Details of Drug Off-Target (DOT)

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

• DOT Name: Gap junction gamma-1 protein (GJC1)
• Synonyms: Connexin-45; Cx45; Gap junction alpha-7 protein
• Gene Name: GJC1
• UniProt ID: CXG1_HUMAN
• PDB ID: 3SHW
• Pfam ID: PF00029
• Sequence:
  MSWSFLTRLLEEIHNHSTFVGKIWLTVLIVFRIVLTAVGGESIYYDEQSKFVCNTEQPGC
  ENVCYDAFAPLSHVRFWVFQIILVATPSVMYLGYAIHKIAKMEHGEADKKAARSKPYAMR
  WKQHRALEETEEDNEEDPMMYPEMELESDKENKEQSQPKPKHDGRRRIREDGLMKIYVLQ
  LLARTVFEVGFLIGQYFLYGFQVHPFYVCSRLPCPHKIDCFISRPTEKTIFLLIMYGVTG
  LCLLLNIWEMLHLGFGTIRDSLNSKRRELEDPGAYNYPFTWNTPSAPPGYNIAVKPDQIQ
  YTELSNAKIAYKQNKANTAQEQQYGSHEENLPADLEALQREIRMAQERLDLAVQAYSHQN
  NPHGPREKKAKVGSKAGSNKSTASSKSGDGKTSVWI
• Function: One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
• Reactome Pathway:
  Gap junction assembly (R-HSA-190861)
  Electric Transmission Across Gap Junctions (R-HSA-112303)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Gap junction gamma-1 protein (GJC1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Gap junction gamma-1 protein (GJC1).	[10]

14 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 Gap junction gamma-1 protein (GJC1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Gap junction gamma-1 protein (GJC1).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Gap junction gamma-1 protein (GJC1).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Gap junction gamma-1 protein (GJC1).	[5]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Gap junction gamma-1 protein (GJC1).	[6]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Gap junction gamma-1 protein (GJC1).	[7]
Epanova	DMHEAGL	Approved	Epanova decreases the expression of Gap junction gamma-1 protein (GJC1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Gap junction gamma-1 protein (GJC1).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Gap junction gamma-1 protein (GJC1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Gap junction gamma-1 protein (GJC1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Gap junction gamma-1 protein (GJC1).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Gap junction gamma-1 protein (GJC1).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Gap junction gamma-1 protein (GJC1).	[15]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Gap junction gamma-1 protein (GJC1).	[16]

References

• [1] 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.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [5] 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.
• [6] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [7] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [8] Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells. Breast Cancer Res Treat. 2007 Jan;101(1):7-16. doi: 10.1007/s10549-006-9269-x. Epub 2006 Jul 6.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [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] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [16] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.