Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMS7NDP)

• DOT Name: CKLF-like MARVEL transmembrane domain-containing protein 5 (CMTM5)
• Synonyms: Chemokine-like factor superfamily member 5
• Gene Name: CMTM5
• Related Disease:
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Myeloid leukaemia
  Neoplasm
  Pancreatic cancer
  Cervical carcinoma
  Squamous cell carcinoma
  Advanced cancer
  Clear cell renal carcinoma
  Coronary atherosclerosis
  Coronary heart disease
  Renal cell carcinoma
• UniProt ID: CKLF5_HUMAN
• Pfam ID: PF01284
• Sequence:
  MLSARDRRDRHPEEGVVAELQGFAVDKAFLTSHKGILLETELALTLIIFICFTASISAYM
  AAALLEFFITLAFLFLYATQYYQRFDRINWPCLLQGHGQSGGPHPLDLLSHSAKVQPQPW
  PGLTPPGWHTPAAVPWVPAPAPGFWSWLLWFICFHSLGSSDFLRCVSAIIIFLVVSFAAV
  TSRDGAAIAAFVFGIILVSIFAYDAFKIYRTEMAPGASQGDQQ
• Tissue Specificity: Highly expressed in the brain.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
leukaemia	DISS7D1V	Strong	Biomarker	[2]
Leukemia	DISNAKFL	Strong	Biomarker	[2]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Pancreatic cancer	DISJC981	Strong	Biomarker	[4]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[5]
Squamous cell carcinoma	DISQVIFL	moderate	Posttranslational Modification	[6]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[7]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[7]
Coronary atherosclerosis	DISKNDYU	Limited	Biomarker	[8]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[8]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[7]

5 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 CKLF-like MARVEL transmembrane domain-containing protein 5 (CMTM5).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 5 (CMTM5).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of CKLF-like MARVEL transmembrane domain-containing protein 5 (CMTM5).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of CKLF-like MARVEL transmembrane domain-containing protein 5 (CMTM5).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of CKLF-like MARVEL transmembrane domain-containing protein 5 (CMTM5).	[13]

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 CKLF-like MARVEL transmembrane domain-containing protein 5 (CMTM5).	[14]

References

• [1] Up-regulation of miR-10b-3p promotes the progression of hepatocellular carcinoma cells via targeting CMTM5.J Cell Mol Med. 2018 Jul;22(7):3434-3441. doi: 10.1111/jcmm.13620. Epub 2018 Apr 24.
• [2] Aberrant expression of CKLF-like MARVEL transmembrane member 5 (CMTM5) by promoter methylation in myeloid leukemia.Leuk Res. 2011 Jun;35(6):771-6. doi: 10.1016/j.leukres.2010.11.023. Epub 2010 Dec 18.
• [3] CMTM5 is downregulated and suppresses tumour growth in hepatocellular carcinoma through regulating PI3K-AKT signalling.Cancer Cell Int. 2017 Nov 29;17:113. doi: 10.1186/s12935-017-0485-8. eCollection 2017.
• [4] CMTM5 induces apoptosis of pancreatic cancer cells and has synergistic effects with TNF-alpha.Biochem Biophys Res Commun. 2009 Sep 11;387(1):139-42. doi: 10.1016/j.bbrc.2009.06.148. Epub 2009 Jul 3.
• [5] CMTM5-v1 induces apoptosis in cervical carcinoma cells.Biochem Biophys Res Commun. 2009 Feb 20;379(4):866-71. doi: 10.1016/j.bbrc.2008.12.126. Epub 2009 Jan 3.
• [6] CMTM5 exhibits tumor suppressor activity through promoter methylation in oral squamous cell carcinoma.Biochem Biophys Res Commun. 2014 May 2;447(2):304-10. doi: 10.1016/j.bbrc.2014.03.158. Epub 2014 Apr 8.
• [7] CMTM5 inhibits renal cancer cell growth through inducing cell-cycle arrest and apoptosis.Oncol Lett. 2017 Aug;14(2):1536-1542. doi: 10.3892/ol.2017.6350. Epub 2017 Jun 8.
• [8] Validation of aspirin response-related transcripts in patients with coronary artery disease and preliminary investigation on CMTM5 function.Gene. 2017 Aug 15;624:56-65. doi: 10.1016/j.gene.2017.04.041. Epub 2017 Apr 28.
• [9] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [10] 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.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] 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.
• [13] 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.
• [14] 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.