Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT02OX35)

• DOT Name: Uracil nucleotide/cysteinyl leukotriene receptor (GPR17)
• Synonyms: UDP/CysLT receptor; G-protein coupled receptor 17; P2Y-like receptor; R12
• Gene Name: GPR17
• UniProt ID: GPR17_HUMAN
• PDB ID: 7Y89
• Pfam ID: PF00001
• Sequence:
  MSKRSWWAGSRKPPREMLKLSGSDSSQSMNGLEVAPPGLITNFSLATAEQCGQETPLENM
  LFASFYLLDFILALVGNTLALWLFIRDHKSGTPANVFLMHLAVADLSCVLVLPTRLVYHF
  SGNHWPFGEIACRLTGFLFYLNMYASIYFLTCISADRFLAIVHPVKSLKLRRPLYAHLAC
  AFLWVVVAVAMAPLLVSPQTVQTNHTVVCLQLYREKASHHALVSLAVAFTFPFITTVTCY
  LLIIRSLRQGLRVEKRLKTKAVRMIAIVLAIFLVCFVPYHVNRSVYVLHYRSHGASCATQ
  RILALANRITSCLTSLNGALDPIMYFFVAEKFRHALCNLLCGKRLKGPPPSFEGKTNESS
  LSAKSEL
• Function: Dual specificity receptor for uracil nucleotides and cysteinyl leukotrienes (CysLTs). Signals through G(i) and inhibition of adenylyl cyclase. May mediate brain damage by nucleotides and CysLTs following ischemia.
• Tissue Specificity: Expressed in brain, kidney, heart and umbilical vein endothelial cells. Highest level in brain.
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  P2Y receptors (R-HSA-417957)
  G alpha (i) signalling events (R-HSA-418594)
  Leukotriene receptors (R-HSA-391906)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Uracil nucleotide/cysteinyl leukotriene receptor (GPR17).	[1]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Uracil nucleotide/cysteinyl leukotriene receptor (GPR17).	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Uracil nucleotide/cysteinyl leukotriene receptor (GPR17).	[3]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Uracil nucleotide/cysteinyl leukotriene receptor (GPR17).	[4]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Uracil nucleotide/cysteinyl leukotriene receptor (GPR17).	[2]

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 Uracil nucleotide/cysteinyl leukotriene receptor (GPR17).	[5]

References

• [1] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [2] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [3] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [4] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [5] 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.