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Literature summary for 3.4.23.B24 extracted from

  • Velcicky, J.; Bodendorf, U.; Rigollier, P.; Epple, R.; Beisner, D.R.; Guerini, D.; Smith, P.; Liu, B.; Feifel, R.; Wipfli, P.; Aichholz, R.; Couttet, P.; Dix, I.; Widmer, T.; Wen, B.; Brandl, T.
    Discovery of the first potent, selective, and orally bioavailable signal peptide peptidase-like 2a (SPPL2a) inhibitor displaying pronounced immunomodulatory effects in vivo (2018), J. Med. Chem., 61, 865-880 .
    View publication on PubMed
Search for more literature for 3.4.23.B24

Cloned(Commentary)

Cloned (Comment) Organism
gene SPPL2a, recombinant expression in U-2 OS cells Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(2R)-2-methyl-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]-N4-[2-(trifluoromethyl)phenyl]butanediamide
-
 Homo sapiens
(2R)-2-methyl-N4-(2-methylphenyl)-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide reversible, inhibits CD74/p8 processing in vivo and spares gamma-secretase activity Homo sapiens
(2R)-2-methyl-N4-(2-methylphenyl)-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
-
 Mus musculus
(2R)-2-methyl-N4-(2-methylphenyl)-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
-
 Rattus norvegicus
(2R)-2-methyl-N4-(2-methylpyridin-3-yl)-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
-
 Homo sapiens
(2R)-2-methyl-N4-(3-methylphenyl)-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
-
 Homo sapiens
(2R)-2-methyl-N4-(4-methylphenyl)-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
-
 Homo sapiens
(2R)-N1-[(10S)-5,11-dioxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]-N4-(5-fluoro-2-methylpyridin-3-yl)-2-methylbutanediamide
-
 Homo sapiens
(2R)-N4-(3,5-difluorophenyl)-2-methyl-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
-
 Homo sapiens
(2R)-N4-(5-fluoro-2-methylpyridin-3-yl)-2-methyl-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
-
 Homo sapiens
(2R)-N4-(5-fluoro-2-methylpyridin-3-yl)-2-methyl-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
-
 Mus musculus
(2R)-N4-(5-fluoro-2-methylpyridin-3-yl)-2-methyl-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
-
 Rattus norvegicus
(2R)-N4-(5-fluoro-2-methylpyridin-3-yl)-N1-[(10S)-6-fluoro-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]-2-methylbutanediamide
-
 Homo sapiens
(2R)-N4-(5-fluoro-2-methylpyridin-3-yl)-N1-[(10S)-6-fluoro-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]-2-methylbutanediamide
-
 Rattus norvegicus
(2S)-2-cyclopropyl-N1-[(10'S)-5',11'-dioxo-10',11'-dihydro-1'H,3'H,5'H-spiro[cyclopropane-1,2'-pyrazolo[1,2-b][2,3]benzodiazepin]-10'-yl]-N4-(5-fluoro-2-methylpyridin-3-yl)butanediamide
-
 Mus musculus
(2S)-2-cyclopropyl-N1-[(10'S)-5',11'-dioxo-10',11'-dihydro-5'H-spiro[cyclopropane-1,2'-pyrazolo[1,2-b][2,3]benzodiazepin]-10'-yl]-N4-(5-fluoro-2-methylpyridin-3-yl)butanediamide
-
 Homo sapiens
(2S)-2-cyclopropyl-N1-[(10'S)-5',11'-dioxo-10',11'-dihydro-5'H-spiro[cyclopropane-1,2'-pyrazolo[1,2-b][2,3]benzodiazepin]-10'-yl]-N4-(5-fluoro-2-methylpyridin-3-yl)butanediamide
-
 Mus musculus
(2S)-2-cyclopropyl-N1-[(10'S)-5',11'-dioxo-10',11'-dihydro-5'H-spiro[cyclopropane-1,2'-pyrazolo[1,2-b][2,3]benzodiazepin]-10'-yl]-N4-(5-fluoro-2-methylpyridin-3-yl)butanediamide
-
 Rattus norvegicus
(2S)-2-cyclopropyl-N1-[(10S)-5,11-dioxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]-N4-(5-fluoro-2-methylpyridin-3-yl)butanediamide
-
 Homo sapiens
2,2'-(2-oxo-1,3-propanediyl)bis[N-[(phenylmethoxy)carbonyl]-L-leucyl-L-leucinamide] (Z-LL)2-ketone Homo sapiens
2,2'-(2-oxo-1,3-propanediyl)bis[N-[(phenylmethoxy)carbonyl]-L-leucyl-L-leucinamide] (Z-LL)2-ketone Mus musculus
2,2'-(2-oxo-1,3-propanediyl)bis[N-[(phenylmethoxy)carbonyl]-L-leucyl-L-leucinamide] (Z-LL)2-ketone Rattus norvegicus
LY-411,575
-
 Homo sapiens
LY-411,575
-
 Mus musculus
LY-411,575
-
 Rattus norvegicus
LY-411575 N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide Mus musculus
additional information development and synthesis of potent, selective, and orally bioavailable signal peptide peptidase-like 2a (SPPL2a) inhibitors displaying pronounced immunomodulatory effects in vivo. Selectivity of inhibitors for SPP compared to gamma-secretase, overview Homo sapiens
additional information development and synthesis of potent, selective, and orally bioavailable signal peptide peptidase-like 2a (SPPL2a) inhibitor displaying pronounced immunomodulatory effects in vivo. Selectivity of inhibitors for SPP compared to gamma-secretase, overview Mus musculus
additional information development and synthesis of potent, selective, and orally bioavailable signal peptide peptidase-like 2a (SPPL2a) inhibitor displaying pronounced immunomodulatory effects in vivo. Seletivity of inhibitors for SPP compared to gamma-secretase, overview Rattus norvegicus

