Structure-activity exploration of a small-molecule allosteric inhibitor of T790M/L858R double mutant EGFR.

ABSTRACT: EGFR is a protein kinase whose aberrant activity is frequently involved in the development of non-small lung cancer (NSCLC) drug resistant forms. The allosteric inhibition of this enzyme is currently one among the most attractive approaches to design and develop anticancer drugs. In a previous study, we reported the identification of a hit compound acting as type III allosteric inhibitor of the L858R/T790M double mutant EGFR. Herein, we report the design, synthesis and in vitro testing of a series of analogues of the previously identified hit with the aim of exploring the structure-activity relationships (SAR) around this scaffold. The performed analyses allowed us to identify two compounds 15 and 18 showing improved inhibition of double mutant EGFR with respect to the

SUBMITTER: Foschi F 

PROVIDER: S-EPMC9665079 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature