Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRYIO1J)

• DOT Name: COX assembly mitochondrial protein 2 homolog (CMC2)
• Gene Name: CMC2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Hepatitis C virus infection
• UniProt ID: COXM2_HUMAN
• Pfam ID: PF08583
• Sequence:
  MHPDLSPHLHTEECNVLINLLKECHKNHNILKFFGYCNDVDRELRKCLKNEYVENRTKSR
  EHGIAMRKKLFNPPEESEK
• Function: May be involved in cytochrome c oxidase biogenesis.
• Reactome Pathway: Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Daunorubicin	DMQUSBT	Approved	COX assembly mitochondrial protein 2 homolog (CMC2) affects the response to substance of Daunorubicin.	[16]

13 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 COX assembly mitochondrial protein 2 homolog (CMC2).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[7]
Selenium	DM25CGV	Approved	Selenium decreases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[9]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of COX assembly mitochondrial protein 2 homolog (CMC2).	[15]

References

• [1] Prediction of metastatic relapse in node-positive breast cancer: establishment of a clinicogenomic model after FEC100 adjuvant regimen.Breast Cancer Res Treat. 2008 Jun;109(3):491-501. doi: 10.1007/s10549-007-9673-x. Epub 2007 Jul 21.
• [2] Screening HCV genotype-specific epitope peptides based on conserved sequence analysis and B cell epitope prediction in HCV E2 region.Immunol Res. 2018 Feb;66(1):67-73. doi: 10.1007/s12026-017-8962-7.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [10] 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.
• [11] 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.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [16] Mapping genes that contribute to daunorubicin-induced cytotoxicity. Cancer Res. 2007 Jun 1;67(11):5425-33. doi: 10.1158/0008-5472.CAN-06-4431.