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FIGURE 6.17 Reversibility of the covalent DNA-ET-743 complex.

Because of the complexity of the ET-743 structure, extensive studies have been carried out on the preparation of simpler analogues. Among them, the most important is phthalascidin,74 with an activity similar to that of the natural product, where the phthalimino group plays a similar role to the spirotetrahydroisoquino-line unit in ET-743.75 Another related compound is PM00104/50, which has recently begun Phase I clinical trials for the treatment of solid tumors.76

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