SAR125844 is a potent and highly selective c-Met inhibitor with potential antineoplastic activity. Upon intravenous administration, SAR125844 binds to c-Met, thereby disrupting c-Met-mediated signal transduction pathways. SAR125844 displayed nanomolar activity against the wild-type kinase (IC50 value of 4.2 nmol/L) and the M1250T and Y1235D mutants. Broad biochemical profiling revealed that SAR125844 was highly selective for MET kinase. SAR125844 inhibits MET autophosphorylation in cell-based assays in the nanomolar range, and promotes low nanomolar proapoptotic and antiproliferative activities selectively in cell lines with MET gene amplification or pathway addiction.
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