| Literature DB >> 27227380 |
James F Blake1, Michael Burkard1, Jocelyn Chan2, Huifen Chen2, Kang-Jye Chou2, Dolores Diaz2, Danette A Dudley2, John J Gaudino1, Stephen E Gould2, Jonas Grina1, Thomas Hunsaker2, Lichuan Liu2, Matthew Martinson1, David Moreno1, Lars Mueller2, Christine Orr2, Patricia Pacheco2, Ann Qin2, Kevin Rasor1, Li Ren1, Kirk Robarge2, Sheerin Shahidi-Latham2, Jeffrey Stults2, Francis Sullivan1, Weiru Wang2, Jianping Yin2, Aihe Zhou2, Marcia Belvin2, Mark Merchant2, John Moffat2, Jacob B Schwarz2.
Abstract
The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clinically, resistance frequently develops through reactivation of the pathway. Simultaneous targeting of multiple nodes in the pathway, such as MEK and ERK, offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Described herein is the discovery and characterization of GDC-0994 (22), an orally bioavailable small molecule inhibitor selective for ERK kinase activity.Entities:
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Year: 2016 PMID： 27227380 DOI： 10.1021/acs.jmedchem.6b00389
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446