Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPDMCC4)

• DOT Name: Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1)
• Synonyms: Short chain dehydrogenase/reductase family 12C member 3
• Gene Name: HSDL1
• Related Disease:
  Melanocytic nevus
  Prostate cancer
  Prostate carcinoma
  CHILD syndrome
• UniProt ID: HSDL1_HUMAN
• Pfam ID: PF00106
• Sequence:
  MAAVDSFYLLYREIARSCNCYMEALALVGAWYTARKSITVICDFYSLIRLHFIPRLGSRA
  DLIKQYGRWAVVSGATDGIGKAYAEELASRGLNIILISRNEEKLQVVAKDIADTYKVETD
  IIVADFSSGREIYLPIREALKDKDVGILVNNVGVFYPYPQYFTQLSEDKLWDIINVNIAA
  ASLMVHVVLPGMVERKKGAIVTISSGSCCKPTPQLAAFSASKAYLDHFSRALQYEYASKG
  IFVQSLIPFYVATSMTAPSNFLHRCSWLVPSPKVYAHHAVSTLGISKRTTGYWSHSIQFL
  FAQYMPEWLWVWGANILNRSLRKEALSCTA
• Tissue Specificity: Highly expressed in testis and ovary. Also detected in thyroid, spinal cord, adrenal gland, heart, placenta, skeletal muscle, small intestine, colon, spleen, prostate and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Melanocytic nevus	DISYS32D	Strong	Genetic Variation	[1]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
CHILD syndrome	DIS9F5U7	Limited	Genetic Variation	[1]

9 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 Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[13]

3 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 Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Inactive hydroxysteroid dehydrogenase-like protein 1 (HSDL1).	[14]

References

• [1] CHILD syndrome: A modified pathogenesis-targeted therapeutic approach.Am J Med Genet A. 2018 Mar;176(3):733-738. doi: 10.1002/ajmg.a.38619. Epub 2018 Feb 2.
• [2] A novel human hydroxysteroid dehydrogenase like 1 gene (HSDL1) is highly expressed in reproductive tissues.Mol Biol Rep. 2001;28(4):185-91. doi: 10.1023/a:1015726217890.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] 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.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.