HSP90 Inhibitors Blocking Multiple Oncogenic Signaling Pathways for the Treatment of Cancer

  • Fen Jiang
  • Xiao-Li Xu
  • Qi-Dong YouEmail author
Part of the Heat Shock Proteins book series (HESP, volume 17)


Heat shock protein 90 (HSP90) is an ATP-dependent molecular chaperone which plays important roles in the development of cancer. Inhibition of the HSP90 chaperone function can disrupt multiple cancer dependent signaling pathways and result in potent anti-cancer effects, which has been a promising anti-cancer strategy. Up to now, HSP90 inhibitors with different mechanisms have been developed, including HSP90 N-terminal inhibitors (pan-isoform and isoform selective), C-terminal inhibitors and HSP90-cochaperone protein-protein interaction (PPI) inhibitors. In this chapter, we will review the current development of HSP90 inhibitors as anti-cancer agents.


Cancer GRP94 HSP90-CDC37 PPI HSP90 inhibitor Isoform selective TRAP1 





complete response


C-terminal domain




dose-limiting toxicities


epigallocatechin gallate


endoplasmic reticulum


esophageal squamous cell carcinoma




glucose-regulated protein 94


hepatocyte growth factor


Heat shock protein


homogeneous time-resolved fluorescence


insulin-like growth factors








multiple myeloma


maximum tolerance dose


non-small cell lung cancer


N-terminal domain


protein-protein interaction


partial response




stable disease


succinate dehydrogenase


surface plasmon resonance


treatment-related adverse events


TNF-α–related apoptosis-inducing ligand


transgenic adenocarcinoma of the mouse prostate


tumor necrosis factor receptor-associated protein-1



This work is supported by Projects 81872737 and 81773639 of the National Natural Science Foundation of China; 2632018ZD15 of the Key Program of China Pharmaceutical University; 2017ZX0-9302003, and 2018ZX09711002-003-006 of the National Major Science and Technology Project of China (Innovation and Development of New Drugs).


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization and Department of Medicinal Chemistry, School of PharmacyChina Pharmaceutical UniversityNanjingChina

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