Discovery and development of antimitotic agents that inhibit tubulin polymerisation for the treatment of cancer

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Abstract
Antimitotic agents have generated considerable interest among cytotoxic agents due to the tremendous success of the taxanes and the widespread use of the Vinca alkaloids in clinical oncology. Renewed interest in tubulin polymerisation inhibitors has been generated by the hope that non-multi-drug resistance (MDR) substrates that interact with tubulin at sites near to, overlapping with or different from those of the taxanes or Vinca alkaloids can be discovered. In this article, new antimitotic agents that inhibit tubulin polymerisation for the treatment of cancer are reviewed, with greater emphasis being focused on the small molecule colchicine site binders. Compounds that induce metaphase arrest, by other novel mechanisms, are summarised. Results of clinical trials of drug candidates that fall into these classes are also briefly discussed. The patent literature was surveyed from January 1998 through May 2002.