Simultaneous inhibition of multiple kinases has been suggested to provide synergistic effects on tumor growth inhibition and tumor resistance. In a recent study, researchers have shown that resistance to epidermal growth factor receptor kinase (EGFR) inhibitors could be overcome if given in combination with aurora kinase (AURK) inhibitors in non-small cell lung cancer (NSCLC) cells. Additionally, the mitotic kinase, AURK has demonstrated improved efficacy in mutant KRAS expressing NSCLC cells. In a previous study, Kurup et al. identified N4-(3-bromophenyl)pyrrolo[2,3-d]pyrimidin-4-amine, 1 as a micromolar, dual inhibitor of AURK and EGFR. We have synthesized varied analogs of 1 to evaluate the importance of the 4-substitution on EGFR and AURK inhibition. An improvement in the potency and selectivity of EGFR and AURK inhibition was observed. The synthesis, kinase inhibitory activities, and antiproliferative effects of these compounds in NSCLC cells will be presented.

Design, synthesis, and evaluation of dual AURK and EGFR inhibitors for non-small cell lung cancer

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.