PDGFRB

Platelet-derived growth factor receptor beta

Score: 0.629 Price: $0.63 Medium Druggability Status: active Wiki: PDGFRB

🧠 Neurodegeneration

HYPOTHESES

2

PAPERS

44

KG EDGES

326

DEBATES

0

3D Protein Structure

🧬 PDGFRB — PDB 3MJG Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Druggability & Clinical Context

Druggability

Medium

Score: 0.50

Clinical Stage

Approved

Target Class

Kinase

Safety

0.60

Druggability Analysis

Drug Development1.00

Structural Tractability0.70

Target Class0.85

Safety Profile0.60

Key Metrics

PDB Structures:

2

Known Drugs:

3

Approved:

3

In Clinical Trials:

0

Drug Pipeline (3 compounds)

3 Approved

Therapeutic Areas:

Alzheimer's disease (blood-brain barrier dysfunction) Other neurodegenerative diseases (Parkinson's, ALS) Cerebrovascular pathology Cancer (existing approved indication) Stroke and ischemic brain injury Pericyte dysfunction disorders

Druggability Rationale: PDGFRB is highly druggable (0.90 score) as a receptor tyrosine kinase with an ATP-binding pocket amenable to small molecule inhibition, demonstrated by three FDA-approved kinase inhibitors (imatinib, dasatinib, sunitinib) already targeting this protein. High-resolution crystal structures (1.5 Å) and AlphaFold models provide excellent structural guidance for rational drug design and optimization.

Mechanism: Small molecule inhibitor of receptor tyrosine kinase activity

Drug Pipeline (3 compounds)

3 Approved

Known Drugs:

Imatinib (approved) — cancer

Dasatinib (approved) — cancer

Sunitinib (approved) — cancer

Structural Data:

PDB (2) ✓AlphaFold ✓Cryo-EM —

UniProt: E5RII0

Binding Pocket Analysis:

The ATP-binding pocket is well-characterized through high-resolution crystal structures (PDB: 2L6W, 3MJG), featuring the conserved kinase domain architecture with hinge region interactions typical of type I kinase inhibitors. The pocket accommodates diverse small molecules as evidenced by the approved multi-targeted inhibitors, with opportunities for selectivity optimization through exploitation of peripheral binding regions.

🧬 3D Protein Structure

🧬 PDGFRB — PDB 3MJG Click to expand interactive 3D viewer

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

Selectivity & Safety Considerations

PDGFRB shares significant homology with PDGFRA and other receptor tyrosine kinases, presenting selectivity challenges; existing approved drugs show variable selectivity profiles, with dasatinib demonstrating broader kinase inhibition than imatinib. Achieving selective PDGFRB inhibition while minimizing off-target effects on related kinases remains a key optimization consideration.

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 (8)

Relevant trials from ClinicalTrials.gov

Active

0

Completed

8

Total Enrollment

967

By Phase

PHASE2: 7 · PHASE3: 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

Therapy of Early Chronic Phase CML With Gleevec Completed

PHASE2 NCT00048672 n=50

Leukemia, Myeloid, Chronic-Phase

Interventions: Gleevec

Sponsor: M.D. Anderson Cancer Center | Started: 2001-03

Imatinib Mesylate in Treating Patients With Liver Metastasis From a Gastrointestinal Stromal Tumor Completed

PHASE2 NCT00764595 n=5

Gastrointestinal Stromal Tumor, Metastatic Cancer

Interventions: imatinib mesylate

Sponsor: Translational Research Center for Medical Innovation, Kobe, | Started: 2008-10

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

Study Tests The Safety And Effectiveness Of SU011248 In Patients With Non-Small Cell Lung Cancer Having Brain Metastases Completed

PHASE2 NCT00372775 n=66

Non-Small Cell Lung Cancer

Interventions: Sunitinib

Sponsor: Pfizer | Started: 2007-03

Combination of Recombinant Human IL-21 (rIL-21) and Sunitinib in Stage IV Renal Cell Carcinoma Patients Completed

PHASE2 NCT00617253 n=9

Cancer, Renal Cell Carcinoma

Interventions: recombinant interleukin-21, sunitinib, recombinant interleukin-21

Sponsor: Novo Nordisk A/S | Started: 2007-07-12

Sunitinib Malate Before and After Surgery in Treating Patients With Previously Untreated Metastatic Kidney Cancer Completed

PHASE2 NCT01024205 n=43

Kidney Cancer

Interventions: sunitinib malate, laboratory biomarker analysis, adjuvant therapy

Sponsor: Barts and the London School of Medicine and Dentistry | Started: 2007-08

Sunitinib in Treating Patients With Kidney Cancer That Cannot Be Removed by Surgery Completed

PHASE2 NCT00459979 n=30

Kidney Cancer

Interventions: sunitinib malate, conventional surgery

Sponsor: Case Comprehensive Cancer Center | Started: 2007-03

Linked Hypotheses (2)

Pericyte Contractility Reset via Selective PDGFR-β Agonism0.684

Vascular mural cell degeneration precedes and exacerbates parenchymal pathology0.625

Linked Experiments (0)

No linked experiments

Scoring Dimensions

Knowledge Graph (20)

activates (6)

PDGFRB → STAT5

PDGFRB → VEGFB

PDGFRB → STING

PDGFRB → CSF1R

PDGFRB → IGF1R

...and 1 more

associated with (4)

PDGFRB → neurodegeneration

PDGFRB → Ph_like_ALL

PDGFRB → ANGPT1

PDGFRB → PDGFB

causes (1)

PDGFRB → Fahr_disease

co discussed (1)

PDGFRB → TGFB1

contributes to (3)

PDGFRB → arrhythmias

PDGFRB → NTRK3

inhibits (1)

interacts with (1)

PDGFRB → ANGPT1

regulates (1)

PDGFRB → PDGFB

therapeutic target (2)

PDGFRB → LMNA

Debate History (0)

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