Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTTU72V)

• DTT Name: Steroid 5-alpha-reductase 1 (SRD5A1)
• Synonyms: SRD5A1; SR type 1; 5-alpha reductase 1
• Gene Name: SRD5A1
• DTT Type: Clinical trial target; [1]
• Related Disease: Prostate disease [ICD-11: GA91]
• BioChemical Class: CH-CH donor oxidoreductase
• UniProt ID: S5A1_HUMAN
• TTD ID: T70309
• EC Number: EC 1.3.1.22
• 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.
• Reactome Pathway: Androgen biosynthesis (R-HSA-193048)
• BioCyc Pathway: MetaCyc:HS07261-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FR-146687	DMGO45I	Prostate disease	GA91	Phase 2	[1]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MK-386	DM48ELZ	Acne vulgaris	ED80	Discontinued in Phase 2	[2]
AS-601811	DMINF80	Acne vulgaris	ED80	Discontinued in Phase 1	[3], [1]
Bexlosteride	DMH7YD4	N. A.	N. A.	Terminated	[2]

18 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(3-fluoro-4-(4-phenoxybenzoyl)phenyl)acetic acid	DMPHM23	Discovery agent	N.A.	Investigative	[4]
(3-methyl-4-(4-phenoxybenzoyl)phenyl)acetic acid	DMX5CY3	Discovery agent	N.A.	Investigative	[4]
(E)-3-(4-(4-phenoxybenzoyl)phenyl)acrylic acid	DMOWGT3	Discovery agent	N.A.	Investigative	[4]
1,2,5,6-tetrahydro pyrido[1,2-a]quinolin-3-one	DM7BAU2	Discovery agent	N.A.	Investigative	[5]
1-Methyl-5-(4-phenylazo-phenyl)-piperidin-2-one	DM4HS92	Discovery agent	N.A.	Investigative	[6]
1-Methyl-5-phenyl-piperidin-2-one	DMB3JO2	Discovery agent	N.A.	Investigative	[6]
2,3,5,6-Tetrafluoro-4-pentafluorophenylazo-phenol	DMRVYKQ	Discovery agent	N.A.	Investigative	[7]
3,4,5,6-Tetrahydrobenzo[c]quinolizin-3-(4aH)-one	DMKOE9I	Discovery agent	N.A.	Investigative	[5]
4,4'-dihydroxyoctafluoroazobenzene	DM1ONBT	Discovery agent	N.A.	Investigative	[7]
4-(4-phenoxybenzoyl)benzoic acid	DMOHB6U	Discovery agent	N.A.	Investigative	[4]
4-Methyl-5,6-dihydro-pyrido[1,2-a]quinolin-3-one	DM7LPON	Discovery agent	N.A.	Investigative	[5]
4-[4-(benzhydryloxy)benzoyl]benzoic acid	DM8MVE9	Discovery agent	N.A.	Investigative	[4]
4-[4-benzyloxy)benzoyl]benzoic acid	DMQ9IN4	Discovery agent	N.A.	Investigative	[4]
5-(4-Chloro-phenyl)-1-methyl-piperidin-2-one	DMJKAF0	Discovery agent	N.A.	Investigative	[6]
5-(4-Chloro-phenyl)-1-methyl-piperidine-2-thione	DMQB1UI	Discovery agent	N.A.	Investigative	[6]
GP515	DMRUIX3	Discovery agent	N.A.	Investigative	[8]
LY-266111	DMX5H3T	Discovery agent	N.A.	Investigative	[6]
{4-[4-(4-bromophenoxy)benzoyl]phenyl}acetic acid	DMX53OY	Discovery agent	N.A.	Investigative	[4]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Steroid 5-alpha-reductase 1 (SRD5A1) DME Info
• Gene Name: SRD5A1

3 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Oxymetholone	DMFXUT8	Aplastic anemia	3A70	Approved	[9]
Testosterone cypionate	DMC1TEV	Testosterone deficiency	5A81.1	Approved	[10]
Testosterone enanthate	DMB6871	Testosterone deficiency	5A81.1	Approved	[10]

References

• [1] Pharmacokinetics and pharmacodynamics of TF-505, a novel nonsteroidal 5alpha-reductase inhibitor, in normal subjects treated with single or multiple doses. Br J Clin Pharmacol. 2002 Sep;54(3):283-94.
• [2] Synthesis of 8-chloro-benzo[c]quinolizin-3-ones as potent and selective inhibitors of human steroid 5alpha-reductase 1. Bioorg Med Chem Lett. 2000 Feb 21;10(4):353-6.
• [3] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800013228)
• [4] Novel 5alpha-reductase inhibitors: synthesis, structure-activity studies, and pharmacokinetic profile of phenoxybenzoylphenyl acetic acids. J Med Chem. 2006 Jan 26;49(2):748-59.
• [5] Benzo[c]quinolizin-3-ones: a novel class of potent and selective nonsteroidal inhibitors of human steroid 5alpha-reductase 1. J Med Chem. 2000 Oct 5;43(20):3718-35.
• [6] Simple bi- and tricyclic inhibitors of human steroid 5alpha-reductase. Bioorg Med Chem Lett. 2000 Sep 4;10(17):1909-11.
• [7] Hydroxyperfluoroazobenzenes: novel inhibitors of enzymes of androgen biosynthesis. J Med Chem. 1990 Sep;33(9):2452-5.
• [8] 19-nor-10-azasteroids: a novel class of inhibitors for human steroid 5alpha-reductases 1 and 2. J Med Chem. 1997 Mar 28;40(7):1112-29.
• [9] Androgen physiology. Semin Reprod Med. 2006 Apr;24(2):71-7.
• [10] Molecular analysis of the SRD5A1 and SRD5A2 genes in patients with benign prostatic hyperplasia with regard to metabolic parameters and selected hormone levels. Int J Environ Res Public Health. 2017 Oct 30;14(11).