 cells
0.00191
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for MCF-7 cells
0.00288
N-[1-benzyl-2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for HT-29 cells
0.00244
N-[1-[(4-ethylpiperazin-1-yl)carbonyl]-3-methylbutyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for MCF-7 cells
0.00348
N-[1-[(4-ethylpiperazin-1-yl)carbonyl]-3-methylbutyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for HT-29 cells
0.00794
N-[1-[(4-ethylpiperazin-1-yl)carbonyl]-3-methylbutyl]-2-(6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)acetamide
Homo sapiens
-
for A549 cells
0.00002
NSC 725776
Homo sapiens
-
wild type enzyme from LoVo cells, pH and temperature not specified in the publication
0.00003
NSC 725776
Homo sapiens
-
wild type enzyme from HT-29 cells, pH and temperature not specified in the publication
0.00006
NSC 725776
Homo sapiens
-
wild type enzyme from HCT-116 cells, pH and temperature not specified in the publication
0.047
NSC 725776
Homo sapiens
-
mutant enzyme R364K/G717R from HCT-116 cells, pH and temperature not specified in the publication
0.00006
NSC 743400
Homo sapiens
-
wild type enzyme from LoVo cells, pH and temperature not specified in the publication
0.00007
NSC 743400
Homo sapiens
-
wild type enzyme from HT-29 cells, pH and temperature not specified in the publication
0.00017
NSC 743400
Homo sapiens
-
wild type enzyme from HCT-116 cells, pH and temperature not specified in the publication
0.047
NSC 743400
Homo sapiens
-
mutant enzyme R364K/G717R from HCT-116 cells, pH and temperature not specified in the publication
0.0055
quercetin
Leishmania donovani
-
LdTOP1LS pre-incubated separately with different concentrations for 5 min at 37°C in relaxation buffer followed by addition of pBluescript(SK+) DNA and further incubated for 15 min at 37°C
0.017
quercetin
Leishmania donovani
-
Quantitative representation of enzyme inhibition in the presence of flavones in relaxation experiments
0.00002
SN-38
Homo sapiens
-
wild type enzyme from LoVo cells, pH and temperature not specified in the publication
0.00005
SN-38
Homo sapiens
-
wild type enzyme from HCT-116 cells, pH and temperature not specified in the publication
0.00013
SN-38
Homo sapiens
-
wild type enzyme from HT-29 cells, pH and temperature not specified in the publication
0.0034
SN-38
Homo sapiens
-
mutant enzyme R364K/G717R from HCT-116 cells, pH and temperature not specified in the publication
additional information
additional information
Homo sapiens
-
for a mixture of ethyl 5,12-dioxo-5,12-dihydroindolizino[2,3-g]isoquinoline-6-carboxylate and ethyl 5,12-dioxo-5,12-dihydroindolizino[3,2-g]isoquinoline-11-carboxylate the IC50 values are 0.00936 mM for GLC-82 cells, 0.01170 mM for MCF-7 cells, 0.0022 mM for NCI-H460 cells, and 0.01743 mM for HL-60 cells. For a mixture of 5,12-dioxo-5,12-dihydroindolizino[2,3-g]quinoline-6-carbonitrile and 5,12-dioxo-5,12-dihydroindolizino[3,2-g]quinoline-11-carbonitrile the IC50 values are 0.01267 mM for HL-60 cells, 0.00250 mM for GLC-82 cells, 0.00156 mM for MCF-7 cells, and 0.00016 mM for NCI-H460 cells
-
additional information
additional information
Homo sapiens
GI50 values (the concentrations corresponding to 50% growth inhibition) for the different inhibitors with the different cell lines listed
-
additional information
additional information
Homo sapiens
-
IC50 value for 11-methoxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione is more than 0.260 mM, for 1-hydroxy-8-methoxyanthracene-9,10-dione, 5,9,11-trimethoxy-2-methyl-4H-naphtho[2,3-h]chromene-4,7,12-trione, 11-methoxy-2-phenyl-4H-naphtho[2,3-h]chromene-4,7,12-trione and 1-[2-(dimethylamino)ethoxy]-8-methoxyanthracene-9,10-dione more than 0.100 mM
-
additional information
additional information
Homo sapiens
-
2-thienyl-4-furyl-6-aryl pyridine derivatives, IC50 values in cytotoxicity assays in cancer cell lines, overview
-
additional information
additional information
Homo sapiens
-
IC50 values of inhibitors in different cancer cell lines in vivo, effects after transient transfection, overview
-
additional information
additional information
Homo sapiens
-
inhibitor IC50 values in vivo in different cancer cell lines, overview
-
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H285A
-
display a low level of supercoil relaxation. Slow the rate of cleavage by a factor of 60 compared to the wild-type
R135A
-
form no detectable protein-DNA adduct during a 24 h incubation with the suicide substrate. The failure of this protein to relax supercoiled DNA is probably attributable to its inability to perform transesterification chemistry
R241A
-
form no detectable protein-DNA adduct during a 24 h incubation with the suicide substrate. The failure of this protein to relax supercoiled DNA is probably attributable to its inability to perform transesterification chemistry
Y294A
-
form no detectable protein-DNA adduct during a 24 h incubation with the suicide substrate. The failure of this protein to relax supercoiled DNA is probably attributable to its inability to perform transesterification chemistry
V617G
the mutant is resistant against topotecan
D113N
-
EcTOP, site-directed mutagenesis
D117N
-
site-directed mutagenesis, induction of mutant YpTOP1-D117N topoisomerase by arabinose is similar in the absence or presence of trimethoprim
G116S
-
EcTOP 67 kDa N-terminal fragment, site-directed mutagenesis
G194A
-
40fold reduction in relaxation activity when compared to wild-type enzyme, DNA cleavage activity is 100fold lower than that of the wild-type enzyme
G194R
-
no detectable relaxation activity and DNA cleavage
H365A
-
whereas wild type enzyme shows pH-dependent cleavage of oligonucleotides, cleavage by the mutant enzyme is pH-independent. Cleaves DNA with a slower rate than the wild-type enzyme, but can cleave more substrate overall, mutant enzyme has a lower DNA binding affinity than the wild-type enzyme, mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
