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(2E)-3-(3,3-dimethyl-3,4-dihydro-2H-1-benzopyran-6-yl)prop-2-enoate
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(2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
93.3% inhibition at 0.1 mM
(2E)-3-(4-ethylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
89.1% inhibition at 0.1 mM
(2E)-3-(4-methylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
92.7% inhibition at 0.1 mM
(2E)-3-prop-2-enoic acid
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(2E)-3-[3-(3-methylbut-2-en-1-yl)-4-[(3-phenylpropanoyl)oxy]phenyl]prop-2-enoate
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(2E)-3-[3-(3-methylbut-2-en-1-yl)-4-[(3-phenylpropanoyl)oxy]phenyl]prop-2-enoic acid
i.e. baccharin, a component of Brazilian propolis, exhibits a high inhibitory potency and selectivity for AKR1C3 over other AKR1C isoforms. When the cinnamic acid group of baccharin is esterified, there is a dramatic decrease in potency and selectivity for AKR1C3 in comparison to baccharin. Low or submicromolar inhibition is observed when the 3-prenyl group of baccharin is removed, and the selectivity over AKR1C2 is low. Inhibition of NAD+ dependent oxidation of S-tetralol
(2E)-3-[4-(acetyloxy)-3-(3-methylbut-2-en-1-yl)phenyl]prop-2-enoate
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(2E)-3-[4-(acetyloxy)-3-(3-methylbut-2-en-1-yl)phenyl]prop-2-enoic acid
-
(2E)-3-[4-(benzoyloxy)phenyl]prop-2-enoic acid
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(2E)-3-[4-(methylsulfanyl)phenyl]-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
93.5% inhibition at 0.1 mM
(2E)-3-[4-(pyridine-4-carbonyloxy)phenyl]prop-2-enoic acid
-
(2E)-3-[4-hydroxy-3-(3-methylbut-2-en-1-yl)phenyl]prop-2-enoate
37% inhibition at 0.010 mM
(4-chlorophenyl)(5-methoxy-2-methyl-1H-indol-1-yl)methanone
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(E)-3-(3-((3-phenylpropanoyl)oxy)phenyl)acrylic acid
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(Z/E)-3-(4-((3-phenylpropanoyl)oxy)phenyl)acrylic acid
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(Z/E)-tert-butyl 3-(4-(3-phenylpropanoyloxy)phenyl)acrylate
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1-(4-[[(2R)-2-methylpiperidin-1-yl]sulfonyl]phenyl)-1,3-dihydro-2H-pyrrol-2-one
IC50 value in HCT-116 cells engineered to over-express AKR1C3 is 11 nM
1-(4-[[(2R,6S)-2,6-dimethylpiperidin-1-yl]sulfonyl]phenyl)pyrrolidin-2-one
IC50 value in HCT-116 cells engineered to over-express AKR1C3 is 22 nM
1-[4-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)phenyl]pyrrolidin-2-one
IC50 value in HCT-116 cells engineered to over-express AKR1C3 is 24 nM
17alpha-methyltestosterone
-
competitive inhibition
17beta-estradiol
-
0.175 mM, 25-40% inhibition of testosterone oxidation
2'-des-methyl-indomethacin
the cofactor binding cavity of AKR1C3 is not perturbed upon binding of the inhibitor
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2-(2,4-dioxo-1,3-thiazolidin-5-yl)-N-(2-hydroxyphenyl)acetamide
inhibitor is about 1000times more selective for isoform AKR1C3 over AKR1C2, and selectivity is even higher when compared with AKR1C1 and AKR1C4
2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-(2-methylbenzene-1-sulfonyl)acetamide
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2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-(4-cyanobenzene-1-sulfonyl)acetamide
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2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-(4-fluorobenzene-1-sulfonyl)acetamide
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2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-(4-methoxybenzene-1-sulfonyl)acetamide
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2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-(4-methylbenzene-1-sulfonyl)acetamide
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2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-(4-phenoxybenzene-1-sulfonyl)acetamide
-
2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-(5-chlorothiophene-2-sulfonyl)acetamide
-
2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-(methanesulfonyl)acetamide
-
2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-(naphthalene-2-sulfonyl)acetamide
-
2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-(trifluoromethanesulfonyl)acetamide
-
2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-[3-(trifluoromethyl)benzene-1-sulfonyl]acetamide
-
2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-[4-(propan-2-yl)benzene-1-sulfonyl]acetamide
-
2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]-N-[4-(trifluoromethyl)benzene-1-sulfonyl]acetamide
-
2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-(trifluoromethanesulfonyl)acetamide
-
