ABSTRACT

The cryptophycins are potent antitumor depsipeptides œrst isolated from terrestrial blue-green algae. Initial cellular mechanism of action studies showed them to be associated with the inhibition of mitotic spindle function. This characterization puts the cryptophycins into one of the clinically very important classes of anticancer agents, such as the vinca alkaloids (vincristine, vinblastine, and vinorelbine) and the taxanes (taxol and taxotere) that act primarily on the cellular microtubule structure and function. Extensive preclinical studies have demonstrated that the cryptophycins are highly

9.1 Introduction ........................................................................................................................... 219 9.2 Isolation and Characterization of the Cryptophycins ............................................................220 9.3 Mechanism of Action of the Cryptophycins ......................................................................... 221

9.3.1 Cellular Mechanism of Action of Cryptophycin 52 (LY355703) ............................. 221 9.3.2 Effects of Cryptophycin 52 (LY355703) on Microtubule Polymerization In Vitro...223