H365D |
-
mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
H365E |
-
mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
H365N
-
mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
H365Q
-
whereas wild type enzyme shows pH-dependent cleavage of oligonucleotides, cleavage by the mutant enzyme is pH-independent. Cleaves DNA with rates similar to the wild-type enzyme, mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
H365R |
-
mutant shows a shift in maximal relaxation to above pH 8.5, mutant enzyme is less able than the wild type enzyme to relax negatively supercoiled DNA
K13A
-
Investigation of the potential catalytic role of the serine and lysine residue conserved in the active site region of bacterial topoisomerase I Ser10 and Lys13 of Escherichia coli DNA topoisomerase I are mutated to alanines. 50-to 100fold reduction in relaxation activity, not affected in non-covalent DNA binding, mutations at Ser10 and Lys13 highly reduce the ability of topoisomerase I to support growth of the Escherichia coli cells, as expected from the loss of the relaxation activity. Ala13 is unable to make interactions with the acidic residues of the active site. Side chains of Ser10 and Lys13 are required for DNA cleavage activity, rates of cleavage are too low to be analyzed
K13R
-
Arg13 residue is a larger residue than lysine, and is unable to fit in the space assigned to Lys13. Reduced DNA binding affinity, possibly changing Ser10 to a threonine residue, and changing Lys13 to arginine allow retention of activity, relaxation activity assays show that introduction of a different side chain with similar functionality but different steric properties at these two positions result in even lower relaxation activitymutations at Ser10 and Lys13 highly reduce the ability of topoisomerase I to support growth of the Escherichia coli cells, as expected from the loss of the relaxation activity. Do not have severe changes in protein folding. Side chains of Ser10 and Lys13 are required for DNA cleavage activity, rates of cleavage are too low to be analyzed
M320R
site-directed mutagenesis
R169
-
site-directed mutagenesis, the mutant shows reduced DNA cleavage and relaxation activity compared to the wild-type enzyme, the mutation to alanine changesd the selectivity of the enzyme for the base at the -4 position from a cytosine to an adenine
R173A
-
site-directed mutagenesis, the mutant displays similar sequence selectivity as the wild-type enzyme, but weaker cleavage and relaxation activity
R321F
-
site-directed mutagenesis, constants of oligonucleotide binding compared to the wild-type enzyme, the mutant shows reduced DNA cleavage and requirement for Mg2+
R321K
-
site-directed mutagenesis, constants of oligonucleotide binding compared to the wild-type enzyme, the mutant shows reduced DNA cleavage and requirement for Mg2+
R321L
-
site-directed mutagenesis, constants of oligonucleotide binding compared to the wild-type enzyme, the mutant shows reduced DNA cleavage and requirement for Mg2+
S10A
-
Investigation of the potential catalytic role of the serine and lysine residue conserved in the active site region of bacterial topoisomerase I Ser10 and Lys13 of Escherichia coli DNA topoisomerase I are mutated to alanines. 5-to 10fold reduction in relaxation activity, not affected in non-covalent DNA binding, mutations at Ser10 and Lys13 highly reduce the ability of topoisomerase I to support growth of the Escherichia coli cells, as expected from the loss of the relaxation activity. Ala10 is unable to form a hydrogen bond with phosphate 8. Side chains of Ser10 and Lys13 are required for DNA cleavage activity, yield of the cleaved complex observed is 30fold lower than the wild-type enzyme at each enzyme: substrate ratio even after 60 min of incubation
S10T
-
Reduced DNA binding affinity, possibly changing Ser10 to a threonine residue, and changing Lys13 to arginine allow retention of activity, relaxation activity assays show that introduction of a different side chain with similar functionality but different steric properties at these two positions result in even lower relaxation activitymutations at Ser10 and Lys13 highly reduce the ability of topoisomerase I to support growth of the Escherichia coli cells, as expected from the loss of the relaxation activity. Thr10 forms a hydrogen bond with phosphate 8. Do not have severe changes in protein folding. Side chains of Ser10 and Lys13 are required for DNA cleavage activity, rates of cleavage are too low to be analyzed
Y177A
-
site-directed mutagenesis, inactive mutant
Y177S
-
site-directed mutagenesis, inactive mutant
Y319F
-
site-directed mutagenesis, constants of oligonucleotide binding compared to the wild-type enzyme
D117N
-
site-directed mutagenesis, induction of mutant YpTOP1-D117N topoisomerase by arabinose is similar in the absence or presence of trimethoprim
-
A653P
-
known to be CPT resistant
Cropo4
-
chimeric enzyme, human topo I having residues 631-717 replaced by residues 314-317 of Cre
Cropo6
-
chimeric enzyme, human topo I having residues 631-717 replaced by residues 312-317 of Cre
Cropo8
-
chimeric enzyme, human topo I having residues 631-717 replaced by residues 312-319 of Cre
DELTA1-202
-
mutant enzyme is impaired in blunt end ligation but remains sensitive towards camptothecin in relaxation
DELTA191-206
-
mutant is distinguished from wild-type enzyme by a decreased relaxation rate at distributive and an increased rate under processive conditions. Mutant is strongly impaired in blunt end ligation and insensitive towards camptothecin in relaxation
E418K
-
the active site tyrosine. The Glu418Lys mutant is active and partially resistant to CPT in yeast cells expressed in yeast cells, display a camptothecin resistance that slowly decreases as a function of time
