VEGFR TK inhibitor efficacy depends on conformational differences

摘要

Anticancer drugs known as tyro-sine kinase (TK) inhibitors block critical TK activity and disrupt vascular endothelial growth factor receptor (VEGFR) signaling. Four structurally diverse VEGFR TK inhibitors have been approved to treat renal cell carcinoma, a cancer that has been linked to aberrant VEGF signaling; however, the therapies' distinct clinical efficacies and VEGF-related safety profiles suggest that each inhibits its shared molecular target differently. In their Feature Article, Michele McTigue et al. (pp. 18281-18289) determined the potencies, time-dependence, selectivities, and X-ray structures of drug-kinase complexes for the VEGFR TK inhibitor class and found unique drug-kinase interactions that correspond to differences in potency and ligand efficiency.