Titre : Discovery of AMG 337, A Potent and Selective Inhibitor of c-Met with High Unbound Exposure and Robust, Extended In Vivo Antitumor Activity.
Endroit : Pavillon Roger-Gaudry, salle G-815 à 11 h.
Hôte : Professeure Hélène Lebel.

La conférence sera prononcée (en anglais) par Dr. Alessandro Boezio, scientifique principal à Amgen Inc. (Cambridge, MA).

Résumé : The receptor tyrosine kinase c-Met and hepatocyte growth factor (HGF), its endogenous ligand, are implicated in several cellular processes relevant to cancer, including cell proliferation, cell migration, and invasive growth. Deregulation of the c-Met/HGF pathway can lead to tumorigenesis and metastasis. Amplification of the MET gene, the overexpression of c-Met and/or HGF, and constitutive activation conferred by sequence mutations are some of the mechanisms of deregulation that have been found in human cancers. The potential blockade of both ligand-dependent and ligand-independent activity of c-Met by an ATP-competitive small molecule inhibitor acting via the intracellular kinase domain is an appealing strategy for the treatment of cancer. We previously reported the discovery of potent, orally active c-Met inhibitors, however, each series suffers from its own unique liabilities. Efforts to improve upon these inhibitors led to the discovery of a series of c-Met inhibitors leading to AMG 337. This presentation will describe the design, synthesis, pharmacokinetics and in vivo efficacy of this class of compounds. AMG 337 is currently in Phase 2 clinical trials for the treatment of cancer.

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