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VEGFR-2, FGFR2, and PDGFRα (VEGFR-2, FGFR2, PDGFRα)

Target
VEGFR-2, FGFR2, PDGFRα
Molecular classification
Receptor tyrosine kinase, Transmembrane receptor, Member of FGFR family (FGFR1–4), Member of PDGFR family (PDGFRα, PDGFRβ)
01

Overview

Vascular endothelial growth factor receptor 2 is a glycoprotein transmembrane receptor (230 kDa mature form) encoded by the *KDR* gene on chromosome 4q11-12. It is the principal receptor for VEGF-A and mediates critical signaling for angiogenesis and vascular permeability in endothelial and some precursor cells. VEGFR-2 activation drives the growth of new blood vessels in normal development and in disease, particularly tumors, making it a major target for anti-angiogenic cancer therapies[1][2][3][4][7]. Fibroblast growth factor receptor 2 is a transmembrane receptor tyrosine kinase involved in developmental processes and angiogenesis. FGFR2 is activated by binding to fibroblast growth factors (e.g., FGF-2), driving cell proliferation and differentiation. Dysregulation contributes to tumorigenesis and skeletal disorders, making it a therapeutic target, especially in certain cancers[5][6]. Platelet-derived growth factor receptor alpha is a transmembrane receptor tyrosine kinase primarily expressed in mesenchymal cells. It is activated by PDGF ligands, mediating cell proliferation, survival, and migration. Aberrant PDGFRα signaling is implicated in cancer and fibrotic diseases, and inhibitors are used therapeutically in selected tumor types[5][6]. Context: These three RTKs often co-activate or cooperate in tumor angiogenesis, pericyte recruitment, and vessel stabilization[5]. Drugs may target one or more of these kinases for maximal anti-angiogenic effect or to overcome drug resistance in cancers where angiogenesis is driven by multiple growth factor pathways[6]. No spelling errors or misname detected in the provided target; listing targets together is common in multi-kinase inhibition strategies. Overall, VEGFR-2, FGFR2, and PDGFRα are well-established, clinically validated therapeutic targets belonging to the receptor tyrosine kinase family, primarily involved in angiogenesis and cancer, and are each individually targeted by approved anti-cancer drugs[1][5][6].

Other names
Kinase insert domain receptor (KDR)fetal liver kinase 1 (Flk-1, mouse)VEGF receptor 2CD332CD140a
02

Mechanism of action

VEGFR-2: Inhibition of receptor autophosphorylation and downstream signal transduction by targeting the ATP-binding site of the kinase domain. Blockade of ligand binding (VEGF-A, VEGF-C, VEGF-D). FGFR2: Inhibition of FGFR2 kinase activity, blocking phosphorylation and signal transduction. PDGFRα: Inhibition of PDGFRα kinase activity, preventing downstream signaling.

03

Biological functions

Angiogenesis (formation of new blood vessels)Vasculogenesis (development of blood vessels during embryogenesis)Vascular permeabilityEndothelial cell proliferation, migration, survivalCell proliferationDifferentiationAngiogenesis (particularly pericyte recruitment and vascular stabilization)Tissue repair and developmentTissue growth and repairAngiogenesis
04

Disease associations

Cancer (tumor angiogenesis)Cardiovascular diseaseInflammationOther diseases involving abnormal vascular growthCancer (various solid tumors)Skeletal dysplasiaCardiovascular and developmental disordersCancer (e.g., gastrointestinal stromal tumors, other solid tumors)Fibrosis
05

Safety considerations

HypertensionProteinuriaIncreased risk of bleeding or thrombosisGastrointestinal perforationDelayed wound healingOcular toxicityHyperphosphatemiaStomatitisCardiac toxicityFluid retentionEdema
06

Interacting drugs

sunitinib

10 more in the full profile.

07

Biomarkers

Expression levels of VEGFR-2 in tumorsSerum/plasma VEGF-A concentrationsSoluble VEGFR-2 (circulating)FGFR2 gene mutations/fusions (especially in cholangiocarcinoma and other cancers)PDGFRα mutation or overexpression (notably in GIST and other cancers)

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