Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7P006B)

• DOT Name: Centromere protein L (CENPL)
• Synonyms: CENP-L; Interphase centromere complex protein 33
• Gene Name: CENPL
• UniProt ID: CENPL_HUMAN
• PDB ID: 7PKN; 7QOO; 7R5S; 7R5V; 7XHN; 7XHO; 7YWX; 7YYH
• Pfam ID: PF13092
• Sequence:
  MDSYSAPESTPSASSRPEDYFIGATPLQKRLESVRKQSSFILTPPRRKIPQCSQLQEDVD
  PQKVAFLLHKQWTLYSLTPLYKFSYSNLKEYSRLLNAFIVAEKQKGLAVEVGEDFNIKVI
  FSTLLGMKGTQRDPEAFLVQIVSKSQLPSENREGKVLWTGWFCCVFGDSLLETVSEDFTC
  LPLFLANGAESNTAIIGTWFQKTFDCYFSPLAINAFNLSWMAAMWTACKMDHYVATTEFL
  WSVPCSPQSLDISFAIHPEDAKALWDSVHKTPGEVTQEEVDLFMDCLYSHFHRHFKIHLS
  ATRLVRVSTSVASAHTDGKIKILCHKYLIGVLAYLTELAIFQIE
• Function: Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex.
• Reactome Pathway:
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Deposition of new CENPA-containing nucleosomes at the centromere (R-HSA-606279)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)

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 decreases the expression of Centromere protein L (CENPL).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centromere protein L (CENPL).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Centromere protein L (CENPL).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Centromere protein L (CENPL).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Centromere protein L (CENPL).	[4]
Marinol	DM70IK5	Approved	Marinol affects the expression of Centromere protein L (CENPL).	[5]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Centromere protein L (CENPL).	[6]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Centromere protein L (CENPL).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Centromere protein L (CENPL).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Centromere protein L (CENPL).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centromere protein L (CENPL).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Centromere protein L (CENPL).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Centromere protein L (CENPL).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Centromere protein L (CENPL).	[14]

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 Centromere protein L (CENPL).	[9]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] 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.
• [3] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [4] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [5] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [6] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [7] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [8] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [9] 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.
• [10] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [11] 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.
• [12] 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.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.