Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL0DWCO)

• DOT Name: Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2)
• Gene Name: ECHDC2
• Related Disease: Hepatocellular carcinoma
• UniProt ID: ECHD2_HUMAN
• Pfam ID: PF00378
• Sequence:
  MLRVLCLLRPWRPLRARGCASDGAAGGSEIQVRALAGPDQGITEILMNRPSARNALGNVF
  VSELLETLAQLREDRQVRVLLFRSGVKGVFCAGADLKEREQMSEAEVGVFVQRLRGLMND
  IAAFPAPTIAAMDGFALGGGLELALACDLRVAASSAVMGLIETTRGLLPGAGGTQRLPRC
  LGVALAKELIFTGRRLSGTEAHVLGLVNHAVAQNEEGDAAYQRARALAQEILPQAPIAVR
  LGKVAIDRGTEVDIASGMAIEGMCYAQNIPTRDRLEGMAAFREKRTPKFVGK

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[1]

16 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 Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[10]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[14]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Enoyl-CoA hydratase domain-containing protein 2, mitochondrial (ECHDC2).	[16]

References

• [1] Development Of A Three-Gene Prognostic Signature For Hepatitis B Virus Associated Hepatocellular Carcinoma Based On Integrated Transcriptomic Analysis.J Cancer. 2018 Apr 30;9(11):1989-2002. doi: 10.7150/jca.23762. eCollection 2018.
• [2] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [12] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [13] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [14] 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.
• [15] 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.
• [16] 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.