Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6P9QBG)

• DOT Name: Cardiotrophin-1 (CTF1)
• Synonyms: CT-1
• Gene Name: CTF1
• Related Disease: Dilated cardiomyopathy
• UniProt ID: CTF1_HUMAN
• Sequence:
  MSRREGSLEDPQTDSSVSLLPHLEAKIRQTHSLAHLLTKYAEQLLQEYVQLQGDPFGLPS
  FSPPRLPVAGLSAPAPSHAGLPVHERLRLDAAALAALPPLLDAVCRRQAELNPRAPRLLR
  RLEDAARQARALGAAVEALLAALGAANRGPRAEPPAATASAASATGVFPAKVLGLRVCGL
  YREWLSRTEGDLGQLLPGGSA
• Function: Induces cardiac myocyte hypertrophy in vitro. Binds to and activates the ILST/gp130 receptor.
• Tissue Specificity: Highly expressed in heart, skeletal muscle, prostate and ovary. Lower levels in lung, kidney, pancreas, thymus, testis and small intestine. Little or no expression in brain, placenta, liver, spleen, colon or peripheral blood leukocytes.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  JAK-STAT sig.ling pathway (hsa04630)
• Reactome Pathway: IL-6-type cytokine receptor ligand interactions (R-HSA-6788467)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dilated cardiomyopathy	DISX608J	Limited	Autosomal dominant	[1]

3 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 Cardiotrophin-1 (CTF1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cardiotrophin-1 (CTF1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Cardiotrophin-1 (CTF1).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cardiotrophin-1 (CTF1).	[3]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Cardiotrophin-1 (CTF1).	[5]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Cardiotrophin-1 (CTF1).	[6]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [5] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [6] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [7] 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.