Journal of Medicinal Chemistry p. 2328 - 2342 (2016)
Update date:2022-08-03
Topics:
Boezio, Alessandro A.
Copeland, Katrina W.
Rex, Karen
K Albrecht, Brian
Bauer, David
Bellon, Steven F.
Boezio, Christiane
Broome, Martin A.
Choquette, Deborah
Coxon, Angela
Dussault, Isabelle
Hirai, Satoko
Lewis, Richard
Lin, Min-Hwa Jasmine
Lohman, Julia
Liu, Jingzhou
Peterson, Emily A.
Potashman, Michele
Shimanovich, Roman
Teffera, Yohannes
Whittington, Douglas A.
Vaida, Karina R.
Harmange, Jean-Christophe
Deregulation of the receptor tyrosine kinase mesenchymal epithelial transition factor (MET) has been implicated in several human cancers and is an attractive target for small molecule drug discovery. Herein, we report the discovery of compound 23 (AMG 337), which demonstrates nanomolar inhibition of MET kinase activity, desirable preclinical pharmacokinetics, significant inhibition of MET phosphorylation in mice, and robust tumor growth inhibition in a MET-dependent mouse efficacy model.
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