Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3VIM3B)

• DOT Name: Estradiol 17-beta-dehydrogenase 11 (HSD17B11)
• Synonyms: EC 1.1.1.62; 17-beta-hydroxysteroid dehydrogenase 11; 17-beta-HSD 11; 17bHSD11; 17betaHSD11; 17-beta-hydroxysteroid dehydrogenase XI; 17-beta-HSD XI; 17betaHSDXI; Cutaneous T-cell lymphoma-associated antigen HD-CL-03; CTCL-associated antigen HD-CL-03; Dehydrogenase/reductase SDR family member 8; Retinal short-chain dehydrogenase/reductase 2; retSDR2; Short chain dehydrogenase/reductase family 16C member 2
• Gene Name: HSD17B11
• UniProt ID: DHB11_HUMAN
• PDB ID: 1YB1
• EC Number: 1.1.1.62
• Pfam ID: PF00106
• Sequence:
  MKFLLDILLLLPLLIVCSLESFVKLFIPKRRKSVTGEIVLITGAGHGIGRLTAYEFAKLK
  SKLVLWDINKHGLEETAAKCKGLGAKVHTFVVDCSNREDIYSSAKKVKAEIGDVSILVNN
  AGVVYTSDLFATQDPQIEKTFEVNVLAHFWTTKAFLPAMTKNNHGHIVTVASAAGHVSVP
  FLLAYCSSKFAAVGFHKTLTDELAALQITGVKTTCLCPNFVNTGFIKNPSTSLGPTLEPE
  EVVNRLMHGILTEQKMIFIPSSIAFLTTLERILPERFLAVLKRKISVKFDAVIGYKMKAQ
• Function: Can convert androstan-3-alpha,17-beta-diol (3-alpha-diol) to androsterone in vitro, suggesting that it may participate in androgen metabolism during steroidogenesis. May act by metabolizing compounds that stimulate steroid synthesis and/or by generating metabolites that inhibit it. Has no activity toward DHEA (dehydroepiandrosterone), or A-dione (4-androste-3,17-dione), and only a slight activity toward testosterone to A-dione. Tumor-associated antigen in cutaneous T-cell lymphoma.
• Tissue Specificity: Present at high level in steroidogenic cells such as syncytiotrophoblasts, sebaceous gland, Leydig cells, and granulosa cells of the dominant follicle and corpus luteum. In lung, it is detected in the ciliated epithelium and in acini of adult trachea, in bronchioles, but not in alveoli. In the eye, it is detected in the nonpigmented epithelium of the ciliary body and, at lower level, in the inner nuclear layer of the retina (at protein level). Widely expressed. Highly expressed in retina, pancreas, kidney, liver, lung, adrenal, small intestine, ovary and heart.
• KEGG Pathway:
  Steroid hormone biosynthesis (hsa00140)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Estrogen biosynthesis (R-HSA-193144)

Molecular Interaction Atlas (MIA) of This DOT

19 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 Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[10]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[12]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[15]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[16]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of Estradiol 17-beta-dehydrogenase 11 (HSD17B11).	[18]

References

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• [13] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [14] 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.
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