Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE72F4O)

• DOT Name: Centriole, cilia and spindle-associated protein (CCSAP)
• Gene Name: CCSAP
• UniProt ID: CCSAP_HUMAN
• Pfam ID: PF15748
• Sequence:
  MSPGSGVKSEYMKRYQEPRWEEYGPCYRELLHYRLGRRLLEQAHAPWLWDDWGPAGSSED
  SASSESSGAGGPAPRCAPPSPPPPVEPATQEEAERRARGAPEEQDAEAGDAEAEDAEDAA
  LPALPVKDVEDKPEQQTRTRETDKSPTSTEPRQQPSALFARGNRKAVKSPQRSSSKIKEN
  KHPFALYGWGEKQTDTGSQKTHNVCASAPVHEIHESALRAKNRRQVEKRKLVAQRQRAHS
  VDVEKNRKMKASSSENPWMTEYMRCYSARA
• Function: Plays a role in microtubule (MT) stabilization and this stabilization involves the maintenance of NUMA1 at the spindle poles. Colocalizes with polyglutamylated MTs to promote MT stabilization and regulate bipolar spindle formation in mitosis. Binding of CCSAP to centrosomes and the spindle around centrosomes during mitosis inhibits MT depolymerization, thereby stabilizing the mitotic spindle. May play a role in embryonic development. May be required for proper cilia beating.

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 Centriole, cilia and spindle-associated protein (CCSAP).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[11]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[14]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Centriole, cilia and spindle-associated protein (CCSAP).	[15]

2 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 decreases the methylation of Centriole, cilia and spindle-associated protein (CCSAP).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Centriole, cilia and spindle-associated protein (CCSAP).	[13]

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] 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.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [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] 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] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [13] 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.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] 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.