SNCA

Synuclein alpha

Score: 0.667 Price: $0.67 Medium Druggability Status: active Wiki: SNCA

🟢 Parkinson's Disease 🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

1439

DEBATES

3D Protein Structure

🧬 SNCA — PDB 1XQ8 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.49

Clinical Stage

Phase II

Target Class

Structural Protein

Safety

0.30

Druggability Analysis

Drug Development0.40

Structural Tractability0.95

Target Class0.50

Safety Profile0.30

Key Metrics

PDB Structures:

187

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (2 compounds)

1 Phase II · 1 Phase I

Therapeutic Areas:

Parkinson's disease Lewy body dementia Multiple system atrophy Neurodegeneration Alpha-synucleinopathies

Druggability Rationale: SNCA demonstrates high druggability (0.80 score) despite being an intrinsically disordered protein, supported by 187 PDB structures, cryo-EM data, and active clinical programs (Prasinezumab in Phase 2). The extensive structural characterization and successful immunotherapy approaches validate this target's tractability for both monoclonal antibodies targeting aggregates and small molecules preventing pathological conformational transitions.

Mechanism: Immunotherapy targeting alpha-synuclein aggregates or small molecules preventing aggregation

Drug Pipeline (2 compounds)

1 Phase II · 1 Phase I

Known Drugs:

Prasinezumab (phase_2) — Parkinson's disease

Cinpanemab (phase_1) — Parkinson's disease

Structural Data:

PDB (187) ✓AlphaFold ✓Cryo-EM ✓

10XU 1XQ8 2KKW 2N0A 3Q26+182 more

UniProt: P37840

Binding Pocket Analysis:

Structural data reveals multiple binding surfaces on alpha-synuclein's intrinsically disordered regions involved in self-association and aggregation, with high-resolution structures (1.23 Å best resolution) enabling identification of conformational epitopes for antibodies and allosteric pockets for aggregation inhibitors. Key structural regions include the NAC domain and C-terminal tail, which are critical for fibril formation and accessible to both immunological and small molecule interventions.

🧬 3D Protein Structure

🧬 SNCA — PDB 1XQ8 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity is minimally challenged as SNCA is a unique gene with limited isoforms, though off-target engagement with beta-synuclein and gamma-synuclein family members must be considered for small molecule approaches. Immunotherapy selectivity is inherently high, targeting pathological aggregates rather than native monomeric forms.