Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT8XKGE)

• DOT Name: Cell surface glycoprotein MUC18 (MCAM)
• Synonyms: Cell surface glycoprotein P1H12; Melanoma cell adhesion molecule; Melanoma-associated antigen A32; Melanoma-associated antigen MUC18; S-endo 1 endothelial-associated antigen; CD antigen CD146
• Gene Name: MCAM
• UniProt ID: MUC18_HUMAN
• PDB ID: 6LYN
• Pfam ID: PF08205 ; PF13927 ; PF07686
• Sequence:
  MGLPRLVCAFLLAACCCCPRVAGVPGEAEQPAPELVEVEVGSTALLKCGLSQSQGNLSHV
  DWFSVHKEKRTLIFRVRQGQGQSEPGEYEQRLSLQDRGATLALTQVTPQDERIFLCQGKR
  PRSQEYRIQLRVYKAPEEPNIQVNPLGIPVNSKEPEEVATCVGRNGYPIPQVIWYKNGRP
  LKEEKNRVHIQSSQTVESSGLYTLQSILKAQLVKEDKDAQFYCELNYRLPSGNHMKESRE
  VTVPVFYPTEKVWLEVEPVGMLKEGDRVEIRCLADGNPPPHFSISKQNPSTREAEEETTN
  DNGVLVLEPARKEHSGRYECQGLDLDTMISLLSEPQELLVNYVSDVRVSPAAPERQEGSS
  LTLTCEAESSQDLEFQWLREETGQVLERGPVLQLHDLKREAGGGYRCVASVPSIPGLNRT
  QLVNVAIFGPPWMAFKERKVWVKENMVLNLSCEASGHPRPTISWNVNGTASEQDQDPQRV
  LSTLNVLVTPELLETGVECTASNDLGKNTSILFLELVNLTTLTPDSNTTTGLSTSTASPH
  TRANSTSTERKLPEPESRGVVIVAVIVCILVLAVLGAVLYFLYKKGKLPCRRSGKQEITL
  PPSRKSELVVEVKSDKLPEEMGLLQGSSGDKRAPGDQGEKYIDLRH
• Function: Plays a role in cell adhesion, and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissue. Its expression may allow melanoma cells to interact with cellular elements of the vascular system, thereby enhancing hematogeneous tumor spread. Could be an adhesion molecule active in neural crest cells during embryonic development. Acts as a surface receptor that triggers tyrosine phosphorylation of FYN and PTK2/FAK1, and a transient increase in the intracellular calcium concentration.
• Tissue Specificity: Detected in endothelial cells in vascular tissue throughout the body. May appear at the surface of neural crest cells during their embryonic migration. Appears to be limited to vascular smooth muscle in normal adult tissues. Associated with tumor progression and the development of metastasis in human malignant melanoma. Expressed most strongly on metastatic lesions and advanced primary tumors and is only rarely detected in benign melanocytic nevi and thin primary melanomas with a low probability of metastasis.
• Reactome Pathway:
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RHOD GTPase cycle (R-HSA-9013405)
  RHOG GTPase cycle (R-HSA-9013408)
  RAC3 GTPase cycle (R-HSA-9013423)
  RHOF GTPase cycle (R-HSA-9035034)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Docetaxel	DMDI269	Approved	Cell surface glycoprotein MUC18 (MCAM) decreases the response to substance of Docetaxel.	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cell surface glycoprotein MUC18 (MCAM).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cell surface glycoprotein MUC18 (MCAM).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cell surface glycoprotein MUC18 (MCAM).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cell surface glycoprotein MUC18 (MCAM).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cell surface glycoprotein MUC18 (MCAM).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cell surface glycoprotein MUC18 (MCAM).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cell surface glycoprotein MUC18 (MCAM).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cell surface glycoprotein MUC18 (MCAM).	[11]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[12]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Cell surface glycoprotein MUC18 (MCAM).	[13]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[14]
Haloperidol	DM96SE0	Approved	Haloperidol increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[15]
Sevoflurane	DMC9O43	Approved	Sevoflurane decreases the expression of Cell surface glycoprotein MUC18 (MCAM).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[17]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[18]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[20]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[22]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cell surface glycoprotein MUC18 (MCAM).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Cell surface glycoprotein MUC18 (MCAM).	[24]

References

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• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray. Acta Pharmacol Sin. 2004 Oct;25(10):1327-33.
• [13] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [14] 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.
• [15] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [16] The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence. Cell Biol Toxicol. 2023 Aug;39(4):1561-1575. doi: 10.1007/s10565-022-09747-9. Epub 2022 Aug 12.
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• [19] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [20] 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.
• [21] 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.
• [22] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [23] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [24] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [25] CD146 expression in human breast cancer cell lines induces phenotypic and functional changes observed in Epithelial to Mesenchymal Transition. PLoS One. 2012;7(8):e43752. doi: 10.1371/journal.pone.0043752. Epub 2012 Aug 30.