Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8YRGCM)

• DOT Name: Dehydrogenase/reductase SDR family member 1 (DHRS1)
• Synonyms: EC 1.1.1.-; Short chain dehydrogenase/reductase family 19C member 1; Protein SDR19C1
• Gene Name: DHRS1
• UniProt ID: DHRS1_HUMAN
• PDB ID: 2QQ5
• EC Number: 1.1.1.-
• Pfam ID: PF00106
• Sequence:
  MAAPMNGQVCVVTGASRGIGRGIALQLCKAGATVYITGRHLDTLRVVAQEAQSLGGQCVP
  VVCDSSQESEVRSLFEQVDREQQGRLDVLVNNAYAGVQTILNTRNKAFWETPASMWDDIN
  NVGLRGHYFCSVYGARLMVPAGQGLIVVISSPGSLQYMFNVPYGVGKAACDKLAADCAHE
  LRRHGVSCVSLWPGIVQTELLKEHMAKEEVLQDPVLKQFKSAFSSAETTELSGKCVVALA
  TDPNILSLSGKVLPSCDLARRYGLRDVDGRPVQDYLSLSSVLSHVSGLGWLASYLPSFLR
  VPKWIIALYTSKF
• Function: NADPH-dependent oxidoreductase which catalyzes the reduction of steroids (estrone, androstene-3,17-dione and cortisone) as well as prostaglandin E1, isatin and xenobiotics in vitro. May have a role in steroid and/or xenobiotic metabolism.
• Tissue Specificity: Detected in heart, liver, adrenal glands, and at low levels in skeletal muscle, kidney, pancreas and brain.

Molecular Interaction Atlas (MIA) of This DOT

1 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 Dehydrogenase/reductase SDR family member 1 (DHRS1).	[1]

11 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 Dehydrogenase/reductase SDR family member 1 (DHRS1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Dehydrogenase/reductase SDR family member 1 (DHRS1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Dehydrogenase/reductase SDR family member 1 (DHRS1).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Dehydrogenase/reductase SDR family member 1 (DHRS1).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Dehydrogenase/reductase SDR family member 1 (DHRS1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Dehydrogenase/reductase SDR family member 1 (DHRS1).	[7]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Dehydrogenase/reductase SDR family member 1 (DHRS1).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Dehydrogenase/reductase SDR family member 1 (DHRS1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Dehydrogenase/reductase SDR family member 1 (DHRS1).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Dehydrogenase/reductase SDR family member 1 (DHRS1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Dehydrogenase/reductase SDR family member 1 (DHRS1).	[12]

References

• [1] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [2] 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.
• [3] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.