Conformational landscape of the epidermal growth factor receptor kinase reveals a mutant specific allosteric pocket.

ABSTRACT: Activating mutations within the epidermal growth factor receptor (EGFR) kinase domain give rise to several cancers including Non-Small Cell Lung Cancer (NSCLC). Small molecule inhibitors targeted at these mutants have proven to be clinically successful drugs. These molecules are ATP competitive and rapidly result in the emergence of resistance. Recently Jia et al. [Nature, 2016, 534, 129-132] reported a small molecule inhibitor (called EAI045) that binds at an allosteric pocket, does not compete with ATP and displays high potency and selectivity towards certain activating mutants (L858R, T790M, L858R/T790M) of EGFR, with IC₅₀ values ranging from 3 nM to 49 nM. We present here a study combining extensive molecular dyn

SUBMITTER: Kannan S 

PROVIDER: S-EPMC6001276 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature