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Studies on the natural product, novobiocin, have elucidated specific modifications that increase Hsp90 inhibition. Through diversification of the sugar appendage, coumarin core and benzamide side chain of novobiocin, structurally unique scaffolds have been synthesized. These structural adaptations have produced potent cytotoxic agents, such as KU135, which are prepared more simply than those that contain the noviose sugar. These analogues have been evaluated against two cancer cell lines and demonstrated low micromolar anti-proliferative activity.
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