STX17

Syntaxin-17

Score: 0.552 Price: $0.55 Medium Druggability Status: active Wiki: STX17

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

716

DEBATES

3D Protein Structure

🧬 STX17 — PDB 4WY4 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.46

Clinical Stage

Phase II

Target Class

Structural Protein

Safety

0.30

Druggability Analysis

Drug Development0.40

Structural Tractability0.70

Target Class0.50

Safety Profile0.30

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (4 compounds)

1 Preclinical

Therapeutic Areas:

Neurodegenerative diseases (Huntington's disease, Parkinson's disease, Alzheimer's disease) Protein aggregation disorders Autophagy enhancement therapy Motor neuron diseases Lysosomal storage disorders

Druggability Rationale: STX17 presents low druggability challenges due to its role as a structural SNARE protein lacking classical deep binding pockets typical of enzymes or receptors. While PDB structures (1.4 Å resolution) provide atomic-level detail, the mechanism of action relies on protein-protein interactions rather than small molecule binding, making traditional ligand discovery difficult; however, indirect modulators like trehalose in Phase 2 demonstrate that autophagy enhancement through STX17 pathway engagement remains therapeutically viable.

Mechanism: STX17-targeting drugs would enhance or modulate autophagosome-lysosome fusion by facilitating SNARE complex assembly, thereby improving autophagic clearance of misfolded proteins and damaged organelles. This mechanism is particularly relevant for neurodegenerative diseases characterized by protein aggregation.

Drug Pipeline (4 compounds)

1 Preclinical

Known Drugs:

Trehalose (phase2) — Neurodegeneration, autophagy enhancement

MRT67307 (STX17 inhibitor tool compound) (research) — Research tool for autophagy-related studies

NSC185058 (preclinical) — Autophagy modulation, protein clearance

Spermidine (phase1) — Autophagy induction, neurodegeneration

Structural Data:

PDB (3) ✓AlphaFold ✓Cryo-EM —

4WY4 7BV4 7BV6

UniProt: E9PQU9

Binding Pocket Analysis:

STX17 structures (PDB: 4WY4, 7BV4, 7BV6) reveal the characteristic coiled-coil SNARE domain architecture with limited hydrophobic pockets; binding sites are primarily allosteric regulatory surfaces rather than classical ATP or substrate pockets. AlphaFold modeling confirms intrinsically disordered regions that may serve as dynamic interaction interfaces for SNARE complex assembly modulators.

🔮 Predicted Protein Structure (AlphaFold)

🔮 STX17 — AlphaFold P56962 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity is complicated by STX17's role in a conserved SNARE fusion machinery shared across multiple cellular compartments and homology with other syntaxin isoforms (STX4, STX11, STX12), necessitating careful validation to avoid off-target autophagy disruption in non-neuronal tissues. Antibody or allosteric modulation approaches may offer better isoform selectivity than direct inhibition.