E710G
-
site-directed mutagenesis, the mutation is not detectable in tissue samples from colorectal cancer patients
F361S
camptothecin-resistant enzyme form
F617N
site-directed mutagenesis
G365C
-
camptothecin-resistant Top1(G365C) mutant
G622A
site-directed mutagenesis
G717D
-
the mutant enzyme is no more sensitive to camptothecin than the wild type enzyme
hTopoI (deltaNL)
-
hTopoI deletion mutant. Considering the domain organization, hTopoI distinguishes itself from both Vaccinia virus TopoI and the tyrosine recombinases, by having rather extensive N-terminal and linker domains. Investigation of the resolution activity of hTopoI deleted in either one or both of these domains. Two hTopoI variants, hTopoI(deltaN) lacking aa 1-202, and hTopoI(deltaNL) lacking aa 1-202 and 660-688. Deleting the N-terminal and linker domains of hTopoI in order to mimic the domain organization of Vaccinia virus TopoI and the tyrosine recombinases inhibited resolution of the Holliday junction substrate. hTopoI(deltaNL) forms dimers
hTopoI(deltaN)
-
hTopoI deletion mutant. Considering the domain organization, hTopoI distinguishes itself from both Vaccinia virus TopoI and the tyrosine recombinases, by having rather extensive N-terminal and linker domains. Investigation of the resolution activity of hTopoI deleted in either one or both of these domains. Two hTopoI variants, hTopoI(deltaN) lacking aa 1-202, and hTopoI(deltaNL) lacking aa 1-202 and 660-688. Deleting the N-terminal and linker domains of hTopoI in order to mimic the domain organization of Vaccinia virus TopoI and the tyrosine recombinases inhibited resolution of the Holliday junction substrate. hTopoI(deltaNL) forms dimers
I623V
site-directed mutagenesis
K532R
cleavage and religation activity of the mutant enzyme are reduced, cleavage is reduced to a greater extent than religation
K550Q
site-directed mutagenesis
K605Q
site-directed mutagenesis
K616M
site-directed mutagenesis
K616Q
site-directed mutagenesis
K616R
site-directed mutagenesis
K681A
-
site-directed mutagenesis, the mutation of Lys681, located on the tip of the linker domain, dramatically reduces the religation rate, the equilibrium of the mutant is shifted toward cleavage when compared to the wild-type enzyme. Mutation of residue 681 from lysine to alanine does not cause alterations in the linker domain secondary structure, and the main chain conformation of the mutated residue does not significantly change in relation with the neighbor residues, when compared to the wild-type protein
L603V
site-directed mutagenesis
L617I
-
site-directed mutagenesis, the mutation is not detectable in tissue samples from colorectal cancer patients
M621I
site-directed mutagenesis
M621S
site-directed mutagenesis
N618S
site-directed mutagenesis
N722S
camptothecin-resistant enzyme form, mutation leads to elimination of a water-mediated contact between the enzyme and topotecan
Q613R
site-directed mutagenesis
R364K/G717R
-
the mutations lead to resistance towards inhibitors SN-38 and NSC 743400
R621H
-
site-directed mutagenesis, the mutation is not detectable in tissue samples from colorectal cancer patients
S10A/S112A/S394A
-
triple mutant 3A
S10A/S21A/S112A/S394A
-
quadruple phosphomutant 4A
S21A
-
site-directed mutagenesis
T729A
-
mutations that confer camptothecin resistance, but do not interact directly with the drug or the DNA, oligonucleotide-directed mutagenesis
T729E
-
camptothecin resistance, remarkable defect in DNA binding, oligonucleotide-directed mutagenesis
W203A/W205A/W206A
lacking processivity, exhibits resistance to camptothecin and is inactivated by urea. Indicates that the tryptophan anchor stabilizes the N-terminus of the functional domain and revents the loss of Top1 structure and function
W205G
-
mutant is distinguished from wild-type enzyme by a decreased relaxation rate at distributive and an increased rate under processive conditions. Mutant is strongly impaired in blunt end ligation and insensitive towards camptothecin in relaxation
Y337F
-
mutant enzyme is still able to bind single-stranded DNA but is unable to cleave the DNA substrate because of the absence of the active Tyr337
Y552N
site-directed mutagenesis
Y612N
site-directed mutagenesis
Y727F
catalytically inactive
D325E
-
substantial level of resistance to camptothecin, 50% inhibition at 0.01 mM
delta 175-262
-
N-terminal truncation performed on LdTop1S subunits
delta 180-262
-
N-terminal truncation performed on LdTop1S subunits
delta 182-262
-
N-terminal truncation performed on LdTop1S subunits
delta 200-262
-
N-terminal truncation performed on LdTop1S subunits
delta 210-262
-
N-terminal truncation performed on LdTop1S subunits
delta 39-635
-
in contrast to camptothecin, baicalein and luteolin fail to inhibit the religation step when the drugs are added to pre-formed enzyme substrate binary complex. This differential mechanism to induce the stabilization of cleavable complex with topoisomerase I and DNA by these selected flavones and camptothecin result in investigations of the effect of baicalein and luteolin on camptothecin-resistant mutant enzyme LdTOP1D39LS lacking 139 amino acids of the large subunit
G185R
-
substantial level of resistance to camptothecin, 50% inhibition at 0.035 mM
G185R/D325
-
parasites containing both mutations simultaneously show high level of resistance to camptothecin
G185R/D325E
-
highly camptothecin-resistant with two substitutions in the core domain of the protein
H453A
-
Very little relaxing activity detectable, activity of the H453A protein to be more than 100fold reduced compared with that of LdTOPIL-fus-S
H453Q
-
Lower activity than LdTOPIL-fus-S, failing to completely relax the supercoiled DNA even after 40 min
K352A
-
