Inhibition of osimertinib-resistant epidermal growth factor receptor EGFR-T790M/C797S.

ABSTRACT: Precision medicine has revolutionized the treatment of patients in EGFR driven non-small cell lung cancer (NSCLC). Targeted drugs show high response rates in genetically defined subsets of cancer patients and markedly increase their progression-free survival as compared to conventional chemotherapy. However, recurrent acquired drug resistance limits the success of targeted drugs in long-term treatment and requires the constant development of novel efficient inhibitors of drug resistant cancer subtypes. Herein, we present covalent inhibitors of the drug resistant gatekeeper mutant EGFR-L858R/T790M based on the pyrrolopyrimidine scaffold. Biochemical and cellular characterization, as well as kinase selectivity profiling and western blot analysis, substantiate our approach. Moreover, the deve

SUBMITTER: Lategahn J 

PROVIDER: S-EPMC6886544 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature