Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary 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

Application

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

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.3.1.22 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

EC Number Inhibitors Comment Organism Structure
1.3.1.22 (+/-)-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
1.3.1.22 (10bR)-8-chloro-4,10b-dimethyl-4a,5,6,10b-tetrahydrophenanthridin-2(1H)-one isoform II, 49% inhibition at 0.02 mM Homo sapiens
1.3.1.22 (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
1.3.1.22 (10bR)-8-chloro-5,10b-dimethyl-4a,5,6,10b-tetrahydrophenanthridin-2(1H)-one isoform II, 42% inhibition at 0.03 mM Homo sapiens
1.3.1.22 (4aS)-7-chloro-4a-methyl-2,3,4,4a-tetrahydrophenanthrene-2-carboxylic acid
-
 Homo sapiens
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 (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
1.3.1.22 1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 298 nM Homo sapiens
1.3.1.22 10-azasteroids several Homo sapiens
1.3.1.22 2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid
-
 Homo sapiens
1.3.1.22 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
1.3.1.22 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
1.3.1.22 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
1.3.1.22 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
1.3.1.22 4-azasteroids
-
 Homo sapiens
1.3.1.22 4-methyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 185 nM Homo sapiens
1.3.1.22 4-methyl-5,6-dihydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 1400 nM Homo sapiens
1.3.1.22 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
1.3.1.22 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
1.3.1.22 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
1.3.1.22 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
1.3.1.22 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
1.3.1.22 6-azasteroids several Homo sapiens
1.3.1.22 7-bromo-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid
-
 Homo sapiens
1.3.1.22 7-chloro-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid
-
 Homo sapiens
1.3.1.22 8-bromo-4-methyl-1,4,5,6-tetrahydrobenzo[f]quinolin-3(2H)-one 50% inhibition at 60 nM, isoform I Homo sapiens
1.3.1.22 8-chloro-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 49 nM Homo sapiens
1.3.1.22 8-chloro-1,4,5,6-tetrahydrobenzo[f]quinolin-3(2H)-one 50% inhibition at 460 nM, isoform I Homo sapiens
1.3.1.22 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
1.3.1.22 8-chloro-4,4a,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 459 nM Homo sapiens
1.3.1.22 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
1.3.1.22 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
1.3.1.22 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
1.3.1.22 8-chloro-4-methyl-1,4,5,6-tetrahydrobenzo[f]quinolin-3(2H)-one 50% inhibition at 30 nM, isoform I Homo sapiens
1.3.1.22 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
1.3.1.22 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
1.3.1.22 8-fluoro-1,4,5,6-tetrahydrobenzo[f]quinolin-3(2H)-one 50% inhibition at 600 nM, isoform I Homo sapiens
1.3.1.22 8-methyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 376 nM Homo sapiens
1.3.1.22 8-methyl-4,4a,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I, 50% inhibition at 176 nM Homo sapiens
1.3.1.22 benzoquilizin-3-ones diverse, mimics of 10-azasteroids, overview, structure-activity relationships Homo sapiens
1.3.1.22 benzoquinolines compounds as mimics of 4-azasteroid inhibitors, diverse, overview, compounds derived from 6-azasteroids, overview Homo sapiens
1.3.1.22 dutasteride inhibits both isozymes, used in treatment of benign protstate hyperplasia, reduction of serum dihydrotestosterone levels Homo sapiens
1.3.1.22 epristeride
-
 Homo sapiens
1.3.1.22 finasteride 4-azasteroid, specific for isozyme 5alphaR-2, used in treatment of benign protstate hyperplasia, reduction of serum dihydrotestosterone levels Homo sapiens
1.3.1.22 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
1.3.1.22 MK386 steroidal inhibitor Homo sapiens
1.3.1.22 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
1.3.1.22 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
1.3.1.22 non-steroidal bi-substrate inhibitors several, structures, overview Homo sapiens
1.3.1.22 ONO 3805
-
 Homo sapiens
1.3.1.22 ONO-3805 a non-steroidal bi-substrate inhibitor Homo sapiens
1.3.1.22 steroid carboxylic acid compounds diverse, tricyclic aryl acid mimics of, overview Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.3.1.22 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

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

Reaction

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

Source Tissue

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

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.3.1.22 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 ?
1.3.1.22 testosterone + NADPH + H+ reaction mechanism Homo sapiens 5alpha-dihydrotestosterone + NADP+
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.3.1.22 5alphaR
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.3.1.22 NADPH
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.3.1.22 additional information
-
 additional information isozyme-specific IC50-values of diverse inhibitors, overview Homo sapiens
1.3.1.22 0.0000027
-
 8-chloro-4-methyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I Homo sapiens
1.3.1.22 0.000004
-
 (-)-LY191704
-
 Homo sapiens
1.3.1.22 0.000005
-
 finasteride isozyme 5alphaR-2 Homo sapiens
1.3.1.22 0.0000058
-
 4,8-dimethyl-1,2,5,6-tetrahydro-3H-pyrido[1,2-a]quinolin-3-one isoform I Homo sapiens
1.3.1.22 0.000006
-
 (+)-LY191704
-
 Homo sapiens
1.3.1.22 0.000026
-
 7-bromo-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform I, Ki,app-value Homo sapiens
1.3.1.22 0.00026
-
 (4aS)-7-chloro-4a-methyl-2,3,4,4a-tetrahydrophenanthrene-2-carboxylic acid isoform II, Ki,app-value Homo sapiens
1.3.1.22 0.0003
-
 finasteride isozyme 5alphaR-1 Homo sapiens
1.3.1.22 0.000315
-
 2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform I, Ki,app-value Homo sapiens
1.3.1.22 0.00032
-
 7-chloro-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform I, Ki,app-value Homo sapiens
1.3.1.22 0.00092
-
 (10bR)-8-chloro-4,10b-dimethyl-4a,5,6,10b-tetrahydrophenanthridin-2(1H)-one isoform I Homo sapiens
1.3.1.22 0.0011
-
 (10bR)-8-chloro-4,5,10b-trimethyl-4a,5,6,10b-tetrahydrophenanthridin-2(1H)-one isoform I Homo sapiens
1.3.1.22 0.0012
-
 (4aS)-7-chloro-4a-methyl-2,3,4,4a-tetrahydrophenanthrene-2-carboxylic acid isoform I, Ki,app-value Homo sapiens
1.3.1.22 0.0025
-
 7-chloro-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform II, Ki,app-value Homo sapiens
1.3.1.22 0.01
-
 2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform II, Ki,app-value Homo sapiens
1.3.1.22 0.01
-
 7-bromo-2,4a,9,10-tetrahydrophenanthrene-2-carboxylic acid isoform II, Ki,app-value Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.3.1.22 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