site-directed mutagenesis, the mutant shows highly reduced relaxation activity compared to wild-type enzyme, the cleavage religation equilibrium is shifted towards the cleavage
K352R
-
site-directed mutagenesis, the mutant shows highly reduced relaxation activity compared to wild-type enzyme, the cleavage religation equilibrium is shifted towards the cleavage
R314K
-
site-directed mutagenesis, the mutant shows onyl slightly affected relaxation activity and only a slightly slower rate of cleavage compared to wild-type enzyme
D261A LdTOPIS
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
GST-LdTOPIS delta 1-201
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 1-210
-
constitute the minimal interacting fragment. Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 1-210/delta 255-262
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 1-215
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 1-80
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 245-262
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
GST-LdTOPIS delta 255-262
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
K243A LdTOPIS
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
K436A LdTOPIL
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
K455A LdTOPIL
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
LdTOPIL delta 1-39
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
LdTOPIL delta 1-39/delta457-635
-
constitute the minimal interacting fragment. Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
LdTOPIL delta 1-99
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
LdTOPIL delta 436-635
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
LdTOPIL delta 457-635
-
Generated N-and C-terminal-truncated deletion constructs of of L and S subunit. The heterodimerization between the two fragments is weak and therefore co-purified fragments show reduced DNA binding, cleavage and relaxation properties compared with the wild type enzyme
N256A LdTOPIS
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
N441A LdTOPIL
-
Site-directed mutagenesis studies identify Lys455 of LdTOPIL and Asp261 of LdTOPIS as two residues involved in subunit interaction. The reconstituted mutant enzymes LdTOPILK436A/S, LdTOPILN441A/S, L/LdTOPISK249A and L/LdTOPISN256A do not show any appreciable change in the relaxation pattern compared with the wild-type enzyme L/S. Reconstitution of L with LdTOPISD261A (SD261A) causes a 15fold decrease in the relaxation activity compared with L/S
E215A
-
mutant activity with the mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V) is active over a wider range of pH values, compared with wild-type enzyme. Mutant activity with the mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V) is active over a wider range of pH values, compared with wild-type enzyme
E215H
-
mutant enzyme is active over a wider range of pH values, compared with wild-type enzyme, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
E215Q
-
mutant enzyme is active over a wider range of pH values, compared with wild-type enzyme, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
E215R
-
mutant enzyme is active over a wider range of pH values, compared with wild-type enzyme, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
H200A
-
mutant enzyme is slightly less active than wild type enzyme, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
H200E
-
mutant has low but detectable DNA relaxation activity at pH 5, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
H200N
-
mutant enzyme is slightly less active than wild type enzyme, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
H200Q
-
mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
H200R
-
mutant enzyme shows relaxation activity over a pH range similar to the wild-type enzyme. In the Topo-78 backbone (an N-terminal 78-kDa fragment of Topo-V), qualitatively, H200R is as active as the wild type
K128R
-
mutant enzyme shows very minimal activity at pH 8
K218Q
-
the mutant is inactive in all of the pH conditions tested, mutation in the Topo-78 fragment (an N-terminal 78-kDa fragment of Topo-V)
R131A
-
mutant shows no detectable DNA relaxation activity, mutations in Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V) or in Topo-78 fragment (an N-terminal 78-kDa fragment of Topo-V)
R131K
-
conservative substitution that retains both the electrostatic and acid/base properties, except for the loss of the bidentate coordination possible through the guanidinium group of the arginine. Whereas the R131K mutant is purified successfully in the Topo-44 backbone, it results in degradation when expressed in the Topo-78 backbone
R144A
-
mutant enzyme shows no activity, mutation in Topo-78 fragment (an N-terminal 78-kDa fragment of Topo-V)
T226F
-
the mutation abolishes activity at all pH values in T44Y226F and shows only minimal activity at pH 8, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
Y226F
-
mutation abolishes DNA binding, mutation in the Topo-44 fragment (an N-terminal 44-kDa fragment of Topo-V)
D111A
site-directed mutagenesis, mutation of the Mg2+-binding residue affects DNA relaxation activity, mutant D111A is dependent on Mg2+ for DNA cleavage and is compromised in religation
D111N
-
site-directed mutagenesis, the mutation is lethal for the host
D113A
site-directed mutagenesis
E115A
site-directed mutagenesis, mutation of the Mg2+-binding residue affects DNA relaxation activity, the mutant is compromised in religation
G116S
-
site-directed mutagenesis, MtTOP1 TOPRIM motif mutation, the mutation inhibits DNA religation. The DNA cleavage activity of MtTOP1-G116 S is Mg2+-dependent
H139C
-
site-directed mutagenesis, the mutant can be labeled with fluorophores with no significant loss of relaxation activity, the mutant complements the temperature sensitive topA function of Escherichia coli strain AS17
K524C
-
