Ispinesib

Ispinesib (SB-715992), a potent and selective small molecule inhibitor of KSP, functions by inhibiting KSP ATPase and is 40000 times more selective for KSP compared to other kinesins. In preclinical studies, ispinesib inhibited growth in a wide range of human and murine cell lines with IC50 values of 1.2-9.5nm. Treatment of SKOV3 ovarian tumour cells in vitro with 20nm of ispinesib, or a Colo 205 colon cancer murine xenograft model with 30mgkg-1 of intraperitoneal ispinesib, caused mitotic arrest with cells demonstrating unseparated centrosomes and monopolar mitotic spindles. Tumour growth delay was observed in xenograft models of colon (HT29, Colo201, Colo205), non-small cell lung (Calu-3) and pancreatic (Panc-01) cancers.