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JNJ-38877605 is a small-molecule ATP-competitive inhibitor of the catalytic activity of c-Met.

Extensive evidence that c-Met signaling is involved in the progression and spread of several cancers and an enhanced understanding of its role in disease have generated considerable interest in c-Met and HGF asmajor targets in anti-cancer drug development.

In vitro: JNJ-38877605 showed ~600-fold selectivity for c-Met compared with a panel of ~250 diverse tyrosine and serine-threonine kinases and was found to potently inhibit HGF-stimulated and constitutively activated c-Met phosphorylation in vitro [1].

In vivo: JNJ-38877605 showed excellent oral bioavailability approaching 100% in all examined species. In addition, JNJ-38877605 in a single dose was observed toinhibit Met phosphorylation in tumor xenografts for up to16 h. Inhibition of Met phosphorylation was associated withdose-dependent tumor growth inhibition using a range of oral dosing regimens [2].

Clinical trial: A Safety and Dose-finding Study of JNJ-38877605 in Patients With Advanced or Refractory Solid Tumors.

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