BLU-945, a potent and selective next-generation EGFR TKI, has antitumor activity in models of osimertinib-resistant non-small-cell lung cancer.

ABSTRACT:

Introduction

Despite the availability of several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), most patients with non-small-cell lung cancer (NSCLC) eventually develop resistance to these agents. Notably, EGFR_C797S mutations confer resistance to the third-generation EGFR-TKI osimertinib and no approved post-osimertinib targeted pharmacology options are currently available. BLU-945 is a novel, reversible, and orally available next-generation EGFR-TKI that selectively targets EGFR-activating (EGFRm) and resistance mutations (including EGFR_C797S) with nanomolar potency while sparing wild-type EGFR in vitro.

Methods

In vitro activity of BLU-945 as a single agent and in combination with osimertinib was tested in engineered EGFR-

SUBMITTER: Lim SM 

PROVIDER: S-EPMC11497503 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature