Druggability & Clinical Context
Druggability
Medium
Score: 0.55
Druggability Analysis
Structural Tractability0.70
Key Metrics
PDB Structures:
5
Known Drugs:
3
Approved:
3
In Clinical Trials:
0
Drug Pipeline (3 compounds)
3 Approved
Therapeutic Areas:Antiplatelet therapy / Cardiovascular disease Neuroinflammation / Neurodegeneration Alzheimer's disease Parkinson's disease Multiple sclerosis Stroke neuroprotection Microglial activation disorders
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 ✓
Binding Pocket Analysis:The orthosteric binding pocket is located within the transmembrane helical bundle and accommodates small nucleotide analogs and irreversible antagonists; structural data (PDB: 4NTJ, 4PXZ, 4PY0, 7PP1, 7XXI) reveal conserved interactions with key residues enabling competitive ADP-site antagonism. An allosteric regulatory region may also exist based on diverse chemical scaffolds of approved drugs showing varied binding modes.
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.
Clinical Trials (8)
Relevant trials from ClinicalTrials.gov
By Phase
NA: 2 · PHASE3: 1 · PHASE4: 4 · Unknown: 1
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
NA
NCT05117866
n=307
Chronic Coronary Syndrome, Non ST Segment Elevation Acute Coronary
Interventions: prasugrel Monotherapy
Sponsor: Meditrix Corp | Started: 2020-09-15
NA
NCT06449469
n=352
Aortic Valve Stenosis, Cardiovascular Diseases, Heart Diseases
Interventions: Rivaroxaban, Acetylsalicylic acid, Clopidogrel
Sponsor: Rigshospitalet, Denmark | Started: 2021-05-01
PHASE4
NCT02376283
n=87
Heart Attack
Interventions: Prasugrel, Clopidogrel, ticagrelor
Sponsor: The Royal Wolverhampton Hospitals NHS Trust | Started: 2015-03-09
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
PHASE4
NCT01069003
n=2272
Coronary Artery Disease
Interventions: Placebo Arm, Thienopyridine Therapy, Surveillance Arm
Sponsor: Medtronic Vascular | Started: 2010-04
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
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