New Antimicrotubule Molecules Mimicking Action of Paclitaxel

Several natural products, such as epothilones, discodermolide, and eleutherobin, were found to have a similar mechanism of action as paclitaxel. A recent review outlined many tubulin stabilization natural products and their analogs as anticancer 

Most research has focused on the development of paclitaxel analogs or prodrugs with enhanced specificity MDR reversal and orally effective taxoids have also been developed recently. Meanwhile, scientists have gained insights into the mechanism of action of taxoids at molecular level, that is, binding sites on tubulin and dynamics of tubulin polymerization. It is worth pointing out that the SAR results derived from traditional medicinal chemistry have shown the essential 

It is expected that our SAR and mechanistic knowledge will lead to the rational design of the next generation of taxoids with better properties in the future. New techniques including combinatorial chemistry, genomics, and proteomics will reshape the pharmaceutical industry in the future and accelerate the research and development of new drugs and, undoubtedly, benefit taxoid research. 

After this manuscript was prepared, an important article appeared that should be 

Based on analysis of electronic crystallography and NMR data for the bindings of Taxol and epothilone A to tubulin subunits, it was proposed that they did not share a common pharmacophore (similar binding mode and sites) as hypothesized for a long time, because they bind to their receptors uniquely and independently. Also, the T-shape conformation of Taxol binding to tubulin was supported from this study. 

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