site-directed mutagenesis, the mutant can be labeled with fluorophores with no significant loss of relaxation activity, the mutant complements the temperature sensitive topA function of Escherichia coli strain AS17
L170C
-
site-directed mutagenesis, the mutant can be labeled with fluorophores with no significant loss of relaxation activity, the mutant complements the temperature sensitive topA function of Escherichia coli strain AS17
T142C
-
site-directed mutagenesis, the mutant can be labeled with fluorophores with no significant loss of relaxation activity, the mutant complements the temperature sensitive topA function of Escherichia coli strain AS17
Y174C
-
site-directed mutagenesis, the mutant can be labeled with fluorophores with no significant loss of relaxation activity, the mutant complements the temperature sensitive topA function of Escherichia coli strain AS17
D111A
-
site-directed mutagenesis, mutation of the Mg2+-binding residue affects DNA relaxation activity, mutant D111A is dependent on Mg2+ for DNA cleavage and is compromised in religation
-
D113A
-
site-directed mutagenesis
-
E115A
-
site-directed mutagenesis, mutation of the Mg2+-binding residue affects DNA relaxation activity, the mutant is compromised in religation
-
I420V
-
prepared by PCR-based mutagenesis
L530I
-
prepared by PCR-based mutagenesis
N421K
-
prepared by PCR-based mutagenesis
N722S
-
prepared by PCR-based mutagenesis
D710G
-
the mutant is resistant against topotecan
G721D
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721E
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721F
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721L
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721N
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721Q
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
G721V
-
Single amino acid substitutions of yeast Gly721 alters Top1p sensitivity to camptothecin
L720E
-
Single amino acid substitutions of Leu720 alters Top1p sensitivity to camptothecin
L720Q
-
Single amino acid substitutions of Leu720 alters Top1p sensitivity to camptothecin
N726F
-
specific activity is about 5fold lower than that of wild-type enzyme, self-poisoning phenotype, mutation enhances the kinetics of DNA cleavage
N726H
-
self-poisoning phenotype, specific activity is about 5fold lower than that of wild-type enzyme, binding of DNA increases from 2.5fold at 50 mM KCl to 4fold at 100 mM KCl, 10fold increase in DNA cleavage activity
N726K
-
camptothecin resistance of cells expressing the mutant enzyme
N726Q
-
camptothecin resistance of cells expressing the mutant enzyme
N726S
-
mutant enzyme is resistant to camptothecin
N726Y
-
mutation enhances the kinetics of DNA cleavage
T722A
-
self-poisoning phenotype, reduced rate of DNA religation relative to wild-type enzyme, specific activity of the mutant enzyme is slightly decreased, however protein binding of DNA and rates of enzyme-catalyzed
T722A/N726H
-
specific activity is about 5fold lower than that of wild-type enzyme, N726H mutation potentiates the cytotoxic activity of T722A, increase in DNA cleavage activity
C559A/C561A
no detectable zinc is bound to the mutant enzyme and its fluorescence properties are modified, suggesting a change of conformation in the protein lacking zinc. GThe mutant enzyme exhibits an activity similar to that of the wild-type enzyme with the same optimal temperature for activity. Thermostability is not affected by the mutation. Decatenase activity of wild type and C559A/C561A mutant enzymes shows no significant difference. Cleavage positions obtained with the C559A/C561A mutant is similar to those observed with the wild type enzyme. Preference for cytosine at position -4 is retained, and cleavage intensities are comparable
Y288F
totally inactive protein
C559A/C561A
-
no detectable zinc is bound to the mutant enzyme and its fluorescence properties are modified, suggesting a change of conformation in the protein lacking zinc. GThe mutant enzyme exhibits an activity similar to that of the wild-type enzyme with the same optimal temperature for activity. Thermostability is not affected by the mutation. Decatenase activity of wild type and C559A/C561A mutant enzymes shows no significant difference. Cleavage positions obtained with the C559A/C561A mutant is similar to those observed with the wild type enzyme. Preference for cytosine at position -4 is retained, and cleavage intensities are comparable
-
Y288F
-
totally inactive protein
-
D298A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
E124A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
E299A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
F101A
-
mutant enzyme displayes an aberrant response to magnesium, rate of relaxation is lower by a factor of 4-5 in the presence of 5 mM magnesium than in its absence, the rate of relaxation in presence of NaCl plus magnesium is reduced by a factor of 10.20 compared to wild-type enzyme, affinity for 60-bp duplex is 8fold lower than that of wild-type enzyme
F297A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
F88A
-
mutant enzyme displayes an aberrant response to magnesium, rate of relaxation is lower by a factor of 4-5 in the presence of 5 mM magnesium than in its absence, the rate of relaxation in presence of NaCl plus magnesium is reduced by a factor of 10-20 compared to wild-type enzyme, affinity for 60-bp duplex is 3fold lower than that of wild-type enzyme
K104A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
K107A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
K108A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
K220A
-
supercoil relaxation by mutant enzyme in presence of NaCl and no divalent cation is slower by a factor of 5 than relaxation by wild-type enzyme, mutant enzyme is inhibited by including Mg2+ with NaCl, rate of relaxation in presence of NaCl plus Mg2+ is reduced by 20fold compared to wild-type enzyme
