(R)-Crizotinib

(R)-Crizotinib is a dual inhibitor of c-Met and anaplastic lymphoma kinase (ALK; IC50s = 8 and 20 nM, respectively, in a cell-based assay).{22302} It is selective for c-Met and ALK over several other receptor- and non-receptor tyrosine kinases, including Ron, Tie2, Abl, LCK, and VEGFR2 (IC50s = 0.08, 0.448, 1.159, 2.741, and >10 µM, respectively). (R)-Crizotinib selectively inhibits the proliferation of cancer cell lines with MET amplifications over cancer cell lines with MET or EGFR mutations (IC50s = 5-10, 472-1,284, and 767-787 nM, respectively).{22301} It induces apoptosis in MET-amplified EBC-1 and NCI H1993 lung cancer cells when used at a concentration of 100 nM. (R)-Crizotinib (25 mg/kg) reduces tumor volume in an EBC-1 mouse xenograft model. Formulations containing crizotinib have been used in the treatment of metastatic, relapsed, or refractory ALK-positive cancers.