Pan- and isoform-specific inhibition of Hsp90: Design strategy and recent advances

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.

Automated summary

In the past few decades, the development of Hsp90 inhibitors for cancer treatment has been ongoing. However, many compounds evaluated in clinical trials were not approved by the FDA due to toxic effects and lack of efficacy. Insufficient isoform selectivity has been identified as one of the reasons for these failures. Therefore, the development of isoform-specific Hsp90 inhibitors could lead to significant progress in finding therapeutic agents for cancer and other diseases. This article provides a summary of classic pan-inhibitors of Hsp90 and discusses the design strategies used in drug discovery. It also summarizes current isoform-specific Hsp90 inhibitors, including their discovery processes and potential indications.