CYT997, a synthetic small molecule optimized for antiproliferative activity in a panel of cell-based assays, in which the compound shows an IC₅₀ of between 1 and 100 nmol/L across a panel of cancer cell lines. The compound inhibits the polymerization of tubulin with an IC₅₀ of ～3 μmol/L.CYT997 causes a significant increase of cells in the G2-M phase of the cell cycle.Caspase-3 activation is also observed in cells treated with CYT997 along with the generation of poly(ADP-ribose) polymerase.CYT997 exhibits vascular disrupting activity as measured in vitro by effects on the permeability of human umbilical vein endothelial cell monolayers, and in vivo by effects on tumor blood flow. CYT997 possesses a useful combination of pharmacologic and pharmacokinetic properties and has considerable potential as a novel anticancer agent. ^[1]