Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKU2RMC)

• DOT Name: Enoyl-CoA hydratase domain-containing protein 3, mitochondrial (ECHDC3)
• Gene Name: ECHDC3
• Related Disease:
  Acute coronary syndrome
  Alzheimer disease
  Cardiovascular disease
• UniProt ID: ECHD3_HUMAN
• PDB ID: 2VX2
• Pfam ID: PF00378
• Sequence:
  MAAVAVLRAFGASGPMCLRRGPWAQLPARFCSRDPAGAGRRESEPRPTSARQLDGIRNIV
  LSNPKKRNALSLAMLKSLQSDILHDADSNDLKVIIISAEGPVFSSGHDLKELTEEQGRDY
  HAEVFQTCSKVMMHIRNHPVPVIAMVNGLAAAAGCQLVASCDIAVASDKSSFATPGVNVG
  LFCSTPGVALARAVPRKVALEMLFTGEPISAQEALLHGLLSKVVPEAELQEETMRIARKI
  ASLSRPVVSLGKATFYKQLPQDLGTAYYLTSQAMVDNLALRDGQEGITAFLQKRKPVWSH
  EPV
• Function: May play a role in fatty acid biosynthesis and insulin sensitivity.
• Tissue Specificity: Expressed in adipocytes . Expressed in blood cells, with higher expression in patients with low coronary lesions .

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute coronary syndrome	DIS7DYEW	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[2]
Cardiovascular disease	DIS2IQDX	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Enoyl-CoA hydratase domain-containing protein 3, mitochondrial (ECHDC3) affects the response to substance of Fluorouracil.	[9]

6 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 Enoyl-CoA hydratase domain-containing protein 3, mitochondrial (ECHDC3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Enoyl-CoA hydratase domain-containing protein 3, mitochondrial (ECHDC3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Enoyl-CoA hydratase domain-containing protein 3, mitochondrial (ECHDC3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Enoyl-CoA hydratase domain-containing protein 3, mitochondrial (ECHDC3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Enoyl-CoA hydratase domain-containing protein 3, mitochondrial (ECHDC3).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Enoyl-CoA hydratase domain-containing protein 3, mitochondrial (ECHDC3).	[8]

References

• [1] The relationship of the oleic acid level and ECHDC3 mRNA expression with the extent of coronary lesion.Lipids Health Dis. 2016 Sep 1;15(1):144. doi: 10.1186/s12944-016-0312-6.
• [2] Association analysis of polymorphisms in STARD6 and near ECHDC3 in Alzheimer's disease patients carrying the APOE 4 Allele.Neuropsychiatr Dis Treat. 2019 Jan 11;15:213-218. doi: 10.2147/NDT.S186705. eCollection 2019.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [9] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.