Target Information

Target General Information

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Target ID

T27265 (Former ID: TTDS00240)

Target Name

Oxo-5-alpha-steroid 4-dehydrogenase (SRD5A)

Synonyms

Steroid 5-alpha-reductase; SR; S5AR; 3-oxo-5-alpha-steroid 4-dehydrogenase

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Gene Name

SRD5A1; SRD5A2; SRD5A3

Target Type

Successful target

[1]

Disease

[+] 3 Target-related Diseases

Acne vulgaris [ICD-11: ED80]

Prostate cancer [ICD-11: 2C82]

Prostate hyperplasia [ICD-11: GA90]

Function

Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.

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BioChemical Class

CH-CH donor oxidoreductase

UniProt ID

S5A1_HUMAN ; S5A2_HUMAN ; PORED_HUMAN

Sequence

MATATGVAEERLLAALAYLQCAVGCAVFARNRQTNSVYGRHALPSHRLRVPARAAWVVQE
LPSLALPLYQYASESAPRLRSAPNCILLAMFLVHYGHRCLIYPFLMRGGKPMPLLACTMA
IMFCTCNGYLQSRYLSHCAVYADDWVTDPRFLIGFGLWLTGMLINIHSDHILRNLRKPGD
TGYKIPRGGLFEYVTAANYFGEIMEWCGYALASWSVQGAAFAFFTFCFLSGRAKEHHEWY
LRKFEEYPKFRKIIIPFLF

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Drugs and Modes of Action

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Approved Drug(s)

[+] 4 Approved Drugs

Azelaic Acid

Drug Info

Approved

Acne vulgaris

[2], [3], [4]

Dutasteride

Drug Info

Approved

Benign prostatic hyperplasia

[5], [6]

Finasteride

Drug Info

Approved

Benign prostatic hyperplasia

[7], [8]

Polyestradiol Phosphate

Drug Info

Approved

Prostate cancer

[4]

Clinical Trial Drug(s)

[+] 5 Clinical Trial Drugs

Dutasteride + tamsulosin

Drug Info

Phase 3

Benign prostatic hyperplasia

[9]

Epristeride

Drug Info

Phase 3

Hirsutism

[10]

FK-143

Drug Info

Phase 2

Prostate disease

[11]

Turosteride

Drug Info

Phase 2

Prostate disease

[12]

IZONSTERIDE

Drug Info

Phase 1/2

Hirsutism

[13]

Discontinued Drug(s)

[+] 5 Discontinued Drugs

ONO-3805

Drug Info

Discontinued in Phase 3

Prostate disease

[14]

CS-891B

Drug Info

Discontinued in Phase 2

Alopecia

[15]

MK-0963

Drug Info

Discontinued in Phase 1

Prostate disease

[16]

MK-434

Drug Info

Discontinued in Phase 1

Prostate disease

[17]

GI-197111

Drug Info

Terminated

Alopecia

[18]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 9 Inhibitor drugs

Azelaic Acid

Drug Info

[19]

Dutasteride

Drug Info

[1]

Finasteride

Drug Info

[1]

Dutasteride + tamsulosin

Drug Info

[21]

Epristeride

Drug Info

[22]

Turosteride

Drug Info

[25]

CS-891B

Drug Info

[29]

MK-0963

Drug Info

[4], [30]

MK-434

Drug Info

[4], [31]

Modulator

[+] 5 Modulator drugs

Polyestradiol Phosphate

Drug Info

[20]

FK-143

Drug Info

[23], [24]

IZONSTERIDE

Drug Info

[26], [27]

ONO-3805

Drug Info

[28]

GI-197111

Drug Info

[32]

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target-Related Models and Studies

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Target Validation

Target Validation Info

Target QSAR Model

References

Top

REF 1

The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme Can Urol Assoc J. 2009 Jun;3(3 Suppl 2):S109-14.

REF 2

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7484).

REF 3

Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders. Drugs. 1991 May;41(5):780-98.

REF 4

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 5

REF 6

5alpha-reductase inhibitors in benign prostatic hyperplasia and prostate cancer risk reduction. Best Pract Res Clin Endocrinol Metab. 2008 Apr;22(2):389-402.

REF 7

REF 8

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 9

ClinicalTrials.gov (NCT00090103) Benign Prostatic Hyperplasia Trial With Dutasteride And Tamsulosin Combination Treatment. U.S. National Institutes of Health.

REF 10

Epristeride SmithKline Beecham. IDrugs. 1998 May;1(1):152-7.

REF 11

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003112)

REF 12

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002567)

REF 13

5alpha-reductase activity in the prostate. Urology. 2001 Dec;58(6 Suppl 1):17-24; discussion 24.

REF 14

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003081)

REF 15

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013642)

REF 16

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003374)

REF 17

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005411)

REF 18

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008867)

REF 19

Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid. Br J Dermatol. 1988 Nov;119(5):627-32.

REF 20

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

REF 21

Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).

REF 22

Discovery of a novel hybrid from finasteride and epristeride as 5alpha-reductase inhibitor. Bioorg Med Chem Lett. 2011 Jan 1;21(1):475-8.

REF 23

FK143, a novel nonsteroidal inhibitor of steroid 5 alpha-reductase: (1) In vitro effects on human and animal prostatic enzymes. J Steroid Biochem Mol Biol. 1995 Apr;52(4):357-63.

REF 24

Preventive effect of FK143, a 5alpha-reductase inhibitor, on chemical hepatocarcinogenesis in rats. Clin Cancer Res. 2001 Jul;7(7):2096-104.

REF 25

Hormonal effects of turosteride, a 5 alpha-reductase inhibitor, in the rat. J Steroid Biochem Mol Biol. 1993 Nov;46(5):549-55.

REF 26

Phase I and clinical pharmacology of a type I and II, 5-alpha-reductase inhibitor (LY320236) in prostate cancer: elevation of estradiol as possible... Urology. 2004 Jan;63(1):114-9.

REF 27

Kinetic analysis of LY320236: competitive inhibitor of type I and non-competitive inhibitor of type II human steroid 5alpha-reductase. J Steroid Biochem Mol Biol. 2000 Jan-Feb;72(1-2):13-21.

REF 28

Significant role of 5 alpha-reductase on feedback effects of androgen in rat anterior pituitary cells demonstrated with a nonsteroidal 5 alpha-redu... J Androl. 1994 Nov-Dec;15(6):521-7.

REF 29

The novel drug CS-891 inhibits 5alpha-reductase activity in freshly isolated dermal papilla of human hair follicles. Eur J Dermatol. 2000 Dec;10(8):593-5.

REF 30

Pharmacodynamics of MK-0963, a new 5 alpha-reductase inhibitor: effects on serum androgen concentrations. Clin Pharmacol Ther. 1994 Jan;55(1):50-4.

REF 31

The effects of progesterone, 4,16-androstadien-3-one and MK-434 on the kinetics of pig testis microsomal testosterone-4-ene-5alpha-reductase activity. J Steroid Biochem Mol Biol. 1997 Mar;60(5-6):353-9.

REF 32

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008867)

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