Details of Drug Off-Target (DOT)

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

• DOT Name: Chromobox protein homolog 7 (CBX7)
• Gene Name: CBX7
• UniProt ID: CBX7_HUMAN
• PDB ID: 2K1B; 2L12; 2L1B; 3GS2; 4MN3; 5EPJ; 6V2R
• Pfam ID: PF17218 ; PF00385
• Sequence:
  MELSAIGEQVFAVESIRKKRVRKGKVEYLVKWKGWPPKYSTWEPEEHILDPRLVMAYEEK
  EERDRASGYRKRGPKPKRLLLQRLYSMDLRSSHKAKGKEKLCFSLTCPLGSGSPEGVVKA
  GAPELVDKGPLVPTLPFPLRKPRKAHKYLRLSRKKFPPRGPNLESHSHRRELFLQEPPAP
  DVLQAAGEWEPAAQPPEEEADADLAEGPPPWTPALPSSEVTVTDITANSITVTFREAQAA
  EGFFRDRSGKF
• Function: Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Promotes histone H3 trimethylation at 'Lys-9' (H3K9me3). Binds to trimethylated lysine residues in histones, and possibly also other proteins. Regulator of cellular lifespan by maintaining the repression of CDKN2A, but not by inducing telomerase activity.
• KEGG Pathway: Polycomb repressive complex (hsa03083)

Molecular Interaction Atlas (MIA) of This DOT

17 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 Chromobox protein homolog 7 (CBX7).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Chromobox protein homolog 7 (CBX7).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Chromobox protein homolog 7 (CBX7).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Chromobox protein homolog 7 (CBX7).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Chromobox protein homolog 7 (CBX7).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Chromobox protein homolog 7 (CBX7).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Chromobox protein homolog 7 (CBX7).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Chromobox protein homolog 7 (CBX7).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Chromobox protein homolog 7 (CBX7).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Chromobox protein homolog 7 (CBX7).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Chromobox protein homolog 7 (CBX7).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Chromobox protein homolog 7 (CBX7).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Chromobox protein homolog 7 (CBX7).	[13]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Chromobox protein homolog 7 (CBX7).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Chromobox protein homolog 7 (CBX7).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Chromobox protein homolog 7 (CBX7).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Chromobox protein homolog 7 (CBX7).	[1]

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 Chromobox protein homolog 7 (CBX7).	[16]

References

• [1] 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.
• [2] 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.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [10] 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.
• [11] 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.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] Resveratrol inhibits oral squamous cell carcinoma cells proliferation while promoting apoptosis through inhibition of CBX7 protein. Environ Toxicol. 2020 Nov;35(11):1234-1240. doi: 10.1002/tox.22988. Epub 2020 Jul 4.
• [15] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [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.