Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTG0NFD)

• DOT Name: 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2)
• Synonyms: EC 1.3.1.22; 5 alpha-SR2; SR type 2; Steroid 5-alpha-reductase 2; S5AR 2; Type II 5-alpha reductase
• Gene Name: SRD5A2
• Related Disease: 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency
• UniProt ID: S5A2_HUMAN
• PDB ID: 7BW1
• EC Number: 1.3.1.22
• Pfam ID: PF02544
• Sequence:
  MQVQCQQSPVLAGSATLVALGALALYVAKPSGYGKHTESLKPAATRLPARAAWFLQELPS
  FAVPAGILARQPLSLFGPPGTVLLGLFCLHYFHRTFVYSLLNRGRPYPAILILRGTAFCT
  GNGVLQGYYLIYCAEYPDGWYTDIRFSLGVFLFILGMGINIHSDYILRQLRKPGEISYRI
  PQGGLFTYVSGANFLGEIIEWIGYALATWSLPALAFAFFSLCFLGLRAFHHHRFYLKMFE
  DYPKSRKALIPFIF
• Function: Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
• Tissue Specificity: Expressed in high levels in the prostate and many other androgen-sensitive tissues.
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Metabolic pathways (hsa01100)
  Prostate cancer (hsa05215)
• Reactome Pathway: Androgen biosynthesis (R-HSA-193048)
• BioCyc Pathway: MetaCyc:HS00619-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency	DISO74X3	Strong	Autosomal recessive	[1]

19 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[2]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[4]
Progesterone	DMUY35B	Approved	Progesterone decreases the activity of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[5]
Propofol	DMB4OLE	Approved	Propofol decreases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[6]
Flutamide	DMK0O7U	Approved	Flutamide decreases the activity of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[7]
Dutasteride	DMQ4TJK	Approved	Dutasteride decreases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[8]
Methyltestosterone	DMWLFGO	Approved	Methyltestosterone decreases the activity of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[7]
Finasteride	DMWV3TZ	Approved	Finasteride decreases the activity of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[7]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[9]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[9]
Guaiacol	DMN4E7T	Phase 3	Guaiacol decreases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[9]
Puerarin	DMJIMXH	Phase 2	Puerarin decreases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[10]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the activity of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[11]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid decreases the expression of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[9]
MANGIFERIN	DMWAF5Z	Investigative	MANGIFERIN decreases the activity of 3-oxo-5-alpha-steroid 4-dehydrogenase 2 (SRD5A2).	[12]

References

• [1] Brief report: the molecular basis of steroid 5 alpha-reductase deficiency in a large Dominican kindred. N Engl J Med. 1992 Oct 22;327(17):1216-9. doi: 10.1056/NEJM199210223271706.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Effects of low dose treatment of tributyltin on the regulation of estrogen receptor functions in MCF-7 cells. Toxicol Appl Pharmacol. 2013 Jun 1;269(2):176-86.
• [4] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [5] Molecular interactions of progesterone derivatives with 5 alpha-reductase types 1 and 2 and androgen receptors. Steroids. 2010 Jul;75(7):499-505.
• [6] Propofol suppresses proliferation, migration, invasion, and tumor growth of liver cancer cells via suppressing cancer susceptibility candidate 9/phosphatase and tensin homolog/AKT serine/threonine kinase/mechanistic target of rapamycin kinase axis. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271211065972. doi: 10.1177/09603271211065972.
• [7] Effects of various pesticides on human 5alpha-reductase activity in prostate and LNCaP cells. Toxicol In Vitro. 2007 Apr;21(3):502-8.
• [8] Dutasteride affects progesterone metabolizing enzyme activity/expression in human breast cell lines resulting in suppression of cell proliferation and detachment. J Steroid Biochem Mol Biol. 2006 Aug;100(4-5):129-40.
• [9] Examining the genomic influence of skin antioxidants in vitro. Mediators Inflamm. 2010;2010.
• [10] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [11] Effects of butyltins on human 5alpha-reductase type 1 and type 2 activity. Steroids. 2002 Sep;67(10):859-67.
• [12] Establishment of a novel model for studying the effects of extracts of Chinese herb medicine on human type II 5alpha-reductase in vitro. Yakugaku Zasshi. 2010 Sep;130(9):1207-14.