K220H
-
supercoil relaxation by mutant enzyme in presence of NaCl and no divalent cation is slower by a factor of 5 than relaxation by wild-type enzyme, mutant enzyme is inhibited by including Mg2+ with NaCl, rate of relaxation in presence of NaCl plus Mg2+ is reduced by 40fold compared to wild-type enzyme
K220Q
-
supercoil relaxation by mutant enzyme in presence of NaCl and no divalent cation is slower by a factor of 5 than relaxation by wild-type enzyme, mutant enzyme is inhibited by including Mg2+ with NaCl, rate of relaxation in presence of NaCl plus Mg2+ is reduced by 40fold compared to wild-type enzyme
K220R
-
supercoil relaxation by mutant enzyme in presence of NaCl and no divalent cation is slower by a factor of 2 than relaxation by wild-type enzyme, neither stimulated nor inhibited by Mg2+, rate of relaxation in presence of NaCl plus Mg2+ is reduced by 8fold compared to wild-type enzyme
N103A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
N228A
-
relaxation of supercoiled DNA in presence of NaCl and no divalent cation is slower by a factor of 8 than relaxation by the wild-type enzyme
N228D
-
relaxation of supercoiled DNA in presence of NaCl and no divalent cation is slower by a factor of 40 than relaxation by the wild-type enzyme, mutant enzyme is inhibited by Mg2+, oligonucleotide cleavage is slower than that of wild-type enzyme by a factor of 200
N228Q
-
relaxation of supercoiled DNA in presence of NaCl and no divalent cation is slower by a factor of 5 than relaxation by the wild-type enzyme, not stimulated by including magnesium with NaCl
N228S
-
relaxation of supercoiled DNA in presence of NaCl and no divalent cation is slower by a factor of 2 than relaxation by the wild-type enzyme
N99A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
Q116A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
R90A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
R97A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
S204A
-
mutant protein relaxes supercoiled DNA slowly and is strongly inhibited in the presence of salt plus magnesium, the rate of single-turnover religation by covalently bound S204N is indistinguishable from wild-type within the limits of the assay
T296A
-
relaxation rate is equivalent to that of the wild-type enzyme in absence and presence of Mg2+
Y274F
-
vaccinia topoisomerase mutant, lacks active site tyrosine nucleophile but binds to DNA containing specific recognition sequence, like wild type vTopo
A383P
-
mutant enzyme has wild-type levels of relaxation and cleavage activity
C737Y
Q7CIL8
site-directed mutagenesis
D116N/W866L
Q7CIL8
site-directed mutagenesis
D117N
Q7CIL8
site-directed mutagenesis
D117N/C608G
Q7CIL8
site-directed mutagenesis
D117N/C668F
Q7CIL8
site-directed mutagenesis
D117N/C737Y
Q7CIL8
site-directed mutagenesis
D119N
Q7CIL8
site-directed mutagenesis
D80N/G94S/D117N
Q7CIL8
YpTOP39 has D80N, G94S, and D117N mutations
E121Q
Q7CIL8
site-directed mutagenesis
G116S
-
mutant enzyme shows more than 400fold loss of relaxation activity
M326D
-
substitution mutant
M326E
-
substitution mutant
M326K
-
substitution mutant
M326P
-
substitution mutant
M326R
-
overexpression of the M326R mutant YTOP resulted in 4 log loss of viability
M326S
-
substitution mutant
M326T
-
substitution mutant
M326V
-
mutant enzyme has wild-type levels of relaxation and cleavage activity
R327F
-
site-directed mutagenesis, the mutation leads to the SOS response and has a strong cell killing effect when the mutant is overexpressed in Escherichia coli and induced with 0.2% arabinose, the mutant shows reduced DNA cleavage and requirement for Mg2+
R327I
-
site-directed mutagenesis, the mutation leads to the SOS response and has a strong cell killing effect when the mutant is overexpressed in Escherichia coli and induced with 0.2% arabinose, the mutant shows reduced DNA cleavage and requirement for Mg2+
R327L
-
site-directed mutagenesis, the mutation leads to the SOS response and has a strong cell killing effect when the mutant is overexpressed in Escherichia coli and induced with 0.2% arabinose, the mutant shows reduced DNA cleavage and requirement for Mg2+
R327W
-
site-directed mutagenesis, the mutation leads to the SOS response and has a strong cell killing effect when the mutant is overexpressed in Escherichia coli and induced with 0.2% arabinose, the mutant shows reduced DNA cleavage and requirement for Mg2+
T265M
-
site-directed mutagenesis, the mutant does not show a phenotype
V559I
-
site-directed mutagenesis, the mutant does not show a phenotype
D111N
-
EcTOP 67 kDa N-terminal fragment, site-directed mutagenesis
D111N
-
site-directed mutagenesis, the mutant is trapped in complex with DNA, accumulation of the covalent complex of bacterial topoisomerase I is lethal. A full-length enzyme with this D111N mutation could not be expressed, but the N-terminal 67-kDa transesterification domain. Structure comparison of wild-type and D111N mutant enzymes, overview
K532A
cleavage and religation activity of the mutant enzyme are reduced, religation is reduced to a greater extent than cleavage
K532A
expression of the mutant enzyme in Saccharomyces cerevisiae is cytotoxic, this mutant enzyme mimics the effects of the anticancer drug camptothecin
T729K
-
camptothecin resistance, oligonucleotide-directed mutagenesis
T729K
is resistant even at high concentration to camptothecin anti-cancer drug
T729P
-
oligonucleotide-directed mutagenesis
T729P
mild reduction in drug sensitivity and in DNA binding
Y723F
-
site-directed mutagenesis
Y723F
site-directed mutagenesis
Y723F
mutation renders the topoisomerase completely inactive
Y723F
-
catalytically inactive TOP1(Y723F)
Y723F
-
the active site mutant shows abolished formation of Top1 covalent adducts with DNA structures
Y327F
