Discovery and optimization of a potent and selective triazolopyridinone series of c-Met inhibitors
Copyright policy )Discovery and optimization of a potent and selective triazolopyridinone series of c-Met inhibitors
Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is an attractive target for small molecule drug discovery. Herein, we report the discovery of a structurally diverse series of carbon-linked quinoline triazolopyridinones, which demonstrates nanomolar inhibition of c-Met kinase activity. This novel series of inhibitors exhibits favorable pharmacokinetics as well as potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver pharmacodynamic model.
- Amgen (United Kingdom) United Kingdom
- Amgen (United States) United States
Male, Models, Molecular, Hepatocyte Growth Factor, Pyridones, Antineoplastic Agents, Proto-Oncogene Proteins c-met, Triazoles, Crystallography, X-Ray, Rats, Rats, Sprague-Dawley, Mice, Cell Line, Tumor, Drug Discovery, Microsomes, Liver, Quinolines, Animals, Humans, Phosphorylation, Protein Kinase Inhibitors, Signal Transduction
Male, Models, Molecular, Hepatocyte Growth Factor, Pyridones, Antineoplastic Agents, Proto-Oncogene Proteins c-met, Triazoles, Crystallography, X-Ray, Rats, Rats, Sprague-Dawley, Mice, Cell Line, Tumor, Drug Discovery, Microsomes, Liver, Quinolines, Animals, Humans, Phosphorylation, Protein Kinase Inhibitors, Signal Transduction
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