Development and Biological Evaluation of Potent and Specific Inhibitors of Mitotic Kinesin Eg5

Abstract

Monastrol was the first specific but moderate inhibitor of the mitotic kinesin Eg5 to be identified. It proved to be useful for studies of cell division and is thought to have anticancer potential. We have synthesized a small chemical library of monastrol analogues and tested them for Eg5 inhibition in vitro and for arresting mitosis of cultured cells. We found that dimethylenastron (1) is more than 100-times more potent than monastrol in both cases.