The development of taxol and docetaxel into two of the worlds most important anticancer drugs (Taxol® and Taxotere®) has proven the stabilization of cellular microtubules to be a clinically relevant mechanistic principle.
Microtubule stabilization thus also provides a promising conceptual framework for the future discovery of new and improved antitumor agents and this is not in the least reflected in the significant number of new agents (taxane and non-taxane based) that are currently undergoing clinical evaluation in humans.
Until the recognition of the tubulin-polymerizing activity of epothilones in 1995, the capacity for microtubule stabilization appeared to be associated solely with taxol-like structures, but the last decade has witnessed the discovery of a number of new and structurally diverse microtubule stabilizing agents, which do not bear any structural resemblance with taxol.
These compounds are all characterized by the ability to induce tubulin polymerization in vitro and their gross cellular profiles are similar.
At the same time, it is becoming increasingly clear that not all microtubule stabilizers are made equal and that differences exist between individual agents with regard to their interactions with tubulin, in the way they affect the cellular microtubule network and in their effects on cell proliferation and the induction of apoptosis.
This includes, e.g., the discovery of compounds which do not bind to the taxol site on b-tubulin or the identification of