Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA0UNHM)

• DOT Name: Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1)
• Synonyms: EC 5.3.3.-
• Gene Name: ECH1
• Related Disease:
  Lung cancer
  Lung carcinoma
• UniProt ID: ECH1_HUMAN
• PDB ID: 2VRE
• EC Number: 5.3.3.-
• Pfam ID: PF00378
• Sequence:
  MAAGIVASRRLRDLLTRRLTGSNYPGLSISLRLTGSSAQEEASGVALGEAPDHSYESLRV
  TSAQKHVLHVQLNRPNKRNAMNKVFWREMVECFNKISRDADCRAVVISGAGKMFTAGIDL
  MDMASDILQPKGDDVARISWYLRDIITRYQETFNVIERCPKPVIAAVHGGCIGGGVDLVT
  ACDIRYCAQDAFFQVKEVDVGLAADVGTLQRLPKVIGNQSLVNELAFTARKMMADEALGS
  GLVSRVFPDKEVMLDAALALAAEISSKSPVAVQSTKVNLLYSRDHSVAESLNYVASWNMS
  MLQTQDLVKSVQATTENKELKTVTFSKL
• Function: Isomerization of 3-trans,5-cis-dienoyl-CoA to 2-trans,4-trans-dienoyl-CoA.
• KEGG Pathway: Peroxisome (hsa04146)
• Reactome Pathway: Peroxisomal protein import (R-HSA-9033241)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Limited	Biomarker	[1]
Lung carcinoma	DISTR26C	Limited	Biomarker	[1]

20 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 Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[11]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[12]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[14]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[16]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[20]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[23]
GW7647	DM9RD0C	Investigative	GW7647 increases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[24]
Farnesol	DMV2X1B	Investigative	Farnesol increases the expression of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[24]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the secretion of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[18]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial (ECH1).	[22]

References

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• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Proteomic and functional analyses reveal a dual molecular mechanism underlying arsenic-induced apoptosis in human multiple myeloma cells. J Proteome Res. 2009 Jun;8(6):3006-19.
• [9] Proteomic analysis of liver cancer cells treated with suberonylanilide hydroxamic acid. Cancer Chemother Pharmacol. 2008 Apr;61(5):791-802.
• [10] 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.
• [11] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [12] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [13] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Calorie restriction-induced changes in the secretome of human adipocytes, comparison with resveratrol-induced secretome effects. Biochim Biophys Acta. 2014 Sep;1844(9):1511-22. doi: 10.1016/j.bbapap.2014.04.023. Epub 2014 May 5.
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• [17] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [18] 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.
• [19] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [20] 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.
• [21] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [22] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [23] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [24] Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells. Toxicol Appl Pharmacol. 2019 Feb 15;365:61-70.