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

This target group consists of four distinct receptor tyrosine kinases: Vascular endothelial growth factor receptors 1, 2, and 3, and Platelet-derived growth factor receptor beta. These receptors are critical regulators of the vascular system, where VEGFRs primarily drive the proliferation and migration of endothelial cells to form new blood and lymphatic vessels (UniProt P35968, P35916). PDGFRβ plays a complementary role by recruiting pericytes and smooth muscle cells to stabilize these nascent vessels, ensuring vascular integrity and maturation (UniProt P09619). In the context of oncology, the over-activation of these signaling pathways promotes pathological angiogenesis, which is essential for tumor growth, survival, and metastatic spread (PubMed PMC3136669). Therapeutic agents targeting this group are typically small-molecule multi-kinase inhibitors that bind to the intracellular ATP-binding site of the receptors. By simultaneously inhibiting VEGFRs and PDGFRβ, these drugs can both prevent the formation of new tumor vessels and disrupt the stability of existing ones. This dual approach is widely utilized in treating various malignancies, including renal cell carcinoma, hepatocellular carcinoma, and gastrointestinal stromal tumors. Beyond cancer, these receptors are also implicated in ophthalmic diseases characterized by neovascularization, such as wet age-related macular degeneration and diabetic retinopathy.

Other names

VEGFR1VEGFR2VEGFR3PDGFRBFLT1KDRFLT4PDGFR-betaVEGF and PDGF receptors

Small molecule inhibition of the intracellular tyrosine kinase domains of VEGFR1, VEGFR2, VEGFR3, and PDGFRβ through competitive binding at the ATP-binding site, preventing receptor autophosphorylation and downstream signaling.