Details of Drug Off-Target (DOT)

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

• DOT Name: Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7)
• Gene Name: CHCHD7
• UniProt ID: CHCH7_HUMAN
• PDB ID: 2LQT
• Pfam ID: PF02297
• Sequence:
  MPSVTQRLRDPDINPCLSESDASTRCLDENNYDRERCSTYFLRYKNCRRFWNSIVMQRRK
  NGVKPFMPTAAERDEILRAVGNMPY
• Reactome Pathway: Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

14 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 Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[15]

1 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 Coiled-coil-helix-coiled-coil-helix domain-containing protein 7 (CHCHD7).	[10]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.