P2RY1

P2Y purinoreceptor 1

Score: 0.730 Price: $0.73 Low Druggability Status: active Wiki: P2RY1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

402

DEBATES

3D Protein Structure

🧬 P2RY1 — PDB 4XNV Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.41

Clinical Stage

Phase I

Target Class

Gpcr

Safety

0.60

Druggability Analysis

Drug Development0.15

Structural Tractability0.70

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Preclinical

Therapeutic Areas:

Platelet aggregation disorders and thrombosis Neurodegenerative diseases (Alzheimer's, Parkinson's) Neuroinflammation and neuroimmunology Stroke and ischemic injury Pain and neuroprotection

Druggability Rationale: P2Y1 exhibits high druggability (0.80 score) as a validated GPCR target with well-characterized orthosteric binding pockets demonstrated across 5 PDB structures at 2.2 Å resolution, established chemical matter (MRS2500), and precedent for purinergic receptor modulation. The availability of cryo-EM structures and AlphaFold models further supports rational drug design approaches for both antagonists and agonists.

Mechanism: GPCR antagonists or agonists modulating purinergic signaling

Drug Pipeline (1 compounds)

1 Preclinical

Known Drugs:

MRS2500 (investigational) — research tool

Structural Data:

PDB (5) ✓AlphaFold ✓Cryo-EM ✓

4XNV 4XNW 7XXH 8WJX 9JCL

UniProt: P47900

Binding Pocket Analysis:

The orthosteric binding pocket accommodates ADP and nucleotide analogs, characterized by conserved arginine and aspartate residues for nucleotide recognition typical of purinergic receptors. Structural data (PDB: 4XNV, 4XNW) reveal both agonist and antagonist binding modes, with allosteric modulation sites potentially accessible for selective ligand design.

🧬 3D Protein Structure

🧬 P2RY1 — PDB 4XNV Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

P2Y1 selectivity faces challenges due to structural homology with other adenine nucleotide-binding P2Y receptors (P2Y12, P2Y13), requiring ligand optimization to minimize off-target platelet effects while achieving CNS penetration for neuroprotection. Selectivity advantages exist through orthosteric pocket residue differences compared to P2Y12, enabling isoform-selective antagonists.