Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX5VURU)

• DOT Name: Protein GPR107 (GPR107)
• Synonyms: Lung seven transmembrane receptor 1
• Gene Name: GPR107
• Related Disease:
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
• UniProt ID: GP107_HUMAN
• Pfam ID: PF06814
• Sequence:
  MAALAPVGSPASRGPRLAAGLRLLPMLGLLQLLAEPGLGRVHHLALKDDVRHKVHLNTFG
  FFKDGYMVVNVSSLSLNEPEDKDVTIGFSLDRTKNDGFSSYLDEDVNYCILKKQSVSVTL
  LILDISRSEVRVKSPPEAGTQLPKIIFSRDEKVLGQSQEPNVNPASAGNQTQKTQDGGKS
  KRSTVDSKAMGEKSFSVHNNGGAVSFQFFFNISTDDQEGLYSLYFHKCLGKELPSDKFTF
  SLDIEITEKNPDSYLSAGEIPLPKLYISMAFFFFLSGTIWIHILRKRRNDVFKIHWLMAA
  LPFTKSLSLVFHAIDYHYISSQGFPIEGWAVVYYITHLLKGALLFITIALIGTGWAFIKH
  ILSDKDKKIFMIVIPLQVLANVAYIIIESTEEGTTEYGLWKDSLFLVDLLCCGAILFPVV
  WSIRHLQEASATDGKGDSMGPLQQRANLRAGSRIESHHFAQADLELLASSCPPASVSQRA
  GITAAINLAKLKLFRHYYVLIVCYIYFTRIIAFLLKLAVPFQWKWLYQLLDETATLVFFV
  LTGYKFRPASDNPYLQLSQEEEDLEMESVVTTSGVMESMKKVKKVTNGSVEPQGEWEGAV
• Function: Has been proposed to act as a receptor for neuronostatin, a peptide derived from the somatostatin/SST precursor. Involved in blood sugar regulation through the induction of glucagon in response to low glucose; (Microbial infection) Required for intoxication by Pseudomonas aeruginosa exotoxin A and Campylobacter jejuni CDT. May contribute to the retrograde transport of bacterial toxins, including cholera toxin, from the trans-Golgi network to the endoplasmic reticulum.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[1]
Liver cancer	DISDE4BI	Limited	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Protein GPR107 (GPR107).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein GPR107 (GPR107).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein GPR107 (GPR107).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein GPR107 (GPR107).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein GPR107 (GPR107).	[6]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Protein GPR107 (GPR107).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Protein GPR107 (GPR107).	[6]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Protein GPR107 (GPR107).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein GPR107 (GPR107).	[9]

References

• [1] LncGPR107 drives the self-renewal of liver tumor initiating cells and liver tumorigenesis through GPR107-dependent manner.J Exp Clin Cancer Res. 2018 Jun 20;37(1):121. doi: 10.1186/s13046-018-0794-3.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [8] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [9] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.