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Literature summary for 1.3.1.22 extracted from

  • Occhiato, E.G.; Guarna, A.; Danza, G.; Serio, M.
    Selective non-steroidal inhibitors of 5alpha-reductase type 1 (2004), J. Steroid Biochem. Mol. Biol., 88, 1-16.
    View publication on PubMed
Search for more literature for 1.3.1.22

Application

Application Comment Organism
pharmacology enzyme is a target for drug developement Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of isozymes 5alphaR-1 and 5alphaR-2 in e.g. human DU145 cells, in COS-1 cells, and in CHO 1827 and CHO 1829 cells, isozymes are chromosomal differently localized Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(+/-)-LY191704 i.e. (4aS,10aR)-7-chloro-1-methyl-3,4,4a,9,10,10a-hexahydrophenanthren-2(1H)-one, non-steroidal, most potent benzoquinoline mimicing 4-azasteroid inhibitors, and specific for isozyme 5alphaR-1, IC50 is 30 nM Homo sapiens
(10bR)-8-chloro-4,10b-dimethyl-4a,5,6,10b-tetrahydrophenanthridin-2(1H)-one isoform II, 49% inhibition at 0.02 mM Homo sapiens
(10bR)-8-chloro-4,5,10b-trimethyl-4a,5,6,10b-tetrahydrophenanthridin-2(1H)-one isoform II, 57% inhibition at 0.029 mM Homo sapiens
(10bR)-8-chloro-5,10b-dimethyl-4a,5,6,10b-tetrahydrophenanthridin-2(1H)-one isoform II, 42% inhibition at 0.03 mM Homo sapiens
(4aS)-7-chloro-4a-methyl-2,3,4,4a-tetrahydrophenanthrene-2-carboxylic acid
-
 Homo sapiens
(4aS,10bS)-4,10b-dimethyl-8-[(E)-2-naphthylylvinyl]-1,4,4a,5,6,10b-hexahydrobenzo[f]quinolin-3(2H)-one isoform I, 50% inhibition at 6 nM, isoform II, 50% inhibition at 0.00134 mM Homo sapiens
(4aS,10bS)-4,10b-dimethyl-8-[(E)-2-phenylvinyl]-1,4,4a,5,6,10b-hexahydrobenzo[f]quinolin-3(2H)-one isoform I, 50% inhibition at 6 nM, isoform II, 50% inhibition at 0.0014 mM Homo sapiens
(4aS,10bS)-4,8-dimethyl-1,4,4a,5,6,10b-hexahydrobenzo[f]quinolin-3(2H)-one isoform I, 50% inhibition at 11 nM Homo sapiens
(4aS,10bS)-8-(2-furyl)-4,10b-dimethyl-1,4,4a,5,6,10b-hexahydrobenzo[f]quinolin-3(2H)-one isoform I, 50% inhibition at 59 nM, isoform II, 50% inhibition above 10 nM Homo sapiens
(4aS,10bS)-8-bromo-4-methyl-1,4,4a,5,6,10b-hexahydrobenzo[f]quinolin-3(2H)-one isoform I, 50% inhibition at 35 nM Homo sapiens
(4aS,10bS)-8-chloro-1,4,4a,5,6,10b-hexahydrobenzo[f]quinolin-3(2H)-one isoform I, 50% inhibition at 60 nM Homo sapiens
(4aS,10bS)-8-chloro-4,10b-dimethyl-1,4,4a,5,6,10b-hexahydrobenzo[f]quinolin-3(2H)-one isoform I, 50% inhibition at 17 nM Homo sapiens
(4aS,10bS)-8-chloro-4-methyl-1,4,4a,5,6,10b-hexahydrobenzo[f]quinolin-3(2H)-one isoform I, 50% inhibition at 8 nM, isoform II, 50% inhibition above 0.01 mM Homo sapiens
(4aS,10bS)-8-fluoro-4-methyl-1,4,4a,5,6,10b-hexahydrobenzo[f]quinolin-3(2H)-one isoform I, 50% inhibition at 35 nM Homo sapiens
(4aS,10bS)-8-methoxy-4-methyl-1,4,4a,5,6,10b-hexahydrobenzo[f]quinolin-3(2H)-one isoform I, 50% inhibition at 120 nM Homo sapiens
(4R)-4,8-dimethyl-4,4a,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 312 nM Homo sapiens
(4R)-8-chloro-4-methyl-4,4a,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 141 nM Homo sapiens
(4S)-4,8-dimethyl-4,4a,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 137 nM Homo sapiens
(6R)-8-chloro-6-methyl-4,4a,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 188 nM Homo sapiens
1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 298 nM Homo sapiens
10-azasteroids several Homo sapiens
2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid
-
 Homo sapiens
4,6,8-trimethyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 15.8 nM Homo sapiens
4,8-dimethyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 20 nM Homo sapiens
4-(2-[5-[(diphenylmethyl)carbamoyl]-1-benzofuran-2-yl]phenoxy)butanoic acid isoform I, 50% inhibition at 310 nM, isoform II, 50% inhibition above 0.1 mM Homo sapiens
4-(2-[6-[(diphenylmethyl)carbamoyl]-1-benzofuran-2-yl]phenoxy)butanoic acid isoform I, 50% inhibition at 62 nM, isoform II, 50% inhibition at 270 nM Homo sapiens
4-azasteroids
-
 Homo sapiens
4-methyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 185 nM Homo sapiens
4-methyl-5,6-dihydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 1400 nM Homo sapiens
