Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3K7HY5)

• DOT Name: 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)
• Synonyms: 17-beta-HSD 2; 20 alpha-hydroxysteroid dehydrogenase; 20-alpha-HSD; E2DH; Estradiol 17-beta-dehydrogenase 2; EC 1.1.1.62; Microsomal 17-beta-hydroxysteroid dehydrogenase; Short chain dehydrogenase/reductase family 9C member 2; Testosterone 17-beta-dehydrogenase; EC 1.1.1.239
• Gene Name: HSD17B2
• UniProt ID: DHB2_HUMAN
• EC Number: 1.1.1.239; 1.1.1.62
• Pfam ID: PF00106
• Sequence:
  MSTFFSDTAWICLAVPTVLCGTVFCKYKKSSGQLWSWMVCLAGLCAVCLLILSPFWGLIL
  FSVSCFLMYTYLSGQELLPVDQKAVLVTGGDCGLGHALCKYLDELGFTVFAGVLNENGPG
  AEELRRTCSPRLSVLQMDITKPVQIKDAYSKVAAMLQDRGLWAVINNAGVLGFPTDGELL
  LMTDYKQCMAVNFFGTVEVTKTFLPLLRKSKGRLVNVSSMGGGAPMERLASYGSSKAAVT
  MFSSVMRLELSKWGIKVASIQPGGFLTNIAGTSDKWEKLEKDILDHLPAEVQEDYGQDYI
  LAQRNFLLLINSLASKDFSPVLRDIQHAILAKSPFAYYTPGKGAYLWICLAHYLPIGIYD
  YFAKRHFGQDKPMPRALRMPNYKKKAT
• Function: Catalyzes the NAD-dependent oxidation of the highly active 17beta-hydroxysteroids, such as estradiol (E2), testosterone (T), and dihydrotestosterone (DHT), to their less active forms and thus regulates the biological potency of these steroids. Oxidizes estradiol to estrone, testosterone to androstenedione, and dihydrotestosterone to 5alpha-androstan-3,17-dione. Also has 20-alpha-HSD activity.
• Tissue Specificity: Expressed in placenta.
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Metabolic pathways (hsa01100)
  Ovarian steroidogenesis (hsa04913)
• Reactome Pathway: Estrogen biosynthesis (R-HSA-193144)
• BioCyc Pathway: MetaCyc:HS01540-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Biotransformations of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Estrone	DM5T6US	Approved	17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) increases the chemical synthesis of Estrone.	[23]
Prasterone	DM67VKL	Approved	17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) increases the chemical synthesis of Prasterone.	[23]
HE2100	DMCP2KH	Discontinued in Phase 1	17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) increases the chemical synthesis of HE2100.	[23]
4-ANDROSTENE-3-17-DIONE	DMSE8NU	Investigative	17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) increases the chemical synthesis of 4-ANDROSTENE-3-17-DIONE.	[23]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etretinate	DM2CZFA	Approved	17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) affects the metabolism of Etretinate.	[24]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Steroid derivative 1	DMB0NVQ	Patented	17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) decreases the response to substance of Steroid derivative 1.	[25]

23 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 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[1]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[11]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[12]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[14]
Plicamycin	DM7C8YV	Approved	Plicamycin decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[15]
Dydrogesterone	DMAKIDV	Approved	Dydrogesterone decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[12]
Oestradiol valerate and dienogest	DMZK0FQ	Approved	Oestradiol valerate and dienogest decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[12]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[9]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[18]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetoacetyl-Coenzyme A	DM3HYU8	Investigative	Acetoacetyl-Coenzyme A affects the binding of 17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2).	[22]

References

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• [24] Transgenic male mice expressing human hydroxysteroid dehydrogenase 2 indicate a role for the enzyme independent of its action on sex steroids. Endocrinology. 2007 Aug;148(8):3827-36. doi: 10.1210/en.2007-0365. Epub 2007 May 17.
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