2-[[(3-hydroxyphenyl)carbonyl]amino]-4,5-dimethoxybenzoic acid
-
2-[[(3-hydroxyphenyl)carbonyl]amino]-5-nitrobenzoic acid
-
21-hydroxypregn-4-ene-3,20-dione
-
0.010 mM, 73% inhibition
3-((4-nitronaphthalen-1-yl)amino)benzoic acid
inhibitor nanomolar potency and selective inhibition of isoform AKR1C3 but also acts as an androgen receptor antagonist. It inhibits 5alpha-dihydrotestosterone stimulated androgen receptor reporter gene activity with an IC50 value of 4.7 microM and produces a concentration dependent reduction in androgen receptor levels in prostate cancer cells
3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoate
-
3-(5-methoxy-2-methyl-1H-indol-3-yl)propanoic acid
-
3-(phenylamino)benzoic acid
-
3-phenoxybenzoic acid
inhibitor carboxylic acid binds to the oxyanion site, in which the carboxylate group very closely overlays the acetate molecule found in other AKR1C3 structures and forms hydrogen bonds to the enzyme catalytic residues His117 and Tyr55, as well as to a conserved water network located in and near the SP3 subpocket. The 3-phenoxy ring extends into the SP1 subpocket and makes van der Waals contacts with the aromatic residues Phe306, Phe311 and Tyr319 that line the pocket
3-[(4-nitrophenyl)amino]benzoic acid
94fold selectivity for the inhibition of isoform AKR1C3 over AKR1C2
3-[1-(4-chlorobenzoyl)-2-ethyl-5-methoxy-1H-indol-3-yl]propanoic acid
-
3-[1-(4-chlorobenzoyl)-3-ethyl-5-methoxy-1H-indol-2-yl]propanoic acid
-
3-[1-(4-chlorobenzoyl)-5-fluoro-2-methyl-1H-indol-3-yl]propanoic acid
-
3-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]propanoic acid
-
3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-2,2-dimethylpropanoic acid
-
3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-2-methylpropanoic acid
-
3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-N-(2-methylbenzene-1-sulfonyl)propanamide
-
3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-N-(4-methylbenzene-1-sulfonyl)propanamide
-
3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-N-(5-chlorothiophene-2-sulfonyl)propanamide
-
3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-N-(methanesulfonyl)-2-methylpropanamide
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3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-N-(methanesulfonyl)propanamide
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3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-N-(naphthalene-2-sulfonyl)propanamide
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3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-N-(trifluoromethanesulfonyl)propanamide
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3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-N-[4-(propan-2-yl)benzene-1-sulfonyl]propanamide
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3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-N-[4-(trifluoromethoxy)benzene-1-sulfonyl]propanamide
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3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]-N-[4-(trifluoromethyl)benzene-1-sulfonyl]propanamide
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3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]propanoic acid
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3-[[4-(methoxymethyl)phenyl]amino]benzoic acid
360fold selectivity for the inhibition of isoform AKR1C3 over AKR1C2
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
3a-phenyl-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one
inhibitor shows 17fold and 30fold selectivity against isoforms AKR1C2 and AKR1C1, respectively, and much higher selectivity against AKR1C4
3beta-cyclohexylethyl-androsterone
-
potent inhibitor
3beta-n-hexyl-androsterone
-
potent inhibitor
3beta-phenylethyl-androsterone
-
potent inhibitor
4-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]butanoic acid
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5-bromo-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
5-chloro-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
5-methoxy-3-(2-oxobutyl)-1H-indole-1-carboxylic acid
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5alpha-Androstan-3beta-ol-17-one
-
0.005 mM, 55% inhibition
5alpha-pregnan-3beta-ol-20-one
-
0.005 mM, 52% inhibition
5beta-androstan-3,17-dione
-
product inhibition, forward reaction
5beta-androstan-3beta-ol-17-one
-
0.005 mM, 87% inhibition
5beta-dihydrotestosterone
-
product inhibition, reverse reaction
5beta-Pregnan-3beta-ol-20-one
-
0.005 mM, 81% inhibition
6-methoxy-9-[3-(trifluoromethyl)benzoyl]-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid
-
7-hydroxyflavone
-
0.007 mM, 50% inhibition, oxidation of androstandiol
9-(4-chlorobenzoyl)-6-methoxy-2,3,4,9-tetrahydro-1H-carbazole-2-carboxylic acid
-
9-(4-chlorobenzoyl)-6-methoxy-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid
