Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG435Q9)

• DOT Name: Peroxisomal 2,4-dienoyl-CoA reductase (DECR2)
• Synonyms: pDCR; EC 1.3.1.124; 2,4-dienoyl-CoA reductase 2; Short chain dehydrogenase/reductase family 17C member 1
• Gene Name: DECR2
• UniProt ID: DECR2_HUMAN
• PDB ID: 4FC6; 4FC7
• EC Number: 1.3.1.124
• Pfam ID: PF13561
• Sequence:
  MAQPPPDVEGDDCLPAYRHLFCPDLLRDKVAFITGGGSGIGFRIAEIFMRHGCHTVIASR
  SLPRVLTAARKLAGATGRRCLPLSMDVRAPPAVMAAVDQALKEFGRIDILINCAAGNFLC
  PAGALSFNAFKTVMDIDTSGTFNVSRVLYEKFFRDHGGVIVNITATLGNRGQALQVHAGS
  AKAAVDAMTRHLAVEWGPQNIRVNSLAPGPISGTEGLRRLGGPQASLSTKVTASPLQRLG
  NKTEIAHSVLYLASPLASYVTGAVLVADGGAWLTFPNGVKGLPDFASFSAKL
• Function: Auxiliary enzyme of beta-oxidation. Participates in the degradation of unsaturated fatty enoyl-CoA esters having double bonds in both even- and odd-numbered positions in peroxisome. Catalyzes the NADP-dependent reduction of 2,4-dienoyl-CoA to yield trans-3-enoyl-CoA. Has activity towards short and medium chain 2,4-dienoyl-CoAs, but also towards 2,4,7,10,13,16,19-docosaheptaenoyl-CoA, suggesting that it does not constitute a rate limiting step in the peroxisomal degradation of docosahexaenoic acid.
• KEGG Pathway: Peroxisome (hsa04146)
• Reactome Pathway:
  Peroxisomal protein import (R-HSA-9033241)
  Beta-oxidation of very long chain fatty acids (R-HSA-390247)

Molecular Interaction Atlas (MIA) of This DOT

2 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 Peroxisomal 2,4-dienoyl-CoA reductase (DECR2).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Peroxisomal 2,4-dienoyl-CoA reductase (DECR2).	[5]

7 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 Peroxisomal 2,4-dienoyl-CoA reductase (DECR2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Peroxisomal 2,4-dienoyl-CoA reductase (DECR2).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peroxisomal 2,4-dienoyl-CoA reductase (DECR2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Peroxisomal 2,4-dienoyl-CoA reductase (DECR2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Peroxisomal 2,4-dienoyl-CoA reductase (DECR2).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Peroxisomal 2,4-dienoyl-CoA reductase (DECR2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Peroxisomal 2,4-dienoyl-CoA reductase (DECR2).	[9]

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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] 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.
• [6] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [7] 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.
• [8] 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.
• [9] 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.