Localization

Localization Comment Organism GeneOntology No. Textmining
microsome
-
 Mus musculus
-
-
microsome
-
 Homo sapiens
-
-
microsome
-
 Rattus norvegicus
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
CD74/p8 + H2O Homo sapiens
-
 ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q8TCT8
-
-
Mus musculus Q9JJF9
-
-
Rattus norvegicus D3ZNG3
-
-

Source Tissue

Source Tissue Comment Organism Textmining
B-lymphocyte
-
 Homo sapiens
-
B-lymphocyte
-
 Rattus norvegicus
-
B-lymphocyte B-cell line A20 Mus musculus
-
dendritic cell
-
 Mus musculus
-
dendritic cell
-
 Homo sapiens
-
dendritic cell
-
 Rattus norvegicus
-
HEK-293 cell
-
 Homo sapiens
-
liver
-
 Mus musculus
-
liver
-
 Homo sapiens
-
liver
-
 Rattus norvegicus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
CD74/p8 + H2O
-
 Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
aspartic intramembrane protease
-
 Mus musculus
aspartic intramembrane protease
-
 Homo sapiens
aspartic intramembrane protease
-
 Rattus norvegicus
signal peptide peptidase-like 2a
-
 Mus musculus
signal peptide peptidase-like 2a
-
 Homo sapiens
signal peptide peptidase-like 2a
-
 Rattus norvegicus
SPPL2a
-
 Mus musculus
SPPL2a
-
 Homo sapiens
SPPL2a
-
 Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000005
-
 pH 7.4, 37°C, liver microsomes Homo sapiens (2R)-N4-(3,5-difluorophenyl)-2-methyl-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
0.000035
-
 pH 7.4, 37°C, liver microsomes Homo sapiens (2R)-2-methyl-N4-(2-methylphenyl)-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
0.000044
-
 pH 7.4, 37°C, liver microsomes Homo sapiens (2R)-N4-(5-fluoro-2-methylpyridin-3-yl)-2-methyl-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
0.00007
-
 pH 7.4, 37°C, liver microsomes Homo sapiens (2R)-2-methyl-N4-(3-methylphenyl)-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
0.000076
-
 pH 7.4, 37°C, liver microsomes Homo sapiens (2R)-N4-(5-fluoro-2-methylpyridin-3-yl)-N1-[(10S)-6-fluoro-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]-2-methylbutanediamide
0.000077
-
 pH 7.4, 37°C, liver microsomes Homo sapiens (2S)-2-cyclopropyl-N1-[(10'S)-5',11'-dioxo-10',11'-dihydro-5'H-spiro[cyclopropane-1,2'-pyrazolo[1,2-b][2,3]benzodiazepin]-10'-yl]-N4-(5-fluoro-2-methylpyridin-3-yl)butanediamide
0.000225
-
 pH 7.4, 37°C, liver microsomes Homo sapiens (2S)-2-cyclopropyl-N1-[(10S)-5,11-dioxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]-N4-(5-fluoro-2-methylpyridin-3-yl)butanediamide
0.00087
-
 pH 7.4, 37°C, liver microsomes Homo sapiens (2R)-N1-[(10S)-5,11-dioxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]-N4-(5-fluoro-2-methylpyridin-3-yl)-2-methylbutanediamide
0.00102
-
 pH 7.4, 37°C, liver microsomes Homo sapiens (2R)-2-methyl-N4-(2-methylpyridin-3-yl)-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
0.00139
-
 pH 7.4, 37°C, liver microsomes Homo sapiens (2R)-2-methyl-N4-(4-methylphenyl)-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]butanediamide
0.00285
-
 pH 7.4, 37°C, liver microsomes Homo sapiens (2R)-2-methyl-N1-[(10S)-11-oxo-2,3,10,11-tetrahydro-1H,5H-pyrazolo[1,2-b][2,3]benzodiazepin-10-yl]-N4-[2-(trifluoromethyl)phenyl]butanediamide
0.006
-
 pH 7.4, 37°C Homo sapiens 2,2'-(2-oxo-1,3-propanediyl)bis[N-[(phenylmethoxy)carbonyl]-L-leucyl-L-leucinamide]
0.01
-
 pH 7.4, 37°C Homo sapiens LY-411,575

General Information

General Information Comment Organism
physiological function signal peptide peptidase-like 2a (SPPL2a) is an aspartic intramembrane protease playing an important role in the development and function of antigen presenting cells such as B-lymphocytes and dendritic cells Mus musculus
physiological function signal peptide peptidase-like 2a (SPPL2a) is an aspartic intramembrane protease playing an important role in the development and function of antigen presenting cells such as B-lymphocytes and dendritic cells Homo sapiens
physiological function signal peptide peptidase-like 2a (SPPL2a) is an aspartic intramembrane protease playing an important role in the development and function of antigen presenting cells such as B-lymphocytes and dendritic cells Rattus norvegicus