Definition

An orally bioavailable inhibitor of the receptor tyrosine kinases (RTKs) hepatocyte growth factor receptor (c-Met; HGFR), vascular endothelial growth factor receptor type 2 (VEGFR2), AXL and MER, with potential anti-angiogenesis and antineoplastic activities. Upon oral administration, zanzalintinib targets and binds to c-Met, VEGFR2, AXL and MER, and prevents their RTK activity. This blocks c-Met/VEGFR2/AXL/MER-mediated signal transduction pathways, and inhibits the proliferation and migration of c-Met-, VEGFR2-, AXL- and MER-overexpressing tumor cells. c-Met, overexpressed in many tumor cell types, plays a critical role in tumor formation, proliferation, invasion and metastasis, and contributes to tumor resistance. VEGFR2, overexpressed in certain tumor types, plays an essential role in angiogenesis and the proliferation, survival, migration and differentiation of endothelial cells. AXL and MER, both members of the TAM (Tyro3, Axl and Mer) family of RTKs, are overexpressed by many tumor cell types. They play key roles in tumor cell proliferation, survival, invasion, angiogenesis and metastasis, and their expression is associated with enhanced immunosuppression, drug resistance and poor prognosis.