Tubulin as a target for anticancer drugs

Nature provides a large spectrum of agents that either inhibit the polymerization of tubulin or prevent the disassembly of microtubules. Some of them are already used as anticancer drugs, but acquired resistance limits their application. Recently, a variety of new substances that inhibit tubulin aggregation have been synthesized or isolated from natural sources. Examples are vinflunine, the combretastatin analog AC-7700, indanocine, the sulfonamide T-138067, oncocidin A1, natural and modified dolastatins, and cryptophycins. Among the substances which stabilize microtubules, the taxanes play the dominant role. A second generation of synthetically modified derivatives is in development as exemplified by IDN-5109. A number of other natural products, such as the epothilones, eleutherobin, sarcodictyin and discodermolide, share the mode of action with the taxanes, but exceed them in potency and activity in multidrug-resistant cells. However, toxicity and availability might prevent their medical application.