site-directed mutagenesis, the active site mutant construct cannot suppress the slow-growth of top3 mutant Saccharomyces cerevisiae
Y327F
-
site-directed mutagenesis, the active site mutant construct cannot suppress the slow-growth of top3 mutant Saccharomyces cerevisiae
-
N726D
-
mutant enzyme is resistant to camptothecin, no appreciable decrease in catalytic activity, exhibits a distributive mode of plasmid DNA relaxation compared to a progressive mode of the wild-type enzyme. Activity of the mutant enzyme is optimal at 75-100 mM KCl, compared to 150 mM KCl for the wild-type enzyme
N726D
-
self-poisoning phenotype, reduced rate of DNA religation relative to wild-type enzyme, affinity for DNA is reduced about 2.5fold relative to that observed for wild-type Top1p at 50 or 75 mM KCl
Y727F
-
catalytically inactive
Y727F
-
inactive mutant enzyme
Y727F
-
inactive Top1p mutant
Y727F
-
catalytically inactive
-
G122S
Q7CIL8
site-directed mutagenesis
G122S
-
mutant enzyme shows more than 400fold loss of relaxation activity
R327S
-
naturally occuring mutation identified in the AW3-75 mutant, the mutation leads to the SOS response and has a cell killing effect when the mutant is overexpressed in Escherichia coli and induced with 0.2% arabinose
R327S
-
site-directed mutagenesis, the mutant does not show a phenotype
additional information
-
conclude that the active sites of MimiTopIB and vaccinia TopIB are composed of similar functional groups
additional information
An experiment was performed to assess the ability of bcTopo IIIbeta to substitute for ecTopo III in vivo. bcTopo IIIbeta can not substitute for the loss of ecTopo III in Escherichia coli
additional information
-
An experiment was performed to assess the ability of bcTopo IIIbeta to substitute for ecTopo III in vivo. bcTopo IIIbeta can not substitute for the loss of ecTopo III in Escherichia coli
additional information
-
An experiment was performed to assess the ability of bcTopo IIIbeta to substitute for ecTopo III in vivo. bcTopo IIIbeta can not substitute for the loss of ecTopo III in Escherichia coli
-
additional information
comparison of wild-type Escherichia coli topoisomerase III with the Escherichia coli topoisomerase III (Y328F) mutant. Conformational differences: the ssDNA is not as deeply buried in the active site of the open complexes as it is in the topoisomerase IIIY328F+ ssDNA complex. EnzymeDNA interactions along the binding groove in the fully bound wild-type-DNA complex are analogous to those seen in the topoisomerase IIIY328F-DNA structure. Conformation resembles the one observed previously with a DNA-bound, catalytically inactive mutant of topoisomerase III where DNA binding realigns catalytic residues to form a functional active site
additional information
-
comparison of wild-type Escherichia coli topoisomerase III with the Escherichia coli topoisomerase III (Y328F) mutant. Conformational differences: the ssDNA is not as deeply buried in the active site of the open complexes as it is in the topoisomerase IIIY328F+ ssDNA complex. EnzymeDNA interactions along the binding groove in the fully bound wild-type-DNA complex are analogous to those seen in the topoisomerase IIIY328F-DNA structure. Conformation resembles the one observed previously with a DNA-bound, catalytically inactive mutant of topoisomerase III where DNA binding realigns catalytic residues to form a functional active site
additional information
-
expression of His-tagged Yersinia pestis topoisomerase I mutants, that are deficiency in DNA rejoining, under the control of the BAD promoter in plasmid pYTOP in Escherichia coli strain JD5 and purification by nickel affinity chromatography leading to a lethal phenotype of the Escherichia coli cells, overview
additional information
-
dissociation constants obtained for binding of wild-type EcTOP1, R169A, R173A and Y177S mutant enzymes to 3'-labeled 59 base hairpin oligonucleotide substrates, Oligo C, Oligo A and Oligo G, overview
additional information
-
preparation of YrdD protein, the homologue of the topoisomerase I C-terminal region, that contains only iron or zinc by expressing the protein in Escherichia coli cells grown in the M9 minimal media supplemented with either iron or zinc, respectively
additional information
-
usage of isogenic topA+ strain RFM44526 to study the involvement of topoisomerase I function in the SOS response. To monitor the extent of cell killing from accumulation of the topoisomerase I cleavage complex, Escherichia coli strain BW117N with a mutant Yersinia pestis topoisomerase I, YpTOP1-D117N, gene under the control of the BAD promoter inserted into the chromosome36 is used
additional information
-
usage of isogenic topA+ strain RFM44526 to study the involvement of topoisomerase I function in the SOS response. To monitor the extent of cell killing from accumulation of the topoisomerase I cleavage complex, Escherichia coli strain BW117N with a mutant Yersinia pestis topoisomerase I, YpTOP1-D117N, gene under the control of the BAD promoter inserted into the chromosome36 is used
-
additional information
molecular models of human topoisomerase I bearing K532-PL, K532-PLP and K532-PLP-AMP modified residues build with the molecular modelling package Insight II
additional information
-
molecular models of human topoisomerase I bearing K532-PL, K532-PLP and K532-PLP-AMP modified residues build with the molecular modelling package Insight II
additional information
-
Topoisomerase I is modified at the active site by incorporation of a number of tyrosine analogues employed 13 structural analogous of tyrosine. SDS-PAGE, in vitro synthesis of human topoisomerase I analogues modified at position 723. Human topoisomerase I-mediated DNA relaxation assay
additional information
-
p53-/- cell, p53-null variant of HCT116 cells
additional information