-
9-(4-chlorobenzoyl)-N-(methanesulfonyl)-6-methoxy-2,3,4,9-tetrahydro-1H-carbazole-3-carboxamide
-
abietic acid
-
0.010 mM, 50% inhibition, oxidation of androstandiol
Ag+
-
0.1 mM, complete inhibition
biochain A
-
0.014 mM, 50% inhibition, reduction of androst-4-ene-3,17-dione, 0.008 mM, oxidation of androstanediol
chrysin
-
0.010 mM, 50% inhibition, oxidation of androstandiol
coumestrol
-
0.005 mM, 50% inhibition, reduction of androst-4-ene-3,17-dione, 0.011 mM, 50% inhibition, oxidation of androstanediol
CuCl2
-
1 mM, complete inhibition
dexamethasone
-
0.10 mM, 39% inhibition
Dienstrol
-
0.010 mM, 60% inhibition
FeCl3
-
10 mM, 46% inhibition
Hg2+
-
0.1 mM, complete inhibition
ikarisoside A
competitive; competitive
Medroxyprogesterone acetate
-
0.010 mM, 22% inhibition
methyl 5-methoxy-3-(2-oxobutyl)-1H-indole-1-carboxylate
-
methyl [1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]acetate
-
methyl [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetate
-
methyl [5-methoxy-1-(4-methoxybenzoyl)-2-methyl-1H-indol-3-yl]acetate
-
methyl [5-methoxy-2-methyl-1-(4-methylbenzoyl)-1H-indol-3-yl]acetate
-
N-(4-acetylbenzene-1-sulfonyl)-2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]acetamide
-
N-(4-acetylbenzene-1-sulfonyl)-3-[1-(4-chlorobenzoyl)-5-methoxy-3-methyl-1H-indol-2-yl]propanamide
-
N-(4-bromobenzene-1-sulfonyl)-2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]acetamide
-
N-(4-chlorobenzoyl)-melatonin
-
N-benzoylanthranilic acid
-
N-[2,5-bis(trifluoromethyl)benzene-1-sulfonyl]-2-[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]acetamide
-
NaCN
-
1 mM, 50% inhibition
naringenin
-
0.010 mM, 50% inhibition, oxidation of androstandiol
p-chloromercuribenzoate
-
0.1 mM, complete inhibition
Sodium amytal
-
10 mM, 25% inhibition
stilboestrol
-
0.010 mM, 61% inhibition
tert-butyl(2E)-3-[3-(3-methylbut-2-en-1-yl)-4-[(3-phenylpropanoyl)oxy]phenyl]prop-2-enoate
-
Triton X-100
-
immediate loss of 60-70% activity, remaining activity is stable for 4 days, competitive vs. testosterone, non-competitive vs. NAD+
ZnCl2
-
10 mM, 10% inhibition
[1-(4-chlorobenzoyl)-5-fluoro-1H-indol-3-yl]acetic acid
-
[1-(4-chlorobenzoyl)-5-fluoro-2-methyl-1H-indol-3-yl]acetic acid
-
[1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl]acetic acid
-
[1-(4-chlorobenzoyl)-5-methoxy-2-propyl-1H-indol-3-yl]acetic acid
-
[1-(4-fluorobenzoyl)-5-methoxy-1H-indol-3-yl]acetic acid
-
[1-(4-fluorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid
-
[1-[4-(chloromethyl)benzoyl]-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid
-
[5-fluoro-2-methyl-1-[3-(trifluoromethyl)benzoyl]-1H-indol-3-yl]acetic acid
-
[5-methoxy-1-(4-methoxybenzoyl)-2-methyl-1H-indol-3-yl]acetic acid
-
[5-methoxy-1-[3-(trifluoromethyl)benzoyl]-1H-indol-3-yl]acetic acid
-
[5-methoxy-1-[4-(trifluoromethyl)benzoyl]-1H-indol-3-yl]acetic acid
-
[5-methoxy-2-methyl-1-(4-methylbenzoyl)-1H-indol-3-yl]acetic acid
-
[5-methoxy-2-methyl-1-[3-(trifluoromethyl)benzoyl]-1H-indol-3-yl]acetic acid
-
[5-methoxy-2-methyl-1-[4-(trifluoromethyl)benzoyl]-1H-indol-3-yl]acetic acid
-
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
250fold selectivity for the inhibition of isoform AKR1C3 over AKR1C2
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
in complex with AKR1C3. Compound adopts a similar binding orientation as flufenamic acid, however, its phenylamino ring projects deeper into a subpocket and confers selectivity over the other AKR1C isoforms
Hexestrol
-
Hexestrol
competitive; competitive
Hexoestrol
-
0.010 mM, 62% inhibition
hinokitiol
-
hinokitiol
competitive; competitive
indomethacin
-
indomethacin
-
0.10 mM, 67% inhibition
kaempferol
-
0.008 mM, 50% inhibition, oxidation of androstandiol
Phenolphthalein
-
quercetin
-
0.009 mM, 50% inhibition, reduction of androst-4-ene-3,17-dione, 0.005 mM, oxidation of androstanediol
zearalenone
-
0.004 mM, 50% inhibition, reduction of androst-4-ene-3,17-dione, 0.002 mM, oxidation of androstanediol
zearalenone
competitive; competitive
additional information
development of potent and selective indomethacin analogues for the inhibition of AKR1C3 in castrate-resistant prostate cancer, overview. Increasing the length of the aliphatic side chain of indomethacin from -ethyl to -propyl leads to a 2fold reduction in AKR1C3 potency, but the compound retained 257fold selectivity for AKR1C3 over AKR1C2
-
additional information
screening of baccharin analogues as selective inhibitors against type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3), selectivity versus AKR1C2
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additional information
no or poor inhibition by 7-hydroxyflavone, chrysin, quercetin, genistein, galangin, lithocholic acid, and zearalenone
-