Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7VNPQ0)

• DOT Name: P2Y purinoceptor 6 (P2RY6)
• Synonyms: P2Y6
• Gene Name: P2RY6
• UniProt ID: P2RY6_HUMAN
• Pfam ID: PF00001
• Sequence:
  MEWDNGTGQALGLPPTTCVYRENFKQLLLPPVYSAVLAAGLPLNICVITQICTSRRALTR
  TAVYTLNLALADLLYACSLPLLIYNYAQGDHWPFGDFACRLVRFLFYANLHGSILFLTCI
  SFQRYLGICHPLAPWHKRGGRRAAWLVCVAVWLAVTTQCLPTAIFAATGIQRNRTVCYDL
  SPPALATHYMPYGMALTVIGFLLPFAALLACYCLLACRLCRQDGPAEPVAQERRGKAARM
  AVVVAAAFAISFLPFHITKTAYLAVRSTPGVPCTVLEAFAAAYKGTRPFASANSVLDPIL
  FYFTQKKFRRRPHELLQKLTAKWQRQGR
• Function: Receptor for extracellular UDP > UTP > ATP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Efferocytosis (hsa04148)
• Reactome Pathway:
  P2Y receptors (R-HSA-417957)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of P2Y purinoceptor 6 (P2RY6).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of P2Y purinoceptor 6 (P2RY6).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of P2Y purinoceptor 6 (P2RY6).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of P2Y purinoceptor 6 (P2RY6).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of P2Y purinoceptor 6 (P2RY6).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of P2Y purinoceptor 6 (P2RY6).	[6]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of P2Y purinoceptor 6 (P2RY6).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of P2Y purinoceptor 6 (P2RY6).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of P2Y purinoceptor 6 (P2RY6).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of P2Y purinoceptor 6 (P2RY6).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of P2Y purinoceptor 6 (P2RY6).	[11]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of P2Y purinoceptor 6 (P2RY6).	[12]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of P2Y purinoceptor 6 (P2RY6).	[13]

References

• [1] 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.
• [2] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1. J Appl Toxicol. 2023 Aug;43(8):1214-1224. doi: 10.1002/jat.4457. Epub 2023 Mar 11.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] Low dose of bisphenol a modulates ovarian cancer gene expression profile and promotes epithelial to mesenchymal transition via canonical Wnt pathway. Toxicol Sci. 2018 Aug 1;164(2):527-538.
• [11] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [12] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [13] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.