The taxoid microtubule stabilizer paclitaxel is popular in treating solid tumors, including lung, ovarian and breast cancers for over ten years like a single agent and in conjunction with targeted therapies. Notwithstanding their clinical application, the shortcomings Cediranib clinical trial of paclitaxel and the 2nd generation semi-synthetic taxoid, docetaxel, include innate and acquired drug resistance and dose limiting toxicities. These microtubule stabilizing drugs all bind for the internal lumen of the intact microtubule at the taxoid binding site, which Plastid causes a stabilization of microtubule protofilament interactions and thus decreases the dynamic nature of microtubules. Two additional courses of microtubule stabilizers that do not bind within the site have been isolated from nature: laulimalides/peloruside An and the taccalonolides. Laulimalide and peloruside A have been recently demonstrated to bind to the exterior of the microtubule at a site distinct from the taxoid binding site, but bring about microtubule stabilization consequences not quite similar to the taxoids. The taccalonolides are unique in that they don’t bind directly to microtubules/tubulin and do not boost the polymerization of purified tubulin in biochemical assays. The capability of the taccalonolides to trigger microtubule stabilizing effects through a special binding site and a totally different mechanism of action prompted our fascination with understanding this class of molecules. Extreme efforts within the last three years have discovered a big variety of interesting LY2484595 compounds from the roots and rhizomes of Tacca species, including 25 taccalonolides, denoted as taccalonolides A B. 7 15 But, there have been limited biological studies to the taccalonolides. In 2003, we first described the microtubule stabilizing activities of taccalonolides An and E. 16 Follow up studies showed early structure activity relationships for your anti-proliferative activities of taccalonolides A, E, W and D. The anti-proliferative potencies of the 4 taccalonolides in HeLa cells were all-in the middle nanomolar range. In this study we isolated three previously undescribed taccalonolides designated: AA, Z and AB. The mechanisms of action of all taccalonolides were evaluated and compared to taccalonolides An and E.