Spongistatins as tubulin targeting agents

Recently identified novel agents that disrupt tubulin polymerization includ e synthetic spiroketal pyrans (SPIKET) targeting the spongistatin binding s ite of P-tubulin. These agents exhibit anticancer activity by disrupting no rmal mitotic spindle assembly and cell division as well as inducing apoptos is. At nanomolar concentrations, the SPIKET compound SPIKET-P caused tubuli n depolymerization in cell-free turbidity assays and exhibited potent cytot oxic activity against cancer cells as evidenced by destruction of microtubu le organization, and prevention of mitotic spindle formation in human breas t cancer cells. SPIKET compounds represent a new class of tubulin targeting agents that show promise as anti-cancer drugs.