Discovery of anticancer agents for Drug-resistant Lung Cancer

Abstract

Lung cancer is one of the most frequently diagnosed cancer types in the world. Non-small cell lung cancer(NSCLC) accounts for 85% of total lung cancer, so that numerous chemotherapies focus on treating NSCLC. Especially, EGFR inhibitors have introduced the concept of targeted therapy to NSCLC. Despite of its potent efficacy on NSCLC, however, long-term administration of EGFR inhibitors causes chronic problem: acquired resistance against administrated drug. Therefore, novel trial to overcome this problem was needed and our group has designed and synthesized series of compounds targeting ARK5. Our group has performed docking study of compounds on ARK5, and successfully synthesized derivatives based on the result of docking study. And these compounds were tested to measure anti-proliferative activities on gefitinib resistant NSCLC cell line. As the result, compounds with hundreds of GI50 values(nM) were obtained and chemical library consisting of these ARK5 inhibitory compounds has been established. With this chemical library in this study, mechanism study of ARK5 or development of novel inhibitors would be suggested for further study.