Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRQTK84)

• DOT Name: Enoyl-CoA delta isomerase 1, mitochondrial (ECI1)
• Synonyms: EC 5.3.3.8; 3,2-trans-enoyl-CoA isomerase; Delta(3),Delta(2)-enoyl-CoA isomerase; D3,D2-enoyl-CoA isomerase; Dodecenoyl-CoA isomerase
• Gene Name: ECI1
• Related Disease:
  Achalasia
  Dilated cardiomyopathy 1A
  Ductal breast carcinoma in situ
  Hydrocephalus
  Polycystic ovarian syndrome
  Gastroesophageal reflux disease
  Peptic esophagitis
  Subarachnoid hemorrhage
• UniProt ID: ECI1_HUMAN
• PDB ID: 1SG4
• EC Number: 5.3.3.8
• Pfam ID: PF00378
• Sequence:
  MALVASVRVPARVLLRAGARLPGAALGRTERAAGGGDGARRFGSQRVLVEPDAGAGVAVM
  KFKNPPVNSLSLEFLTELVISLEKLENDKSFRGVILTSDRPGVFSAGLDLTEMCGRSPAH
  YAGYWKAVQELWLRLYQSNLVLVSAINGACPAGGCLVALTCDYRILADNPRYCIGLNETQ
  LGIIAPFWLKDTLENTIGHRAAERALQLGLLFPPAEALQVGIVDQVVPEEQVQSTALSAI
  AQWMAIPDHARQLTKAMMRKATASRLVTQRDADVQNFVSFISKDSIQKSLQMYLERLKEE
  KG
• Function: Key enzyme of fatty acid beta-oxidation (Probable). Able to isomerize both 3-cis (3Z) and 3-trans (3E) double bonds into the 2-trans (2E) form in a range of enoyl-CoA species, with a preference for (3Z)-enoyl-CoAs over (3E)-enoyl-CoAs. The catalytic efficiency of this enzyme is not affected by the fatty acyl chain length.
• Tissue Specificity: Expressed in liver (at protein level).
• KEGG Pathway: Fatty acid degradation (hsa00071)
• Reactome Pathway: mitochondrial fatty acid beta-oxidation of unsaturated fatty acids (R-HSA-77288)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Achalasia	DISK845N	Strong	Biomarker	[1]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[2]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Genetic Variation	[2]
Hydrocephalus	DISIZUF7	Strong	Genetic Variation	[3]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[4]
Gastroesophageal reflux disease	DISQ8G5S	Limited	Genetic Variation	[5]
Peptic esophagitis	DISJSGBZ	Limited	Biomarker	[6]
Subarachnoid hemorrhage	DISI7I8Y	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Enoyl-CoA delta isomerase 1, mitochondrial (ECI1) decreases the response to substance of Arsenic trioxide.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[15]

12 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 Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[17]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[19]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Enoyl-CoA delta isomerase 1, mitochondrial (ECI1).	[20]

References

• [1] Multiple Rapid Swallows (MRS) Complements Single-Swallow (SS) Analysis for High-Resolution Esophageal Manometry (HREM).Dig Dis Sci. 2019 Aug;64(8):2206-2213. doi: 10.1007/s10620-019-05545-2. Epub 2019 Feb 25.
• [2] Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection.J Pathol. 2012 May;227(1):42-52. doi: 10.1002/path.3990. Epub 2012 Mar 21.
• [3] Incidence and impact of sepsis on long-term outcomes after subarachnoid hemorrhage: a prospective observational study.Ann Intensive Care. 2019 Aug 20;9(1):94. doi: 10.1186/s13613-019-0562-3.
• [4] Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols.Front Pharmacol. 2017 Jun 8;8:341. doi: 10.3389/fphar.2017.00341. eCollection 2017.
• [5] Tailored modern GERD therapy - steps towards the development of an aid to guide personalized anti-reflux surgery.Sci Rep. 2019 Dec 16;9(1):19174. doi: 10.1038/s41598-019-55510-2.
• [6] Impact of reflux esophagitis on the esophageal function before and after laparoscopic fundoplication.Esophagus. 2018 Oct;15(4):224-230. doi: 10.1007/s10388-018-0618-8. Epub 2018 Apr 26.
• [7] The Role of ABO Blood Group in Cerebral Vasospasm, Associated Intracranial Hemorrhage, and Delayed Cerebral Ischemia in 470 Patients with Subarachnoid Hemorrhage.World Neurosurg. 2017 Jan;97:532-537. doi: 10.1016/j.wneu.2016.10.065. Epub 2016 Oct 21.
• [8] 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.
• [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] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [20] Ochratoxin a lowers mRNA levels of genes encoding for key proteins of liver cell metabolism. Cancer Genomics Proteomics. 2008 Nov-Dec;5(6):319-32.
• [21] The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.