Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO1I9W0)

• DOT Name: Chromobox protein homolog 6 (CBX6)
• Gene Name: CBX6
• Related Disease:
  Neoplasm
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
• UniProt ID: CBX6_HUMAN
• PDB ID: 3GV6; 3I90
• Pfam ID: PF17218 ; PF00385
• Sequence:
  MELSAVGERVFAAESIIKRRIRKGRIEYLVKWKGWAIKYSTWEPEENILDSRLIAAFEQK
  ERERELYGPKKRGPKPKTFLLKARAQAEALRISDVHFSVKPSASASSPKLHSSAAVHRLK
  KDIRRCHRMSRRPLPRPDPQGGSPGLRPPISPFSETVRIINRKVKPREPKRNRIILNLKV
  IDKGAGGGGAGQGAGALARPKVPSRNRVIGKSKKFSESVLRTQIRHMKFGAFALYKPPPA
  PLVAPSPGKAEASAPGPGLLLAAPAAPYDARSSGSSGCPSPTPQSSDPDDTPPKLLPETV
  SPSAPSWREPEVLDLSLPPESAATSKRAPPEVTAAAGPAPPTAPEPAGASSEPEAGDWRP
  EMSPCSNVVVTDVTSNLLTVTIKEFCNPEDFEKVAAGVAGAAGGGGSIGASK
• 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. Possibly contributes to the target selectivity of the PRC1 complex by binding specific regions of chromatin. Recruitment to chromatin might occur in an H3K27me3-independent fashion. May have a PRC1-independent function in embryonic stem cells.
• KEGG Pathway: Polycomb repressive complex (hsa03083)
• Reactome Pathway:
  RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243)
  Regulation of PTEN gene transcription (R-HSA-8943724)
  Oxidative Stress Induced Senescence (R-HSA-2559580)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[1]
Breast cancer	DIS7DPX1	moderate	Biomarker	[1]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[2]

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 Chromobox protein homolog 6 (CBX6).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Chromobox protein homolog 6 (CBX6).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Chromobox protein homolog 6 (CBX6).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Chromobox protein homolog 6 (CBX6).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Chromobox protein homolog 6 (CBX6).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Chromobox protein homolog 6 (CBX6).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Chromobox protein homolog 6 (CBX6).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Chromobox protein homolog 6 (CBX6).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Chromobox protein homolog 6 (CBX6).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Chromobox protein homolog 6 (CBX6).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Chromobox protein homolog 6 (CBX6).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Chromobox protein homolog 6 (CBX6).	[15]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Chromobox protein homolog 6 (CBX6).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Chromobox protein homolog 6 (CBX6).	[12]

References

• [1] CBX6 is negatively regulated by EZH2 and plays a potential tumor suppressor role in breast cancer.Sci Rep. 2019 Jan 17;9(1):197. doi: 10.1038/s41598-018-36560-4.
• [2] CBX6 overexpression contributes to tumor progression and is predictive of a poor prognosis in hepatocellular carcinoma.Oncotarget. 2017 Mar 21;8(12):18872-18884. doi: 10.18632/oncotarget.14770.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [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] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [13] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [16] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.