rabusertib

Rabusertib (LY2603618) is a potent and selective small molecule inhibitor of checkpoint kinase 1 (CHK1), a serine/threonine kinase that is a central component of the DNA damage response (DDR) network. CHK1 is activated in response to DNA damage or replication stress, where it coordinates cell cycle arrest at the S and G2/M phases to allow for DNA repair. By inhibiting CHK1, rabusertib prevents this arrest, forcing cancer cells with chemotherapy-induced DNA damage to progress through the cell cycle prematurely. This leads to the accumulation of lethal DNA damage, mitotic catastrophe, and apoptosis. Developed by Eli Lilly and Company, rabusertib was investigated as a chemosensitizing agent in combination with drugs like gemcitabine, pemetrexed, and cisplatin for the treatment of advanced solid tumors, including non-small cell lung cancer (NSCLC) and pancreatic cancer. Despite reaching Phase 2 clinical trials, its development was ultimately discontinued.

Other names

rabusertib911222-45-2LY 2603618LY2603618LY-2603618