Definition

An orally available inhibitor of the epidermal growth factor receptor (EGFR), the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET) and vascular endothelial growth factor receptor (VEGFR), with potential anti-angiogenic and antineoplastic activities. Upon oral administration of HA121-28, this agent targets, binds to and inhibits the activity of EGFR, RET and VEGFR. This prevents EGFR-, RET- and VEGFR-mediated signaling, and may lead to the induction of apoptosis and inhibition of tumor growth in EGFR-, RET- and VEGFR-overexpressing cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. Dysregulation of RET activity plays a key role in the development and progression of a variety of cancers. Expression of VEGFR is upregulated in a variety of tumor cell types; it plays a key role in the migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and tumor cell death.