JNJ-38877605 is an ATP-competitive c-Met inhibitor (IC50: 4 nM), 600-fold selective for c-Met than 200 other tyrosine and serine-threonine kinases.

c-Met:4 nM

JNJ-38877605 shows more than 600-fold selectivity for c-Met compared with more than 200 other diverse tyrosine and serine-threonine kinases and also potently inhibits HGF-stimulated and constitutively activated c-Met phosphorylation in vitro. In EBC1, GTL16, NCI-H1993, and MKN45 cells, JNJ-38877605 (500 nM) leads to a significant reduction of phosphorylation of Met and RON, another key player in invasive growth. A recent study shows that JNJ-38877605 is involved in modulating secretion of IL-8, GROa, uPAR and IL-6 in GTL16 cells.

In mice bearing established GTL16 xenografts, JNJ-38877605 (40 mg/kg/day, p.o., total 3day) results in a statistically marked decrease in the plasma levels of human IL-8 (0.150-0.050 ng/mL) and GROα (0.080-0.030 ng/mL). While concentrations of uPAR in the blood become reduced to more than 50% at the same dose.

Animal Models: GTL16 cells are inoculated subcutaneously into the right posterior flank (or both right and left posterior flanks,for determination of uPAR and IL-6) of 6-week-old immuno-deficient nu/nu female mice on Swiss CD1 background. Formulation: JNJ-38877605 is dissolved in PBS. Dosages: ≤40 mg/kg/day. Administration: Administered via p.o.