KU-596 is a second-generation C-terminal heat shock protein 90 KDa (Hsp90) modulator based on the natural product, novobiocin. KU-596 has been shown to induce Hsp70 levels and manifest neuroprotective activity through induction of the heat shock response. A ring-constrained analog of KU-596 was designed and synthesized to probe its binding orientation and ability to induce Hsp70 levels. Compound 2 was found to exhibit comparable or increased activity compared to KU-596, which is under clinical investigation for the treatment of neuropathy.

中文翻译：

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具有神经保护活性的受环约束的Hsp90 C末端抑制剂的合成和评价

KU-596是第二代C末端热激蛋白90 KDa（Hsp90）调节剂，基于天然产物新霉素。KU-596已显示出诱导Hsp70水平并通过诱导热休克反应表现出神经保护活性。设计并合成了环状约束的KU-596类似物，以探测其结合方向和诱导Hsp70水平的能力。发现化合物2与KU-596相比具有可比的或增加的活性，KU-596正在临床研究中以治疗神经病。