4-[2-(6-[[bis(4-fluorophenyl)methyl]carbamoyl]-1-benzofuran-2-yl)phenoxy]butanoic acid isoform I, 50% inhibition at 50 nM, isoform II, 50% inhibition at 340 nM Homo sapiens
4-[2-(6-[[bis(4-methoxyphenyl)methyl]amino]-1-benzofuran-2-yl)phenoxy]butanoic acid isoform I, 50% inhibition at 42 nM, isoform II, 50% inhibition at 480 nM Homo sapiens
4-[2-(6-[[bis(4-methoxyphenyl)methyl]carbamoyl]-1-benzofuran-2-yl)phenoxy]butanoic acid isoform I, 50% inhibition at 130 nM, isoform II, 50% inhibition at 930 nM Homo sapiens
4-[3-[(2,2-diphenyl-1,3-benzodioxol-5-yl)oxy]-2-methyl-1H-indol-1-yl]butanoic acid isoform I, 50% inhibition at 10 nM, isoform II, 50% inhibition at 6300 nM Homo sapiens
6,8-dimethyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 14.3 nM Homo sapiens
6-azasteroids several Homo sapiens
7-bromo-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid
-
 Homo sapiens
7-chloro-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid
-
 Homo sapiens
8-bromo-4-methyl-1,4,5,6-tetrahydrobenzo[f]quinolin-3(2H)-one 50% inhibition at 60 nM, isoform I Homo sapiens
8-chloro-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 49 nM Homo sapiens
8-chloro-1,4,5,6-tetrahydrobenzo[f]quinolin-3(2H)-one 50% inhibition at 460 nM, isoform I Homo sapiens
8-chloro-1-methyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 204 nM Homo sapiens
8-chloro-4,4a,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 459 nM Homo sapiens
8-chloro-4,5-dimethyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 15.6 nM Homo sapiens
8-chloro-4,6-dimethyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 8.5 nM Homo sapiens
8-chloro-4-methyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 7.6 nM Homo sapiens
8-chloro-4-methyl-1,4,5,6-tetrahydrobenzo[f]quinolin-3(2H)-one 50% inhibition at 30 nM, isoform I Homo sapiens
8-chloro-5-methyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 346 nM Homo sapiens
8-chloro-6-methyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 14.4 nM Homo sapiens
8-fluoro-1,4,5,6-tetrahydrobenzo[f]quinolin-3(2H)-one 50% inhibition at 600 nM, isoform I Homo sapiens
8-methyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 376 nM Homo sapiens
8-methyl-4,4a,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 176 nM Homo sapiens
benzoquilizin-3-ones diverse, mimics of 10-azasteroids, overview, structure-activity relationships Homo sapiens
benzoquinolines compounds as mimics of 4-azasteroid inhibitors, diverse, overview, compounds derived from 6-azasteroids, overview Homo sapiens
dutasteride inhibits both isozymes, used in treatment of benign protstate hyperplasia, reduction of serum dihydrotestosterone levels Homo sapiens
epristeride
-
 Homo sapiens
finasteride 4-azasteroid, specific for isozyme 5alphaR-2, used in treatment of benign protstate hyperplasia, reduction of serum dihydrotestosterone levels Homo sapiens
FK143 i.e. 4-[3-(3-[[bis-(4-isobutyl-phenyl)-methyl]amino]-benzoyl)-indol-1-yl]-butyric acid, a non-steroidal bi-substrate inhibitor Homo sapiens
MK386 steroidal inhibitor Homo sapiens
additional information kinetic inhibition mechanism of steroidal and non-steroidal inhibitors, competitive steroidal inhibitors, type A or type B, act with a substrate-like or a product-like transition state, type C uncompetitive steroidal inhibitors, overview Homo sapiens
N,N-bis(1-methylethyl)-4-(1-methyl-2-oxo-1,2-dihydroquinolin-6-yl)benzamide isoform I, 50% inhibition at 510 nM, isoform II, 9% inhibition at 0.01 mM Homo sapiens
non-steroidal bi-substrate inhibitors several, structures, overview Homo sapiens
ONO 3805
-
 Homo sapiens
ONO-3805 a non-steroidal bi-substrate inhibitor Homo sapiens
steroid carboxylic acid compounds diverse, tricyclic aryl acid mimics of, overview Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
testosterone + NADPH + H+ Homo sapiens
-
 5alpha-dihydrotestosterone + NADP+ 5alpha-dihydrotestosterone is a potent androgen, abnormal overproduction is associated with pathologies of mainly prostate and skin, e.g. benign prostatic hyperplasia, prostate cancer, acne, androgenetic alopecia in men, and hirsutism in women, with different involvement of the isozymes ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Homo sapiens
-
 male and female, 2 isozymes 5alphaR-1 and 5alphaR-2
-

