Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX2W0WD)

• DOT Name: P2Y purinoceptor 12 (P2RY12)
• Synonyms: P2Y12; ADP-glucose receptor; ADPG-R; P2T(AC); P2Y(AC); P2Y(cyc); P2Y12 platelet ADP receptor; P2Y(ADP); SP1999
• Gene Name: P2RY12
• Related Disease: Platelet-type bleeding disorder 8
• UniProt ID: P2Y12_HUMAN
• PDB ID: 4NTJ; 4PXZ; 4PY0; 7PP1; 7XXI
• Pfam ID: PF00001
• Sequence:
  MQAVDNLTSAPGNTSLCTRDYKITQVLFPLLYTVLFFVGLITNGLAMRIFFQIRSKSNFI
  IFLKNTVISDLLMILTFPFKILSDAKLGTGPLRTFVCQVTSVIFYFTMYISISFLGLITI
  DRYQKTTRPFKTSNPKNLLGAKILSVVIWAFMFLLSLPNMILTNRQPRDKNVKKCSFLKS
  EFGLVWHEIVNYICQVIFWINFLIVIVCYTLITKELYRSYVRTRGVGKVPRKKVNVKVFI
  IIAVFFICFVPFHFARIPYTLSQTRDVFDCTAENTLFYVKESTLWLTSLNACLDPFIYFF
  LCKSFRNSLISMLKCPNSATSLSQDNRKKEQDGGDPNEETPM
• Function: Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.
• Tissue Specificity: Highly expressed in the platelets, lower levels in the brain. Lowest levels in the lung, appendix, pituitary and adrenal gland. Expressed in the spinal cord and in the fetal brain.
• KEGG Pathway:
  Efferocytosis (hsa04148)
  Platelet activation (hsa04611)
• Reactome Pathway:
  P2Y receptors (R-HSA-417957)
  G alpha (i) signalling events (R-HSA-418594)
  ADP signalling through P2Y purinoceptor 12 (R-HSA-392170)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Platelet-type bleeding disorder 8	DISMMCRF	Strong	Autosomal recessive	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Clopidogrel	DMOL54H	Approved	P2Y purinoceptor 12 (P2RY12) affects the response to substance of Clopidogrel.	[4]
adenosine diphosphate	DMFUHKP	Investigative	P2Y purinoceptor 12 (P2RY12) affects the response to substance of adenosine diphosphate.	[5]

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 P2Y purinoceptor 12 (P2RY12).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
ANTHRAQUINONE	DM29I0Y	Investigative	ANTHRAQUINONE decreases the activity of P2Y purinoceptor 12 (P2RY12).	[3]

References

• [1] Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1978-83. doi: 10.1073/pnas.0437879100. Epub 2003 Feb 10.
• [2] 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.
• [3] ATP and ADP enhance DNA damage repair in -irradiated BEAS-2B human bronchial epithelial cells through activation of P2X7 and P2Y12 receptors. Toxicol Appl Pharmacol. 2020 Nov 15;407:115240. doi: 10.1016/j.taap.2020.115240. Epub 2020 Sep 14.
• [4] Platelet reactivity and clopidogrel resistance are associated with the H2 haplotype of the P2Y12-ADP receptor gene. Int J Cardiol. 2009 Apr 17;133(3):341-5. doi: 10.1016/j.ijcard.2007.12.118. Epub 2008 May 15.
• [5] Effect of P2Y1 and P2Y12 genetic polymorphisms on the ADP-induced platelet aggregation in a Korean population. Thromb Res. 2013 Aug;132(2):221-6. doi: 10.1016/j.thromres.2013.06.020. Epub 2013 Jul 10.