Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI7Q2JW)

• DOT Name: CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7)
• Synonyms: Chemokine-like factor superfamily member 7
• Gene Name: CMTM7
• Related Disease:
  Neoplasm
  Cardiac failure
  Non-small-cell lung cancer
  Carcinoma of liver and intrahepatic biliary tract
  Cervical cancer
  Liver cancer
  Metastatic malignant neoplasm
  Gastric cancer
  Stomach cancer
• UniProt ID: CKLF7_HUMAN
• Pfam ID: PF01284
• Sequence:
  MSHGAGLVRTTCSSGSALGPGAGAAQPSASPLEGLLDLSYPRTHAALLKVAQMVTLLIAF
  ICVRSSLWTNYSAYSYFEVVTICDLIMILAFYLVHLFRFYRVLTCISWPLSELLHYLIGT
  LLLLIASIVAASKSYNQSGLVAGAIFGFMATFLCMASIWLSYKISCVTQSTDAAV
• Tissue Specificity: Highly expressed in leukocytes.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]
Cardiac failure	DISDC067	Strong	Genetic Variation	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Disputed	Biomarker	[1]
Cervical cancer	DISFSHPF	Disputed	Altered Expression	[1]
Liver cancer	DISDE4BI	Disputed	Biomarker	[1]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Altered Expression	[1]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[4]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[4]

13 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 7 (CMTM7).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[9]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[5]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of CKLF-like MARVEL transmembrane domain-containing protein 7 (CMTM7).	[12]

References

• [1] Overexpression of CMTM7 inhibits cell growth and migration in liver cancer.Kaohsiung J Med Sci. 2019 Jun;35(6):332-340. doi: 10.1002/kjm2.12058. Epub 2019 Mar 23.
• [2] Genomic variation associated with mortality among adults of European and African ancestry with heart failure: the cohorts for heart and aging research in genomic epidemiology consortium.Circ Cardiovasc Genet. 2010 Jun;3(3):248-55. doi: 10.1161/CIRCGENETICS.109.895995. Epub 2010 Apr 17.
• [3] CMTM7 knockdown increases tumorigenicity of human non-small cell lung cancer cells and EGFR-AKT signaling by reducing Rab5 activation.Oncotarget. 2015 Dec 1;6(38):41092-107. doi: 10.18632/oncotarget.5732.
• [4] SOX10-dependent CMTM7 expression inhibits cell proliferation and tumor growth in gastric carcinoma.Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):91-99. doi: 10.1016/j.bbrc.2018.10.172. Epub 2018 Nov 2.
• [5] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [15] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [16] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.