Reaction

Reaction Comment Organism Reaction ID
a 3-oxo-5alpha-steroid + NADP+ = a 3-oxo-DELTA4-steroid + NADPH + H+ reaction mechanism Homo sapiens
a

Source Tissue

Source Tissue Comment Organism Textmining
fibroblast foreskin, Hs68 Homo sapiens
-
HS-68 cell
-
 Homo sapiens
-
additional information isozymes show different tissue distribution in androgen target organs Homo sapiens
-
prostate isozymes 5alphaR-1 and 5alphaR-2, only isozyme 5alphaR-1 is found in case of prostate cancer Homo sapiens
-
skin isozymes 5alphaR-1 and 5alphaR-2, dihydrotestosterone overproduction in skin pathologies, overview Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
testosterone + NADPH + H+
-
 Homo sapiens 5alpha-dihydrotestosterone + NADP+ 5alpha-dihydrotestosterone is a potent androgen, abnormal overproduction is associated with pathologies of mainly prostate and skin, e.g. benign prostatic hyperplasia, prostate cancer, acne, androgenetic alopecia in men, and hirsutism in women, with different involvement of the isozymes ?
testosterone + NADPH + H+ reaction mechanism Homo sapiens 5alpha-dihydrotestosterone + NADP+
-
 ?

Synonyms

Synonyms Comment Organism
5alphaR
-
 Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADPH
-
 Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
 additional information isozyme-specific IC50-values of diverse inhibitors, overview Homo sapiens
0.0000027
-
 8-chloro-4-methyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I Homo sapiens
0.000004
-
 (-)-LY191704
-
 Homo sapiens
0.000005
-
 finasteride isozyme 5alphaR-2 Homo sapiens
0.0000058
-
 4,8-dimethyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I Homo sapiens
0.000006
-
 (+)-LY191704
-
 Homo sapiens
0.000026
-
 7-bromo-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform I, Ki,app-value Homo sapiens
0.00026
-
 (4aS)-7-chloro-4a-methyl-2,3,4,4a-tetrahydrophenanthrene-2-carboxylic acid isoform II, Ki,app-value Homo sapiens
0.0003
-
 finasteride isozyme 5alphaR-1 Homo sapiens
0.000315
-
 2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform I, Ki,app-value Homo sapiens
0.00032
-
 7-chloro-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform I, Ki,app-value Homo sapiens
0.00092
-
 (10bR)-8-chloro-4,10b-dimethyl-4a,5,6,10b-tetrahydrophenanthridin-2(1H)-one isoform I Homo sapiens
0.0011
-
 (10bR)-8-chloro-4,5,10b-trimethyl-4a,5,6,10b-tetrahydrophenanthridin-2(1H)-one isoform I Homo sapiens
0.0012
-
 (4aS)-7-chloro-4a-methyl-2,3,4,4a-tetrahydrophenanthrene-2-carboxylic acid isoform I, Ki,app-value Homo sapiens
0.0025
-
 7-chloro-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform II, Ki,app-value Homo sapiens
0.01
-
 2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform II, Ki,app-value Homo sapiens
0.01
-
 7-bromo-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform II, Ki,app-value Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00003
-
 i.e. (4aS,10aR)-7-chloro-1-methyl-3,4,4a,9,10,10a-hexahydrophenanthren-2(1H)-one, non-steroidal, most potent benzoquinoline mimicing 4-azasteroid inhibitors, and specific for isozyme 5alphaR-1, IC50 is 30 nM Homo sapiens (+/-)-LY191704