Details of Drug Off-Target (DOT)

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

• DOT Name: P2Y purinoceptor 8 (P2RY8)
• Synonyms: P2Y8
• Gene Name: P2RY8
• UniProt ID: P2RY8_HUMAN
• Pfam ID: PF00001
• Sequence:
  MQVPNSTGPDNATLQMLRNPAIAVALPVVYSLVAAVSIPGNLFSLWVLCRRMGPRSPSVI
  FMINLSVTDLMLASVLPFQIYYHCNRHHWVFGVLLCNVVTVAFYANMYSSILTMTCISVE
  RFLGVLYPLSSKRWRRRRYAVAACAGTWLLLLTALSPLARTDLTYPVHALGIITCFDVLK
  WTMLPSVAMWAVFLFTIFILLFLIPFVITVACYTATILKLLRTEEAHGREQRRRAVGLAA
  VVLLAFVTCFAPNNFVLLAHIVSRLFYGKSYYHVYKLTLCLSCLNNCLDPFVYYFASREF
  QLRLREYLGCRRVPRDTLDTRRESLFSARTTSVRSEAGAHPEGMEGATRPGLQRQESVF
• Function: Probable receptor for purines coupled to G-proteins.
• Tissue Specificity: Barely detectable in normal blood leukocytes. Weaker expression was seen in heart, kidney and lung. Not detected in brain.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)

Molecular Interaction Atlas (MIA) of This DOT

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 P2Y purinoceptor 8 (P2RY8).	[1]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of P2Y purinoceptor 8 (P2RY8).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of P2Y purinoceptor 8 (P2RY8).	[2]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of P2Y purinoceptor 8 (P2RY8).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of P2Y purinoceptor 8 (P2RY8).	[4]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of P2Y purinoceptor 8 (P2RY8).	[5]

References

• [1] 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.
• [2] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [5] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [6] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.