Tubulin/Microtubules: Still a Promising Target for New Chemotherapeutic Agents

Most investigators would agree that the ideal chemotherapeutic agent should be 1) directed at a validated target; 2) potent, preferably active at nanomolar or subnanomolar concentrations; 3) schedule independent, even active in noncycling cells; 4) active against drug-resistant cells; and 5) less toxic or ideally not toxic to normal cells. In this issue of the Journal, Leoni et al. (1) suggest that indanocine, a synthetic antimitotic indanone, possesses all of these properties. Further studies will be needed to prove this convincingly, but even if indanocine is not the ideal compound, one may eventually be found or synthesized. The antimitotic drugs include a diverse group of compounds, most of which are natural products, whose varied mechanisms of action result in a common end point: mitotic arrest (2,3). The majority of these agents induce mitotic arrest by interacting with tubulin, and the simplest classification divides these agents into