EPHB4

Ephrin type-B receptor 4

Score: 0.650 Price: $0.65 Low Druggability Status: active Wiki: EPHB4

🧠 Neurodegeneration

HYPOTHESES

PAPERS

KG EDGES

DEBATES

3D Protein Structure

🧬 EPHB4 — PDB 2HLE Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Low

Score: 0.43

Clinical Stage

Approved

Target Class

Kinase

Safety

0.50

Druggability Analysis

Drug Development0.75

Structural Tractability0.70

Target Class0.85

Safety Profile0.50

Key Metrics

PDB Structures:

Known Drugs:

Approved:

In Clinical Trials:

Drug Pipeline (1 compounds)

1 Approved

Therapeutic Areas:

Alzheimer's disease neurodegeneration synaptic dysfunction cognitive decline vascular dementia stroke recovery axonal regeneration

Druggability Rationale: EPHB4 is highly druggable with a druggability score of 0.90, supported by its classification as a receptor tyrosine kinase with well-characterized ATP binding pocket (best PDB resolution 1.05 Å across 9 structures). The clinical precedent of dasatinib approval for CML demonstrates that EPH family kinases can be successfully inhibited with small molecules, and the extensive structural data (9 PDB entries, AlphaFold availability) enables structure-guided drug design.

Mechanism: Small molecule inhibitor of receptor tyrosine kinase activity

Drug Pipeline (1 compounds)

1 Approved

Known Drugs:

dasatinib (approved) — chronic myeloid leukemia

Structural Data:

PDB (9) ✓AlphaFold ✓Cryo-EM —

2BBA 2E7H 2HLE 2QKQ 6FNI+4 more

UniProt: Q541P7

Binding Pocket Analysis:

EPHB4 possesses a canonical ATP binding pocket typical of receptor tyrosine kinases, with high-resolution structural data (1.05 Å) revealing conserved hinge region interactions and potential allosteric regulatory sites. The extended kinase domain structure provides opportunities for both ATP-competitive and allosteric inhibition strategies for improved selectivity.

🧬 3D Protein Structure

🧬 EPHB4 — PDB 2HLE Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

EPHB4 selectivity represents a key challenge due to high sequence homology with other EPH receptor kinases (EPHA/EPHB family), which may result in off-target effects on synaptic plasticity, axon guidance, and vascular function. Achieving isoform selectivity will require structure-based optimization to exploit subtle binding pocket differences between EPH family members.