Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2L4XZX)

• DOT Name: Chromobox protein homolog 1 (CBX1)
• Synonyms: HP1Hsbeta; Heterochromatin protein 1 homolog beta; HP1 beta; Heterochromatin protein p25; M31; Modifier 1 protein; p25beta
• Gene Name: CBX1
• Related Disease:
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
  Myeloid leukaemia
  Neoplasm
  Prostate neoplasm
  Retinoblastoma
  Thyroid gland carcinoma
  Thyroid tumor
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: CBX1_HUMAN
• PDB ID: 2FMM; 3F2U; 3Q6S; 5T1G; 6D07; 6D08
• Pfam ID: PF00385 ; PF01393
• Sequence:
  MGKKQNKKKVEEVLEEEEEEYVVEKVLDRRVVKGKVEYLLKWKGFSDEDNTWEPEENLDC
  PDLIAEFLQSQKTAHETDKSEGGKRKADSDSEDKGEESKPKKKKEESEKPRGFARGLEPE
  RIIGATDSSGELMFLMKWKNSDEADLVPAKEANVKCPQVVISFYEERLTWHSYPSEDDDK
  KDDKN
• Function: Component of heterochromatin. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. Interaction with lamin B receptor (LBR) can contribute to the association of the heterochromatin with the inner nuclear membrane.
• Tissue Specificity: Expressed in all adult and embryonic tissues.
• Reactome Pathway: HCMV Early Events (R-HSA-9609690)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[2]
Myeloid leukaemia	DISMN944	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[6]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[7]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[8]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	moderate	Biomarker	[9]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[9]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[10]
Prostate cancer	DISF190Y	Limited	Biomarker	[11]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Chromobox protein homolog 1 (CBX1) affects the response to substance of Fluorouracil.	[24]

10 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Chromobox protein homolog 1 (CBX1).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Chromobox protein homolog 1 (CBX1).	[13]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Chromobox protein homolog 1 (CBX1).	[14]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Chromobox protein homolog 1 (CBX1).	[15]
Marinol	DM70IK5	Approved	Marinol increases the expression of Chromobox protein homolog 1 (CBX1).	[16]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Chromobox protein homolog 1 (CBX1).	[17]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Chromobox protein homolog 1 (CBX1).	[18]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Chromobox protein homolog 1 (CBX1).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Chromobox protein homolog 1 (CBX1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Chromobox protein homolog 1 (CBX1).	[23]

3 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 affects the methylation of Chromobox protein homolog 1 (CBX1).	[19]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Chromobox protein homolog 1 (CBX1).	[20]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Chromobox protein homolog 1 (CBX1).	[22]

References

• [1] CBX8 Suppresses Tumor Metastasis via Repressing Snail in Esophageal Squamous Cell Carcinoma.Theranostics. 2017 Aug 15;7(14):3478-3488. doi: 10.7150/thno.20717. eCollection 2017.
• [2] HP1 suppresses metastasis of human cancer cells by decreasing the expression and activation of MMP2.Int J Oncol. 2014 Dec;45(6):2541-8. doi: 10.3892/ijo.2014.2646. Epub 2014 Sep 9.
• [3] Transcriptional expressions of Chromobox 1/2/3/6/8 as independent indicators for survivals in hepatocellular carcinoma patients.Aging (Albany NY). 2018 Nov 27;10(11):3450-3473. doi: 10.18632/aging.101658.
• [4] Granulocyte maturation determines ability to release chromatin NETs and loss of DNA damage response; these properties are absent in immature AML granulocytes.Biochim Biophys Acta. 2013 Mar;1833(3):767-79. doi: 10.1016/j.bbamcr.2012.12.012. Epub 2012 Dec 23.
• [5] CBX4 exhibits oncogenic activities in breast cancer via Notch1 signaling.Int J Biochem Cell Biol. 2018 Feb;95:1-8. doi: 10.1016/j.biocel.2017.12.006. Epub 2017 Dec 8.
• [6] Global analysis of differentially expressed genes in androgen-independent prostate cancer.Prostate Cancer Prostatic Dis. 2007;10(2):167-74. doi: 10.1038/sj.pcan.4500933. Epub 2007 Jan 2.
• [7] Dynamic assembly of chromatin complexes during cellular senescence: implications for the growth arrest of human melanocytic nevi.Aging Cell. 2007 Aug;6(4):577-91. doi: 10.1111/j.1474-9726.2007.00308.x. Epub 2007 Jun 18.
• [8] Heterochromatin protein 1 expression is reduced in human thyroid malignancy.Lab Invest. 2014 Jul;94(7):788-95. doi: 10.1038/labinvest.2014.68. Epub 2014 May 19.
• [9] Chromobox homolog 2 protein: A novel biomarker for predicting prognosis and Taxol sensitivity in patients with breast cancer.Oncol Lett. 2017 Mar;13(3):1149-1156. doi: 10.3892/ol.2016.5529. Epub 2016 Dec 23.
• [10] Prognostic values of distinct CBX family members in breast cancer.Oncotarget. 2017 Sep 28;8(54):92375-92387. doi: 10.18632/oncotarget.21325. eCollection 2017 Nov 3.
• [11] Human heterochromatin protein 1 isoforms regulate androgen receptor signaling in prostate cancer.J Mol Endocrinol. 2013 Apr 23;50(3):401-9. doi: 10.1530/JME-13-0024. Print 2013 Jun.
• [12] 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.
• [13] 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.
• [14] Expression profiling of the estrogen responsive genes in response to phytoestrogens using a customized DNA microarray. FEBS Lett. 2005 Mar 14;579(7):1732-40.
• [15] 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.
• [16] Genomic and proteomic analysis of the effects of cannabinoids on normal human astrocytes. Brain Res. 2008 Jan 29;1191:1-11.
• [17] Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
• [18] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [19] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [20] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [21] 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.
• [22] 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.
• [23] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [24] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.