Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT2A0DR)

• DTT Name: Oxo-5-alpha-steroid 4-dehydrogenase (SRD5A)
• Synonyms: Steroid 5-alpha-reductase; SR; S5AR; 3-oxo-5-alpha-steroid 4-dehydrogenase
• Gene Name: SRD5A1
• DTT Type: Successful target; [1]
• BioChemical Class: CH-CH donor oxidoreductase
• UniProt ID: S5A1_HUMAN ; S5A2_HUMAN ; PORED_HUMAN
• TTD ID: T27265
• Sequence:
  MATATGVAEERLLAALAYLQCAVGCAVFARNRQTNSVYGRHALPSHRLRVPARAAWVVQE
  LPSLALPLYQYASESAPRLRSAPNCILLAMFLVHYGHRCLIYPFLMRGGKPMPLLACTMA
  IMFCTCNGYLQSRYLSHCAVYADDWVTDPRFLIGFGLWLTGMLINIHSDHILRNLRKPGD
  TGYKIPRGGLFEYVTAANYFGEIMEWCGYALASWSVQGAAFAFFTFCFLSGRAKEHHEWY
  LRKFEEYPKFRKIIIPFLF
• 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.
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Androgen biosynthesis (R-HSA-193048)
• BioCyc Pathway: MetaCyc:HS07261-MON

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Azelaic Acid	DMHVL0J	Acne vulgaris	ED80	Approved	[2]
Dutasteride	DMQ4TJK	Benign prostatic hyperplasia	GA90	Approved	[1]
Finasteride	DMWV3TZ	Baldness, male pattern		Approved	[1]
Polyestradiol Phosphate	DM0PMGJ	Prostate cancer	2C82.0	Approved	[3]

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dutasteride + tamsulosin	DM6P8HU	Benign prostatic hyperplasia	GA90	Phase 3	[4]
Epristeride	DM35T1O	Hirsutism	ED72	Phase 3	[5]
FK-143	DMEL15U	Prostate disease	GA91	Phase 2	[6]
Turosteride	DMW7PFS	Prostate disease	GA91	Phase 2	[7]
IZONSTERIDE	DM3KXMG	Hirsutism	ED72	Phase 1/2	[8]

5 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ONO-3805	DM1RKWV	Prostate disease	GA91	Discontinued in Phase 3	[9]
CS-891B	DM17I8O	Alopecia	ED70	Discontinued in Phase 2	[10]
MK-0963	DMNAJGK	Prostate disease	GA91	Discontinued in Phase 1	[11]
MK-434	DMERKWM	Prostate disease	GA91	Discontinued in Phase 1	[12]
GI-197111	DM6HZU1	Alopecia	ED70	Terminated	[13]

References

• [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.
• [2] Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid. Br J Dermatol. 1988 Nov;119(5):627-32.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [5] Discovery of a novel hybrid from finasteride and epristeride as 5alpha-reductase inhibitor. Bioorg Med Chem Lett. 2011 Jan 1;21(1):475-8.
• [6] 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.
• [7] Hormonal effects of turosteride, a 5 alpha-reductase inhibitor, in the rat. J Steroid Biochem Mol Biol. 1993 Nov;46(5):549-55.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Pharmacodynamics of MK-0963, a new 5 alpha-reductase inhibitor: effects on serum androgen concentrations. Clin Pharmacol Ther. 1994 Jan;55(1):50-4.
• [12] 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.
• [13] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008867)