Syntheses of Anti-Lung Cancer Agents(1/2)

This project is aimed to synthesize a new series of ALK inhibitors and identify the drug candidate by using pre-lead MPT0G8 class as motif that could be specifically used in the treatment of lung cancer. Preliminary data indicated three pre-lead compounds can substantially inhibit ALK activity similar to Alectinib, slightly better than Crizotinib. They can significantly inhibit drug resistant ALK-G1202R kinase activity with a sub nM range of IC50 values. They also effectively suppress cancer cells growth of KRAS mutant A549 and EGFR-resistant H1975 lines, better than Crizotinib and Ceritinib. Since lung cancer is a leading cause of cancer-related death in the world, it would be an opportunity to develop a targeting various ALK mutants inhibitors with good PK profile and in v^-vo efficacy for treatment of lung cancer.