Article
Inhibitors that stabilize a closed RAF kinase domain conformation induce dimerization.
Nature chemical biology - 1 Jul 2013
Lavoie Hugo, Thevakumaran Neroshan, Gavory Gwenaëlle, Li John J, Padeganeh Abbas, Guiral Sébastien, Duchaine Jean, Mao Daniel Y L, Bouvier Michel, Sicheri Frank, Therrien Marc
Abstract excerpt
RAF kinases have a prominent role in cancer. Their mode of activation is complex but critically requires dimerization of their kinase domains. Unexpectedly, several ATP-competitive RAF inhibitors were recently found to promote dimerization and transactivation of RAF kinases in a RAS-dependent manner and, as a result, undesirably stimulate RAS/ERK pathway-mediated cell growth. The mechanism by which these...
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