In the past few decades, the development of heat shock protein 90 (Hsp90) inhibitors for cancer treatment has not stopped. About twenty compounds have been evaluated in the clinical trials, but the FDA approved none of them because of toxic effects and/or not enough efficacies. Insufficient isoform selectivity has been considered as one of the reasons for these failures recently. Therefore, developing isoform-selective Hsp90 inhibitors could probably make great progress in searching for therapeutic agents for cancer as well as many other diseases. Here, we summarized classic pan-inhibitors of Hsp90 based on the classification of binding sites and illustrated design strategies applied in the drug discovery. We summed up current isoform-specific Hsp90 inhibitors including their discovery processes and potential indications.

在过去的几十年里，用于癌症治疗的热休克蛋白 90 (Hsp90) 抑制剂的开发并未停止。大约有 20 种化合物已在临床试验中进行了评估，但由于毒性作用和/或没有足够的功效，FDA 没有批准任何一种化合物。最近，异构体选择性不足被认为是这些失败的原因之一。因此，开发异构体选择性 Hsp90 抑制剂可能会在寻找癌症和许多其他疾病的治疗剂方面取得重大进展。在这里，我们根据结合位点的分类总结了 Hsp90 的经典泛抑制剂，并说明了在药物发现中应用的设计策略。我们总结了当前异构体特异性 Hsp90 抑制剂，包括它们的发现过程和潜在适应症。