plasmid constructs used: pTop65 has an initiator methionine codon followed by Top1 codons 214-765, pTop68 has an initiator methionine codon followed by six histidine codons and four codons encoding the Factor Xa protease-cleavage site, and then Top1 codons 201-765, pTop68W/A is the same as pTop68 except that Trp203, Trp205 and Trp206 are mutated to alanine, pTop69NLS has an initiator methionine codon followed by six histidine codons and four codons encoding the Factor Xa protease-cleavage site, and then Top1 codons 189-765
additional information
-
plasmid constructs used: pTop65 has an initiator methionine codon followed by Top1 codons 214-765, pTop68 has an initiator methionine codon followed by six histidine codons and four codons encoding the Factor Xa protease-cleavage site, and then Top1 codons 201-765, pTop68W/A is the same as pTop68 except that Trp203, Trp205 and Trp206 are mutated to alanine, pTop69NLS has an initiator methionine codon followed by six histidine codons and four codons encoding the Factor Xa protease-cleavage site, and then Top1 codons 189-765
additional information
-
enzyme downregulation by topoisomerase I siRNA in HeLa cells
additional information
-
expression of specific siRNA inhibits the enzyme and elicits distinct changes in TF biosynthesis in TNF-alpha-stimulated endothelial cells, which impact endothelial procoagulant activity
additional information
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generation of mutant cells that are deficient in mitochondrial isozyme Top1mt, i.e. the Top1mt-/- cell line
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in vitro gene fusion of Leishmania bisubunit topoisomerase I into a single ORF encoding a new monomeric topoisomerase I (LdTOPIL-fus-S), N-terminal truncation mutant (1210 amino acids) of the small subunit, when fused to the intact large subunit [LdTOPIL-fus-D(1210)S], shows reduced topoisomerase I activity and camptothecin sensitivity in comparison to LdTOPIL-fus-S experiments in which Leishmania bisubunit topoisomerase I large subunit (LdTOPIL) and small subunit (LdTOPIS) genes are fused into a single ORF encoding a new topoisomerase I (LdTOPIL-fus-S), suicidal cleavage activity and religation activity of LdTOPIL-fus-S and its mutant variants
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Leishmania donovani strain Ld160CPTR camptothecin-resistant Leishmania donovani strain. The camptothecin-resistant strain reached a resistance level of 32fold over the wild-type Leishmania donovani AG83 strain. Baicalein and luteolin show inhibition of relaxation activity up to 60% at 30 mM concentration compared with that of camptothecin, where no inhibition of relaxationactivity is observed
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three truncated Topo V polypeptides comprising the NH2-terminal 44000 Da and 16000 Da domains, the 44000 Da, 16000 Da and 18000 Da domains and the C-terminal 34000 Da domain. Topo61 and Topo78 are active topoisomerases, but in contrast to Topo V these enzymes are inhibited by high salt concentrations. Topo34 has strong DNA-binding ability but shows no topoisomerase activity. Topo78 and Topi34 possess apurinic/apyrimidinic lyase activity that is important in base excision DNA repair
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preparation of several mutant mTopoI promoters, including wild type and E1, E2, Dbox, E1/Dbox, E1/E2, and E1/E2/Dbox mutant types, and measurement of bioluminescence using a real-time monitoring assay
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preparation of several mutant mTopoI promoters, including wild type and E1, E2, Dbox, E1/Dbox, E1/E2, and E1/E2/Dbox mutant types, and measurement of bioluminescence using a real-time monitoring assay
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the His6 tagged-MtbTopA protein is immobilized on an NTA chip. When an increasing amount of GST tagged-Rv2436 protein pass over the chip, they cause a substantial response, overview
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the His6 tagged-MtbTopA protein is immobilized on an NTA chip. When an increasing amount of GST tagged-Rv2436 protein pass over the chip, they cause a substantial response, overview
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the His6 tagged-MtbTopA protein is immobilized on an NTA chip. When an increasing amount of GST tagged-Rv2436 protein pass over the chip, they cause a substantial response, overview
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generation of deletion mutants of the enzyme lacking each one of the three basic stretches of the C-terminal domain. The mutants are highly compromised in binding two DNA molecules
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TopA depletion in strains PS01 (wild-type background) and PS03 (-parB background). TopA depletion in the -parB background (PS03) leads to a decrease in chromosome segregation abnormalities with 8.9% anucleate prespores compared to that in the parB deletion strain J3305, with 19.5% anucleate prespores
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modification of vaccinia topoisomerase I at the active site tyrosine (position 274) with several tyrosine analogues. These analogues have varied steric, electronic, and stereochemical features to permit assessment of those structural elements required to support topoisomerase function. Eleven tyrosine analogues are successfully incorporated into the active site of vaccinia topoisomerase I. It is found that only tyrosine analogues having the phenolic -OH group in the normal position relative to the protein backbone are active. Modifications that replace the nucleophilic tyrosine OH group with NH2, SH, or I groups or that changed the orientation of the nucleophilic OH group essentially eliminate topoisomerase I function
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