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Figure 48 Structures of synthetic microtubule stabilizers.

considerably less complex than their natural-product counterparts. Thus, it is likely that these compounds can serve as more amenable lead structures for medicinal chemistry. GS-64 107, a small heterobicycle that shows all the mechanistic hallmarks expected of an microtubule stabilizer, has recently been described.237 This compound was found to possess micromolar cytotoxicity, roughly 1000 times less potent than paclitaxel. Homologated estradiol 108 was likewise found to be a promoter of microtubule assembly at the micromolar level.238 Other workers have identified sulfonamide 109 via a high-throughput screening strategy. This compound has been reported to stabilize microtubules in vitro with potency similar to paclitaxel; however, it is far less potent as a cytotoxin.239 A similar divergence between in vitro and cell-based potency was observed for synthetic borneol esters such as 110.240

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