EPHB4

Ephrin type-B receptor 4

Score: 0.564 Price: $0.56 Low Druggability Status: active Wiki: EPHB4

🧠 Neurodegeneration

HYPOTHESES

1

PAPERS

24

KG EDGES

85

DEBATES

1

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:

9

Known Drugs:

1

Approved:

1

In Clinical Trials:

0

Drug Pipeline (1 compounds)

1 Approved

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

🧬 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.

3D Protein Structure

PDB: Open in RCSB AlphaFold model

Interactive 3D viewer powered by RCSB PDB / Mol*. Use mouse to rotate, scroll to zoom.

Clinical Trials (7)

Relevant trials from ClinicalTrials.gov

Active

0

Completed

3

Total Enrollment

824

By Phase

PHASE1: 4 · PHASE2: 1 · PHASE3: 1 · Unknown: 1

Chronic Myelogenous Leukemia (CML) - Follow on: Study of BMS-354825 in Subjects With CML Completed

PHASE3 NCT00123474 n=724

Myeloid Leukemia, Chronic, Chronic-Phase

Interventions: dasatinib, dasatinib, dasatinib

Sponsor: Bristol-Myers Squibb | Started: 2005-07

Safety and Efficacy of Pegylated IFN-alpha 2B Added to Dasatinib in Newly Diagnosed Chronic Phase Myeloid Leukemia Completed

PHASE2 NCT01725204 n=40

Leukemia, Myeloid, Chronic-Phase

Interventions: Dasatinib + PegIFN

Sponsor: Norwegian University of Science and Technology | Started: 2012-09

Phase I (PH I) Mad Refractory Solid Tumor Study Completed

PHASE1 NCT00099606 n=60

Neoplasms

Interventions: Dasatinib

Sponsor: Bristol-Myers Squibb | Started: 2004-07

Dasatinib in Combination With Chemotherapy for Relapsed or Refractory Core Binding Factor Acute Myeloid Leukemia Withdrawn

PHASE1 NCT02680951

Acute Myeloid Leukemia

Interventions: Dasatinib, Fludarabine, Cytarabine

Sponsor: Emory University | Started: 2015-12

Study of Ipilimumab and Dasatinib Combination Therapy in Patients With Chronic or Accelerated Chronic Myeloid Leukemia Withdrawn

PHASE1 NCT00732186

Leukemia, Myeloid, Chronic

Interventions: Ipilimumab

Sponsor: Bristol-Myers Squibb | Started: 2009-08

Study of Dasatinib, Androgen Deprivation Therapy and Radiation Withdrawn

PHASE1 NCT01826838

Prostate Cancer

Interventions: Dasatinib

Sponsor: Brown University | Started: 2013-01

The Randomized Study of Dasatinib and High-Dose Imatinib (600mg) in Suboptimal Responder Available

Unknown NCT00854841

Chronic Myeloid Leukemia

Interventions: Dasatinib and Imatinib

Sponsor: Pusan National University Hospital

Linked Hypotheses (1)

Ephrin-B2/EphB4 Axis Manipulation0.645

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (1)

associated with (4)

RASA1→EPHB4RYR2→EPHB4SCN1A→EPHB4ROBO1→EPHB4

co discussed (8)

NTN1→EPHB4HSPG2→EPHB4P2RY12→EPHB4P2RX7→EPHB4AQP4→EPHB4

▸ Show 3 more

EPHB4→SMPD1EPHB4→C1QAEPHB4→CERS2

implicated in (1)

EPHB4→carcinoma

interacts with (6)

TP53→EPHB4EPHB4→SRCEPHB4→AKTEPHB4→TP53EPHB4→EFNB1

▸ Show 1 more

Debate History (1)

Should EPHB4 (Ephrin type-B receptor 4) be prioritized as a therapeutic target f2026-04-21