Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG28GH2)

• DOT Name: CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8)
• Synonyms: Chemokine-like factor superfamily member 8
• Gene Name: CMTM8
• Related Disease:
  Bladder cancer
  Neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
  Advanced cancer
  Bone osteosarcoma
  Osteosarcoma
  Carcinoma
  Metastatic malignant neoplasm
• UniProt ID: CKLF8_HUMAN
• Pfam ID: PF01284
• Sequence:
  MEEPQRARSHTVTTTASSFAENFSTSSSSFAYDREFLRTLPGFLIVAEIVLGLLVWTLIA
  GTEYFRVPAFGWVMFVAVFYWVLTVFFLIIYITMTYTRIPQVPWTTVGLCFNGSAFVLYL
  SAAVVDASSVSPERDSHNFNSWAASSFFAFLVTICYAGNTYFSFIAWRSRTIQ
• Tissue Specificity: Highly expressed in liver and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[2]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[3]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[3]
Carcinoma	DISH9F1N	Limited	Altered Expression	[4]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[4]

12 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 CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[10]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[16]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[15]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the acetylation of CKLF-like MARVEL transmembrane domain-containing protein 8 (CMTM8).	[18]

References

• [1] Functional characterization of the tumor suppressor CMTM8 and its association with prognosis in bladder cancer.Tumour Biol. 2016 May;37(5):6217-25. doi: 10.1007/s13277-015-4508-6. Epub 2015 Nov 28.
• [2] CMTM8 inhibits the carcinogenesis and progression of bladder cancer.Oncol Rep. 2015 Dec;34(6):2853-63. doi: 10.3892/or.2015.4310.
• [3] Focal chromosomal copy number aberrations identify CMTM8 and GPR177 as new candidate driver genes in osteosarcoma.PLoS One. 2014 Dec 31;9(12):e115835. doi: 10.1371/journal.pone.0115835. eCollection 2014.
• [4] CMTM8 is Frequently Downregulated in Multiple Solid Tumors.Appl Immunohistochem Mol Morphol. 2017 Feb;25(2):122-128. doi: 10.1097/PAI.0000000000000274.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [8] 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.
• [9] 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.
• [10] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [11] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [14] 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.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [18] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.