k858

Description: K-858 is a novel, potent and ATP-uncompetitive inhibitor of mitotic kinesin Eg5 that has potential antitumor activity. K858 is a potent inhibitor of replication and induces apoptosis in breast tumor cells, independently from the tumor phenotype. This anti-proliferative response of tumor cells to K858 can be limited by the contemporaneous over-expression of survivin; consequently, the reduction of survivin levels, obtained with AKT inhibitors, can sensitize tumor cells to K858-induced apoptosis. K858 blocked centrosome separation, activated the spindle checkpoint, and induced mitotic arrest in cells accompanied by the formation of monopolar spindles. K858 induces mitotic arrest and growth inhibition through the activation of the Mad2-mediated spindle checkpoint. K858 induces mitotic cell death in cancer cells but not in normal cells. K858 induces mitotic arrest, apoptosis, and cell growth inhibition and has no effect on microtubule polymerization.

References: Cancer Res. 2009 May 1; 69(9):3901-9; Invest New Drugs. 2016 Aug; 34(4):399-406.