Vascular endothelial growth factor receptor 1, 2, and 3; Hepatocyte growth factor receptor; and TAM family receptors (TYRO3, AXL, MERTK) (VEGFR1/2/3, c-Met, TAM)

This target profile comprises a specific set of receptor tyrosine kinases (RTKs) that collectively drive tumor progression, angiogenesis, and therapeutic resistance. The Vascular Endothelial Growth Factor Receptors (VEGFR1, 2, and 3) are essential for the formation of new blood and lymphatic vessels, which supply nutrients to the tumor (UniProt P17948, P35968, P35916). Hepatocyte growth factor receptor (c-Met) and the TAM family (TYRO3, AXL, and MERTK) are frequently implicated in the development of resistance to standard anti-angiogenic therapies and promote tumor invasion and metastasis (UniProt P08581, Q06418, P30530, Q12866). Furthermore, the TAM receptors play a critical role in immune homeostasis and efferocytosis; their inhibition can enhance anti-tumor immune responses by modulating the activity of macrophages and dendritic cells. Multi-kinase inhibitors targeting this entire group, such as cabozantinib, are utilized to treat advanced malignancies like renal cell carcinoma and hepatocellular carcinoma by simultaneously disrupting multiple survival and escape pathways (FDA Label: Cabometyx).

Other names

Flt-1 (VEGFR1)KDR (VEGFR2)Flt-4 (VEGFR3)MET (c-Met)TAM receptors (TYRO3, AXL, MERTK)Hepatocyte growth factor receptorUFO (AXL)MER (MERTK)SKY (TYRO3)

Small molecule inhibition of the intracellular tyrosine kinase domains of VEGFR1, VEGFR2, VEGFR3, MET, AXL, MERTK, and TYRO3, preventing autophosphorylation and downstream signaling through pathways such as PI3K/AKT, MAPK/ERK, and JAK/STAT.