Vascular endothelial growth factor receptor 1, 2, 3 and Platelet-derived growth factor receptor beta (VEGFR1/2/3/PDGFRβ)

The Vascular Endothelial Growth Factor Receptors (VEGFR1, VEGFR2, and VEGFR3) and Platelet-Derived Growth Factor Receptor beta (PDGFRβ) are a group of distinct receptor tyrosine kinases that collectively regulate the development and maintenance of the vascular and lymphatic systems (UniProt P17948, P35968, P35916, P09619). VEGFR2 is the primary driver of angiogenesis, while VEGFR1 and VEGFR3 modulate vascular signaling and promote lymphangiogenesis, respectively. PDGFRβ is essential for the recruitment of pericytes that stabilize blood vessels. In many cancers, these receptors are overexpressed or hyperactivated, facilitating the pathological angiogenesis required for tumor growth and metastasis. Sorafenib is a multi-kinase inhibitor that targets the intracellular kinase domains of these receptors, effectively blocking the signaling pathways that support tumor vascularization and cell proliferation (Wilhelm et al., 2004; PubChem CID 216239). While therapeutically effective in treating hepatocellular and renal cell carcinomas, the systemic inhibition of these pathways is associated with significant safety concerns, including hypertension and hand-foot skin reaction (StatPearls, 'Sorafenib'; FDA Label, Nexavar). This target entry represents a composite profile of four distinct proteins that are simultaneously inhibited by certain small-molecule drugs.

Other names

FLT1KDRFLT4PDGFRBVascular endothelial growth factor receptor 1Vascular endothelial growth factor receptor 2Vascular endothelial growth factor receptor 3Platelet-derived growth factor receptor betaCD309CD310

Competitive inhibition of the ATP-binding site within the intracellular tyrosine kinase domains of VEGFR1, VEGFR2, VEGFR3, and PDGFRβ, preventing receptor autophosphorylation and the activation of downstream pro-angiogenic and proliferative signaling pathways (Wilhelm et al., 2004; PubChem CID 216239).