P2RY12

P2Y purinoreceptor 12

Score: 0.594 Price: $0.59 Medium Druggability Status: active Wiki: P2RY12

🔥 Neuroinflammation 🧠 Neurodegeneration

HYPOTHESES

6

PAPERS

44

KG EDGES

251

DEBATES

1

3D Protein Structure

🧬 P2RY12 — PDB 4NTJ Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.55

Clinical Stage

Approved

Target Class

Gpcr

Safety

0.50

Druggability Analysis

Drug Development1.00

Structural Tractability0.70

Target Class0.85

Safety Profile0.50

Key Metrics

PDB Structures:

5

Known Drugs:

3

Approved:

3

In Clinical Trials:

0

Drug Pipeline (3 compounds)

3 Approved

Druggability Rationale: P2RY12 is highly druggable due to its well-characterized orthosteric binding pocket, validated by 5 crystal structures at 2.5 Å resolution and multiple FDA-approved antagonists (clopidogrel, ticagrelor, prasugrel) demonstrating clinical efficacy. As a GPCR with established structure-activity relationships and a 0.90 druggability score, it presents an accessible target for rational drug design with clear precedent for small-molecule antagonism.

Mechanism: P2Y12 receptor antagonists blocking ADP-mediated signaling

Drug Pipeline (3 compounds)

3 Approved

Known Drugs:

Clopidogrel (approved) — antiplatelet therapy

Ticagrelor (approved) — antiplatelet therapy

Prasugrel (approved) — antiplatelet therapy

Structural Data:

PDB (5) ✓AlphaFold ✓Cryo-EM ✓

4NTJ 4PXZ 4PY0 7PP1 7XXI

UniProt: Q9H244

🧬 3D Protein Structure

🧬 P2RY12 — PDB 4NTJ Click to expand interactive 3D viewer

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

P2Y12 selectivity from other purinergic receptors (P2Y1, P2Y13) is critical to avoid off-target effects; existing approved drugs show good selectivity but bleeding risk remains a potential safety liability when targeting P2Y12 on platelets versus microglia. Tissue-selective delivery or isoform-specific modulation could help mitigate systemic antiplatelet complications.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (8)

Relevant trials from ClinicalTrials.gov

Active

3

Completed

5

Total Enrollment

8,042

By Phase

NA: 2 · PHASE3: 1 · PHASE4: 4 · Unknown: 1

Imapct of bioMarkers on Pharmacodynamics and Bleeding Risk of Direct Oral AntiCoagulants and Ticagrelor Study II Not Yet Recruiting

Unknown NCT05764356 n=2000

Novel Oral Anticoagulants, NOACs, Rivaroxaban

Interventions: Detection of genotype and RNA profile in, Indicators test related to coagulation f, Indicators test related to platelet func

Sponsor: Peking University First Hospital | Started: 2023-03

Acetyl Salicylic Elimination Trial JAPAN: The ASET JAPAN Pilot Study Active Not Recruiting

NA NCT05117866 n=307

Chronic Coronary Syndrome, Non ST Segment Elevation Acute Coronary

Interventions: prasugrel Monotherapy

Sponsor: Meditrix Corp | Started: 2020-09-15

The Nordic Aortic Valve Intervention Trial 4 (NOTION-4) Active Not Recruiting

NA NCT06449469 n=352

Aortic Valve Stenosis, Cardiovascular Diseases, Heart Diseases

Interventions: Rivaroxaban, Acetylsalicylic acid, Clopidogrel

Sponsor: Rigshospitalet, Denmark | Started: 2021-05-01

P3AMI Antiplatelet Trial Completed

PHASE4 NCT02376283 n=87

Heart Attack

Interventions: Prasugrel, Clopidogrel, ticagrelor

Sponsor: The Royal Wolverhampton Hospitals NHS Trust | Started: 2015-03-09

Cangrelor Following Ticagrelor Loading vs Ticagrelor Loading Alone in STEMI Completed

PHASE4 NCT02943369 n=30

STEMI

Interventions: Ticagrelor 180 mg loading dose, Cangrelor 30 mcg/kg bolus + 4 mcg/kg/min

Sponsor: Attikon Hospital | Started: 2017-07-28

EDUCATE: The MEDTRONIC Endeavor Drug Eluting Stenting: Understanding Care, Antiplatelet Agents and Thrombotic Events Completed

PHASE4 NCT01069003 n=2272

Coronary Artery Disease

Interventions: Placebo Arm, Thienopyridine Therapy, Surveillance Arm

Sponsor: Medtronic Vascular | Started: 2010-04

XIENCE V® USA Dual Antiplatelet Therapy (DAPT) Cohort Completed

PHASE4 NCT01106534 n=870

Chronic Total Occlusion of Coronary Arte, Vascular Disease, Myocardial Ischemia

Interventions: placebo + aspirin, clopidogrel + aspirin OR prasugrel + asp, XIENCE V Everolimus Eluting Coronary Ste

Sponsor: Abbott Medical Devices | Started: 2009-08

A Study Exploring Two Strategies of Rivaroxaban (JNJ39039039; BAY-59-7939) and One of Oral Vitamin K Antagonist in Patie Completed

PHASE3 NCT01830543 n=2124

Atrial Fibrillation, Percutaneous Coronary Intervention

Interventions: rivaroxaban 2.5 mg, rivaroxaban 15 mg, rivaroxaban 10 mg

Sponsor: Janssen Scientific Affairs, LLC | Started: 2013-05-10

Linked Hypotheses (8)

Purinergic P2Y12 Inverse Agonist Therapy0.703

Microglial Purinergic Reprogramming0.701

P2RY12-mediated autophagy inhibition in cerebral VSMCs impairs CAA clearance0.605

P2RY12-driven autophagy impairment in cerebral VSMCs mediates BBB breakdown and neurovascular unit d0.585

Pharmacological P2RY12 inhibition (ticagrelor/clopidogrel) as repurposing probe for neurovascular ou0.583

Female Microglia Exhibit Reduced P2Y12 Expression Conferring Neuroprotection Through Attenuated Chem0.580

Cerebral VSMC foam cells induce pericyte detachment via PDGF-BB/VEGF imbalance, impairing neurovascu0.473

P2RY12 activation induces cellular senescence in cerebral VSMCs, driving neurodegeneration via SASP 0.373

Linked Experiments (3)

P2RY12 inhibition in atherosclerosis mouse model0.900

VSMC cholesterol efflux and P2RY12 signaling0.900

In vivo autophagy modulation in atherosclerotic mice0.850

Scoring Dimensions

Knowledge Graph (20)

associated with (1)

P2RY12→neurodegeneration

biomarker for (1)

co discussed (13)

NTN1→P2RY12HSPG2→P2RY12P2RY12→P2RX7P2RY12→AQP4P2RY12→EPHB4

▸ Show 8 more

P2RY12→SMPD1P2RY12→C1QAP2RY12→CERS2HK2→P2RY12TREM2→P2RY12P2RY12→C1QP2RY12→CX3CR1P2RY12→ANXA1

expressed in (2)

TMEM119→P2RY12P2RY12→TREM2

inhibits (3)

ACTB→P2RY12P2RY12→APOA1P2RY12→ULK1

Debate History (1)

Should P2RY12 (P2Y purinoreceptor 12) be prioritized as a therapeutic target for2026-04-21