MLCK

Myosin light chain kinase

Score: 0.520 Price: $0.52 Low Druggability Status: active Wiki: MLCK

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 MLCK — PDB 3OT8 Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.40

Clinical Stage

Phase II

Target Class

Kinase

Safety

0.50

Druggability Analysis

Drug Development0.30

Structural Tractability0.70

Target Class0.85

Safety Profile0.50

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (2 compounds)

2 Preclinical

Druggability Rationale: MLCK is moderately druggable (0.60 score) as a kinase target with well-characterized structural data (1.8 Å resolution, PDB: 6C6M) and existing research tools (ML-7, ML-9) demonstrating proof-of-concept inhibition. However, medium druggability reflects challenges in achieving selectivity across the kinase superfamily and potential off-target effects that may complicate clinical translation beyond phase 2.

Mechanism: MLCK inhibitors block the phosphorylation of myosin light chains, thereby reducing cytoskeletal contraction and stabilizing tight junctions at the blood-brain barrier and endothelial surfaces. This mechanism reduces vascular permeability and preserves barrier integrity in conditions characterized by excessive leakage or cytoskeletal dysfunction.

Drug Pipeline (2 compounds)

2 Preclinical

Known Drugs:

ML-7 (research_tool) — myosin light chain kinase inhibition

ML-9 (research_tool) — myosin light chain kinase inhibition

Structural Data:

PDB (1) ✓AlphaFold ✓Cryo-EM —

6C6M

UniProt: Q15746

🧬 3D Protein Structure

🧬 MLCK — PDB 3OT8 Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

MLCK selectivity is complicated by structural homology with other kinases; isoform selectivity between MLCK and MLCK-like kinases (e.g., MLCK-L) must be carefully characterized to avoid off-target cardiovascular or smooth muscle effects. Tight junction-specific targeting could be achieved through BBB permeability optimization rather than kinase selectivity alone.