Antia Laboratories Inc.

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CAS Number: 1196681-44-3

Chemical Name: N-(4-(2-Amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

Molecular Formula: C25H19ClF2N4O4

Molecular Weight: 512.89

BMS-777607 is currently under clinical evaluation, inhibits both ligand stimulated and constitutive Met phosphorylation. As a result, HGF induced scattering and migration were observed to be inhibited when cells were treated with this compound. BMS-777607 also inhibited tumor cell proliferation in vitro in tumor lines in which Met was constitutively active. In addition, cell cycle analysis demonstrated G1 arrest as a result of drug treatment. In vivo, tumor growth inhibition was observed with BMS- 777607 in the GTL-16 human gastric tumor model in which Met is amplified and activated. Using this same model, Met receptor phosphorylation in tumor tissue from mice treated orally with varying doses of BMS- 777607 was inhibited in a dose-dependent manner. In vivo activity was also assessed pharmacodynamically in GTL-16 tumor bearing mice using Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI). Consistent with the role Met plays in angiogenesis, DCE-MRI results demonstrated inhibition of contrast agent uptake in a  dose-responsive manner.

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