Vascular endothelial growth factor receptors 1, 2, and 3, Platelet-derived growth factor receptors alpha and beta, and RAF family kinases (BRAF and RAF-1) (VEGFR/PDGFR/RAF)

This target profile represents a cluster of signaling proteins critical for tumor growth, angiogenesis, and lymphangiogenesis. It includes the Vascular Endothelial Growth Factor Receptors (VEGFR1, 2, and 3), which are the primary drivers of blood and lymphatic vessel formation (UniProt P17948, P35968, P35916). The Platelet-Derived Growth Factor Receptors (PDGFRα and PDGFRβ) contribute to pericyte recruitment and the maintenance of tumor stromal pressure, while the RAF family kinases (specifically BRAF and RAF-1) are essential components of the MAPK/ERK pathway regulating cell proliferation and survival (UniProt P16234, P09619, P15056, P04049). Drugs targeting this specific combination, such as sorafenib and regorafenib, act as multi-kinase inhibitors to simultaneously disrupt the tumor's vascular supply and its internal growth signaling (PubChem CID 216239, 11167976). This multi-pronged approach is particularly effective in hypervascular tumors like hepatocellular carcinoma and renal cell carcinoma. However, the broad inhibition of these essential physiological pathways often leads to systemic side effects, including hypertension and dermatological toxicities (PubMed PMID: 24034296).

Other names

VEGFR1-3/PDGFR-alpha/beta/BRAF/RAF-1Multi-kinase inhibitor target profileAngiogenesis and MAPK pathway kinasesVEGFR/PDGFR/RAF signaling complex

Competitive inhibition of the ATP-binding site of multiple receptor tyrosine kinases (VEGFR, PDGFR) and serine/threonine kinases (RAF), leading to suppressed tumor angiogenesis and inhibited tumor cell proliferation (PubChem CID 216239).