Fig. 7

Targeting therapy of HSP90. a Stage 1: targeting pan-HSP90 isoforms (from 1990s), including HSP90 NBD ATPase inhibitors, MD inhibitors and CTD inhibitors. b Stage 2: targeting HSP90 isoforms with high selectivity (from 2000s). Selective binding sites of HSP90 isoforms have been respectively reported, leading to discovery of inhibitors with high selectivity, including TRAP-1 selective inhibitors, GRP94 selective inhibitors, HSP90β selective inhibitors and HSP90α selective inhibitors. Besides, eHSPs selective inhibitors have also been designed by introducing impermeable membrane moieties into HSP90 inhibitors. c Stage 3: targeting PPIs between HSP90 and co-chaperones (from 2010s), including HSP90-CDC37 PPI inhibitors, HSP90-HOP PPI Inhibitors, HSP90-Aha1 PPI Inhibitors and HSP90-P23 PPI inhibitors. d Stage 4: design of multi-specific molecules based on HSP90 (from 2020s), including CHAMPs and PROTACs