PHA-665752 is an oxindole-based, ATP-competitive c-Met and Ron inhibitor with IC50 potencies of 9 nM, and 68 nM, respectively. [1] It is >50-fold selective compared to a broad panel of both tyrosine and serine-threonine kinases. In cellular studies, PHA-665752 inhibits HGF-stimulated and constitutive c-Met phosphorylation as well as downstream signal transduction mediators such as Gab-1, Akt, phospholipase C gamma, and focal adhesion kinase. Inhibition of c-Met phosphorylation is dose-dependent and correlates well with tumor growth inhibition.

PHA-665752 induced apoptosis and cell cycle arrest in BaF3.TPR-MET cells at an IC50 of 60 nM. [2] Additionally, PHA-665752 has been suggested to inhibit lung tumorigenesis in mutant K-Ras mice and may be a formidable treatment for NSCLC. [3]