Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV7VOV3)

• DOT Name: 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7)
• Synonyms: 17-beta-hydroxysteroid dehydrogenase 7; 17-beta-HSD 7; 3-keto-steroid reductase; EC 1.1.1.270; Dihydrotestosterone oxidoreductase; EC 1.1.1.210; Estradiol 17-beta-dehydrogenase 7; EC 1.1.1.62; Short chain dehydrogenase/reductase family 37C member 1
• Gene Name: HSD17B7
• UniProt ID: DHB7_HUMAN
• EC Number: 1.1.1.210; 1.1.1.270; 1.1.1.62
• Pfam ID: PF00106
• Sequence:
  MRKVVLITGASSGIGLALCKRLLAEDDELHLCLACRNMSKAEAVCAALLASHPTAEVTIV
  QVDVSNLQSVFRASKELKQRFQRLDCIYLNAGIMPNPQLNIKALFFGLFSRKVIHMFSTA
  EGLLTQGDKITADGLQEVFETNVFGHFILIRELEPLLCHSDNPSQLIWTSSRSARKSNFS
  LEDFQHSKGKEPYSSSKYATDLLSVALNRNFNQQGLYSNVACPGTALTNLTYGILPPFIW
  TLLMPAILLLRFFANAFTLTPYNGTEALVWLFHQKPESLNPLIKYLSATTGFGRNYIMTQ
  KMDLDEDTAEKFYQKLLELEKHIRVTIQKTDNQARLSGSCL
• Function: Bifunctional enzyme involved in steroid-hormone metabolism and cholesterol biosynthesis. Catalyzes the NADP(H)-dependent reduction of estrogens and androgens and regulates the biological potency of these steroids. Converts estrone (E1) to a more potent estrogen, 17beta-estradiol (E2). Converts dihydrotestosterone (DHT) to its inactive form 5a-androstane-3b,17b-diol. Converts moderately progesterone to 3beta-hydroxypregn-4-ene-20-one, leading to its inactivation. Additionally, participates in the post-squalene cholesterol biosynthesis, as a 3-ketosteroid reductase ; [Isoform 3]: Does not have enzymatic activities toward E1 and DHT.
• Tissue Specificity: Highly expressed in adrenal gland, liver, lung and thymus. Expressed in breast, ovaries, pituitary gland, pregnant uterus, prostate, kidney, lymph node, small intestine, spinal cord and trachea. Weakly expressed in all other tissues tested.; [Isoform 3]: Expressed in eye ciliary epithelial cells and neuroendocrine cells.
• KEGG Pathway:
  Steroid biosynthesis (hsa00100)
  Steroid hormone biosynthesis (hsa00140)
  Metabolic pathways (hsa01100)
  Ovarian steroidogenesis (hsa04913)
• Reactome Pathway: Cholesterol biosynthesis (R-HSA-191273)
• BioCyc Pathway: MetaCyc:HS05604-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estrone	DM5T6US	Approved	3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7) increases the chemical synthesis of Estrone.	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[10]
Nicotine	DMWX5CO	Approved	Nicotine increases the splicing of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[11]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[12]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[13]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[14]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[17]
UNC0379	DMD1E4J	Preclinical	UNC0379 increases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[20]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7).	[21]

References

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• [21] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
• [22] Steroid signalling in the ovarian surface epithelium. Trends Endocrinol Metab. 2005 Sep;16(7):327-33.