Ispinesib mesilate.: Antimitotic drug, KSP inhibitor.

In the search for novel mitotic targets for the development of antineoplastic agents, Homo sapiens Eg5 kinesin spindle protein (KSP, HsEg5/KSP) was identified. KSP is a member of a subfamily of kinesins that are involved in centrosome separation and bipolar spindle formation during mitosis. It has been shown to function exclusively in mitosis and is preferentially overexpressed in malignant cells. Inhibition of KSP interferes with the formation of the bipolar spindle required for proper separation and lining of chromosomes during mitosis, which ultimately leads to cell death. KSP inhibitors may therefore effectively interfere with mitosis while showing an improved therapeutic index. Ispinesib mesilate (715992, SB-715992, formerly CK-0238273) is one such KSP inhibitor that was found to be more selective for KSP over other members of the kinesin family. It effectively induced tumor regression in several preclinical models. Ispinesib was chosen for further development as an antimitotic agent and has shown efficacy in phase I and 11 trials in patients with solid tumors.