All seven taccalonolides present microtubule stabilizing action, but serious differences in anti-proliferative potencies were known, with IC50 values including the low nanomolar range for taccalonolide AA to the low micromolar range for taccalonolide Page1=46. These studies show that various Ganetespib manufacturer taccalonolides get microtubule stabilizing properties and that major structure activity relationships exist. In vivo antitumor evaluations of taccalonolides E, An and D show that all of the molecules has in vivo antitumor activity. Microtubule stabilizers are among the most important classes of anticancer therapeutics utilized in the clinic today. The taxoid microtubule backing paclitaxel is widely used in the treatment of solid tumors, including breast, ovarian and lung cancers for over 10 years like a single agent and in conjunction with targeted therapies. In spite of their clinical application, mRNA the short-comings of paclitaxel and the next generation semi-synthetic taxoid, docetaxel, include natural and acquired drug resistance and dose limiting toxicities. 1 Two new microtubule stabilizers have already been approved for clinical use in the past 3 years: the epothilone ixabepilone and the taxoid cabazitaxel, which circumvent some, although not most of the shortcomings of first and second-generation microtubule stabilizers. 2, 3 These microtubule stabilizing drugs all bind to the internal lumen of the intact microtubule at the taxoid binding site, which in turn causes a stabilization of microtubule protofilament interactions and therefore lowers the dynamic nature of microtubules. MAP kinase inhibitor 4 Two additional courses of microtubule stabilizers that do not bind within the site have been separated from nature: laulimalides/peloruside An and the taccalonolides. Laulimalide and peloruside A have recently been shown to bind to the exterior of the microtubule in a site different from the taxoid binding site, but result in microtubule stabilization effects not exactly similar to the taxoids. 5 The taccalonolides are unique in they do not bind directly to microtubules/tubulin and don’t improve the polymerization of purified tubulin in biochemical assays. 6 microtubule stabilizing effects to be caused by The ability of the taccalonolides through a totally different mechanism of action and a special binding site encouraged our fascination with understanding this class of molecules. Intense efforts within the last three years have discovered a big selection of interesting compounds from the roots and rhizomes of Tacca variety, including 25 taccalonolides, denoted as taccalonolides A Y. 7 15 However, there were limited biological studies around the taccalonolides. In 2003, we first reported the microtubule stabilizing actions of taccalonolides An and E.