GPR37

G-protein coupled receptor 37

Score: 0.625 Price: $0.62 Low Druggability Status: active Wiki: GPR37

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

148

DEBATES

3D Protein Structure

🔮 GPR37 — AlphaFold O15354 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.30

Clinical Stage

Approved

Target Class

Gpcr

Safety

0.60

Druggability Analysis

Drug Development0.60

Structural Tractability0.30

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (2 compounds)

2 Preclinical

Therapeutic Areas:

Parkinson's disease Neurodegeneration Neuroprotection Dopaminergic neuron preservation Neurodegenerative disorders

Druggability Rationale: GPR37 presents moderate druggability (0.60 score) as a GPCR with established G-protein coupling mechanisms and validated neuroprotective function, supported by investigational ligands like Prosaposin demonstrating target engagement. However, the lack of crystal structures (0 PDB entries), orphan receptor status with limited endogenous ligand characterization, and absence of cryo-EM data present significant challenges in rational drug design and binding site optimization.

Mechanism: GPR37 agonists or modulators would activate the receptor to promote dopaminergic neuron survival and neuroprotection, counteracting the neurodegeneration characteristic of Parkinson's disease. Ligands binding to GPR37 would enhance G-protein signaling cascades that support neuronal viability and function.

Drug Pipeline (2 compounds)

2 Preclinical

Known Drugs:

Prosaposin (investigational) — Endogenous neuroprotective ligand for GPR37

TX14(A) (preclinical) — Prosaptide, GPR37 agonist peptide

Structural Data:

PDB —AlphaFold ✓Cryo-EM —

UniProt: O15354

Binding Pocket Analysis:

AlphaFold predictions are available for GPR37 (UniProt O15354) and likely model the canonical seven-transmembrane helical bundle typical of GPCRs with an extracellular ligand-binding region; however, without experimental crystal structure validation or cryo-EM data, the precise binding pocket geometry, allosteric sites, and ligand accommodation details remain unconfirmed and require experimental validation through mutagenesis or chemical screening.

🔮 Predicted Protein Structure (AlphaFold)

🔮 GPR37 — AlphaFold O15354 Click to expand interactive 3D viewer

AI-predicted structure from AlphaFold EBI | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Selectivity & Safety Considerations

GPR37 selectivity against other orphan GPCRs and related family members (GPR37L1) represents a key challenge, as sequence homology among GPCRs often leads to off-target activity. The lack of structural templates necessitates empirical selectivity screening, though the neuroprotection-specific phenotype may provide some therapeutic window if peripheral GPCR activation is minimized.