Details of Drug Off-Target (DOT)

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

• DOT Name: 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1)
• Synonyms: 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type I; 3-beta-HSD I; 3-beta-hydroxy-5-ene steroid dehydrogenase; 3-beta-hydroxy-Delta(5)-steroid dehydrogenase; EC 1.1.1.145; 3-beta-hydroxysteroid 3-dehydrogenase; EC 1.1.1.270; Delta-5-3-ketosteroid isomerase; Dihydrotestosterone oxidoreductase; EC 1.1.1.210; Steroid Delta-isomerase; EC 5.3.3.1; Trophoblast antigen FDO161G
• Gene Name: HSD3B1
• UniProt ID: 3BHS1_HUMAN
• EC Number: 1.1.1.145; 1.1.1.210; 1.1.1.270; 5.3.3.1
• Pfam ID: PF01073
• Sequence:
  MTGWSCLVTGAGGFLGQRIIRLLVKEKELKEIRVLDKAFGPELREEFSKLQNKTKLTVLE
  GDILDEPFLKRACQDVSVIIHTACIIDVFGVTHRESIMNVNVKGTQLLLEACVQASVPVF
  IYTSSIEVAGPNSYKEIIQNGHEEEPLENTWPAPYPHSKKLAEKAVLAANGWNLKNGGTL
  YTCALRPMYIYGEGSRFLSASINEALNNNGILSSVGKFSTVNPVYVGNVAWAHILALRAL
  QDPKKAPSIRGQFYYISDDTPHQSYDNLNYTLSKEFGLRLDSRWSFPLSLMYWIGFLLEI
  VSFLLRPIYTYRPPFNRHIVTLSNSVFTFSYKKAQRDLAYKPLYSWEEAKQKTVEWVGSL
  VDRHKETLKSKTQ
• Function: A bifunctional enzyme responsible for the oxidation and isomerization of 3beta-hydroxy-Delta(5)-steroid precursors to 3-oxo-Delta(4)-steroids, an essential step in steroid hormone biosynthesis. Specifically catalyzes the conversion of pregnenolone to progesterone, 17alpha-hydroxypregnenolone to 17alpha-hydroxyprogesterone, dehydroepiandrosterone (DHEA) to 4-androstenedione, and androstenediol to testosterone. Additionally, catalyzes the interconversion between 3beta-hydroxy and 3-oxo-5alpha-androstane steroids controlling the bioavalability of the active forms. Specifically converts dihydrotestosterone to its inactive form 5alpha-androstanediol, that does not bind androgen receptor/AR. Also converts androstanedione, a precursor of testosterone and estrone, to epiandrosterone. Expected to use NAD(+) as preferred electron donor for the 3beta-hydroxy-steroid dehydrogenase activity and NADPH for the 3-ketosteroid reductase activity (Probable).
• Tissue Specificity: Placenta and skin . Predominantly expressed in mammary gland tissue.
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Metabolic pathways (hsa01100)
  Ovarian steroidogenesis (hsa04913)
  Aldosterone synthesis and secretion (hsa04925)
  Cortisol synthesis and secretion (hsa04927)
  Cushing syndrome (hsa04934)
• Reactome Pathway:
  Mineralocorticoid biosynthesis (R-HSA-193993)
  Glucocorticoid biosynthesis (R-HSA-194002)
  Androgen biosynthesis (R-HSA-193048)
• BioCyc Pathway: MetaCyc:HS08829-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1) increases the chemical synthesis of Progesterone.	[24]
4-ANDROSTENE-3-17-DIONE	DMSE8NU	Investigative	3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1) increases the chemical synthesis of 4-ANDROSTENE-3-17-DIONE.	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the activity of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[10]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[3]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[11]
Vitamin C	DMXJ7O8	Approved	Vitamin C increases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[12]
Bosentan	DMIOGBU	Approved	Bosentan affects the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[14]
Mitotane	DMU1GX0	Approved	Mitotane decreases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[15]
Hexachlorophene	DMLKSE0	Approved	Hexachlorophene decreases the activity of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[17]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[20]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[22]
NSC-1771	DMNXDGQ	Investigative	NSC-1771 decreases the activity of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[16]
1,4-Dithiothreitol	DMIFOXE	Investigative	1,4-Dithiothreitol increases the activity of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[16]
G6976	DMEZO4M	Investigative	G6976 increases the expression of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[23]
2,3-dichloro-1,4-naphthoquinone	DMPCGSD	Investigative	2,3-dichloro-1,4-naphthoquinone decreases the activity of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[5]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[21]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone affects the binding of 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1 (HSD3B1).	[13]

References

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• [10] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
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