ULK1

Unc-51 like autophagy activating kinase 1

Score: 0.614 Price: $0.61 Low Druggability Status: active Wiki: ULK1

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

1386

DEBATES

3D Protein Structure

🧬 ULK1 — PDB 4WNO Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.42

Clinical Stage

Phase I

Target Class

Kinase

Safety

0.40

Druggability Analysis

Drug Development0.15

Structural Tractability0.85

Target Class0.85

Safety Profile0.40

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Preclinical

Druggability Rationale: ULK1 is a moderately druggable target (0.60 score) as a kinase with excellent structural characterization (17 PDB structures, 1.07 Å resolution) and proven ligand tractability demonstrated by SBI-0206965. However, the medium druggability score reflects challenges in achieving selectivity within the kinase superfamily and potential off-target liabilities common to broad-spectrum kinase inhibitors.

Mechanism: Small molecule activators or inhibitors of ULK1 kinase activity to modulate autophagy

Drug Pipeline (1 compounds)

1 Preclinical

Known Drugs:

SBI-0206965 (preclinical) — Research tool compound

Structural Data:

PDB (17) ✓AlphaFold ✓Cryo-EM ✓

4WNO 4WNP 5CI7 6HYO 6MNH+12 more

UniProt: O75385

🧬 3D Protein Structure

🧬 ULK1 — PDB 4WNO Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

Selectivity against closely-related kinases (ULK2, ULK3, ATG1) and broader kinase off-target effects presents a significant challenge given the conserved catalytic domain. Achieving selective ULK1 modulation over isoforms will likely require targeting allosteric pockets or utilizing structure-based design approaches leveraging the high-resolution PDB structures available.