Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNZY74B)

• DOT Name: Growth/differentiation factor 7 (GDF7)
• Synonyms: GDF-7
• Gene Name: GDF7
• Related Disease:
  Alzheimer disease
  Alzheimer disease 3
  Atrial fibrillation
  Barrett esophagus
  Esophageal adenocarcinoma
  Familial multiple trichoepithelioma
  Prostate carcinoma
  Tendinopathy
• UniProt ID: GDF7_HUMAN
• Pfam ID: PF00019 ; PF00688
• Sequence:
  MDLSAAAALCLWLLSACRPRDGLEAAAVLRAAGAGPVRSPGGGGGGGGGGRTLAQAAGAA
  AVPAAAVPRARAARRAAGSGFRNGSVVPHHFMMSLYRSLAGRAPAGAAAVSASGHGRADT
  ITGFTDQATQDESAAETGQSFLFDVSSLNDADEVVGAELRVLRRGSPESGPGSWTSPPLL
  LLSTCPGAARAPRLLYSRAAEPLVGQRWEAFDVADAMRRHRREPRPPRAFCLLLRAVAGP
  VPSPLALRRLGFGWPGGGGSAAEERAVLVVSSRTQRKESLFREIRAQARALGAALASEPL
  PDPGTGTASPRAVIGGRRRRRTALAGTRTAQGSGGGAGRGHGRRGRSRCSRKPLHVDFKE
  LGWDDWIIAPLDYEAYHCEGLCDFPLRSHLEPTNHAIIQTLLNSMAPDAAPASCCVPARL
  SPISILYIDAANNVVYKQYEDMVVEACGCR
• Function: May play an active role in the motor area of the primate neocortex.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  TGF-beta sig.ling pathway (hsa04350)
  Axon guidance (hsa04360)
  Hippo sig.ling pathway (hsa04390)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Alzheimer disease 3	DISVT69G	Strong	Biomarker	[1]
Atrial fibrillation	DIS15W6U	Strong	Altered Expression	[2]
Barrett esophagus	DIS416Y7	Strong	Genetic Variation	[3]
Esophageal adenocarcinoma	DISODWFP	Strong	Genetic Variation	[3]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Genetic Variation	[3]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[4]
Tendinopathy	DISJH7UX	Strong	Biomarker	[5]

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 Growth/differentiation factor 7 (GDF7).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Growth/differentiation factor 7 (GDF7).	[10]

3 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 Growth/differentiation factor 7 (GDF7).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Growth/differentiation factor 7 (GDF7).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Growth/differentiation factor 7 (GDF7).	[9]

References

• [1] Synergistic promoting effects of bone morphogenetic protein 12/connective tissue growth factor on functional differentiation of tendon derived stem cells and patellar tendon window defect regeneration.J Biomech. 2018 Jan 3;66:95-102. doi: 10.1016/j.jbiomech.2017.11.004. Epub 2017 Nov 7.
• [2] Genome-wide profiling reveals atrial fibrillation-related circular RNAs in atrial appendages.Gene. 2020 Feb 20;728:144286. doi: 10.1016/j.gene.2019.144286. Epub 2019 Dec 12.
• [3] The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk.Cancer Med. 2016 May;5(5):888-91. doi: 10.1002/cam4.641. Epub 2016 Jan 18.
• [4] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [5] Aspirin promotes tenogenic differentiation of tendon stem cells and facilitates tendinopathy healing through regulating the GDF7/Smad1/5 signaling pathway.J Cell Physiol. 2020 May;235(5):4778-4789. doi: 10.1002/jcp.29355. Epub 2019 Oct 21.
• [6] 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.
• [7] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.