Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4IN0MV)

• DOT Name: Hydroxysteroid dehydrogenase-like protein 2 (HSDL2)
• Synonyms: EC 1.-.-.-; Short chain dehydrogenase/reductase family 13C member 1
• Gene Name: HSDL2
• Related Disease:
  Thyroid gland papillary carcinoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Cholangiocarcinoma
  Congenital contractural arachnodactyly
  Epithelial ovarian cancer
  Glioma
  Liver cancer
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Adult glioblastoma
  Bladder cancer
  Glioblastoma multiforme
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: HSDL2_HUMAN
• PDB ID: 3KVO
• EC Number: 1.-.-.-
• Pfam ID: PF00106 ; PF02036
• Sequence:
  MLPNTGRLAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPKLLGTIYTAAEE
  IEAVGGKALPCIVDVRDEQQISAAVEKAIKKFGGIDILVNNASAISLTNTLDTPTKRLDL
  MMNVNTRGTYLASKACIPYLKKSKVAHILNISPPLNLNPVWFKQHCAYTIAKYGMSMYVL
  GMAEEFKGEIAVNALWPKTAIHTAAMDMLGGPGIESQCRKVDIIADAAYSIFQKPKSFTG
  NFVIDENILKEEGIENFDVYAIKPGHPLQPDFFLDEYPEAVSKKVESTGAVPEFKEEKLQ
  LQPKPRSGAVEETFRIVKDSLSDDVVKATQAIYLFELSGEDGGTWFLDLKSKGGNVGYGE
  PSDQADVVMSMTTDDFVKMFSGKLKPTMAFMSGKLKIKGNMALAIKLEKLMNQMNARL
• Function: Has apparently no steroid dehydrogenase activity.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[2]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Altered Expression	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[4]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Liver cancer	DISDE4BI	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[4]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[4]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[6]
Bladder cancer	DISUHNM0	moderate	Biomarker	[7]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[6]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Hydroxysteroid dehydrogenase-like protein 2 (HSDL2) affects the response to substance of Doxorubicin.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[16]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Hydroxysteroid dehydrogenase-like protein 2 (HSDL2).	[20]

References

• [1] Down-regulated HSDL2 expression suppresses cell proliferation and promotes apoptosis in papillary thyroid carcinoma.Biosci Rep. 2019 Jun 4;39(6):BSR20190425. doi: 10.1042/BSR20190425. Print 2019 Jun 28.
• [2] Lentivirus-mediated overexpression of HSDL2 suppresses cell proliferation and induces apoptosis in cholangiocarcinoma.Onco Targets Ther. 2018 Oct 17;11:7133-7142. doi: 10.2147/OTT.S176410. eCollection 2018.
• [3] Ectopic expression of HSDL2 is related to cell proliferation and prognosis in breast cancer.Cancer Manag Res. 2019 Jul 12;11:6531-6542. doi: 10.2147/CMAR.S205316. eCollection 2019.
• [4] Role of Hydroxysteroid Dehydrogenase-Like 2 (HSDL2) in Human Ovarian Cancer.Med Sci Monit. 2018 Jun 12;24:3997-4008. doi: 10.12659/MSM.909418.
• [5] Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action.PLoS One. 2014 Jul 24;9(7):e102579. doi: 10.1371/journal.pone.0102579. eCollection 2014.
• [6] Lentivirus-mediated silencing of HSDL2 suppresses cell proliferation in human gliomas.Tumour Biol. 2016 Nov;37(11):15065-15077. doi: 10.1007/s13277-016-5402-6. Epub 2016 Sep 22.
• [7] HSDL2 Promotes Bladder Cancer Growth In Vitro and In Vivo.Int J Med Sci. 2019 May 7;16(5):654-659. doi: 10.7150/ijms.31288. eCollection 2019.
• [8] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [9] 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.
• [10] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [11] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [15] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [16] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [17] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [18] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [19] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [21] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.