Recent Advances in the Study of the Bioactive Conformation of Taxol

Demystifying Taxol : The structurally complex natural product paclitaxel is among the most important antitumor drugs presently in the clinic. While the mechanism of action is known, the biologically active conformation has been much debated. Herein we summarize the considerable research efforts that have gone into elucidating the bioactive conformation of paclitaxel. magnified image Paclitaxel is one of the most important chemotherapeutic drugs in the fight against cancer. This minireview covers the recent advances in the study of the bioactive conformation of paclitaxel in tubulin/microtubules. The tubulin‐bound structure of paclitaxel has been studied by means of photoaffinity labeling, cryo‐electron microscopy, solid‐state NMR, molecular modeling, MD simulations and the synthesis of conformationally restrained analogues and paclitaxel mimics. The bioactive conformation of paclitaxel is important since it could provide critical information that would allow the design of novel analogues with simpler structures and/or increased potency against cancer.