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HSP90 inhibitors beyond oncology: optimization and mechanism insights in non-oncological diseases

Xingyu Yin1, Huangliang Shu1, Danni Wang1

  • 1State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China; Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

Drug Discovery Today
|November 7, 2025
PubMed

Insights

Heat shock protein 90 (HSP90) inhibitors show promise for treating non-oncological diseases like infections and neurodegenerative disorders. Further research into optimized inhibitor design and mechanisms is needed to realize their full therapeutic potential.

Area of Science:

  • Molecular Biology
  • Pharmacology
  • Biochemistry

Background:

  • Heat shock protein 90 (HSP90) is crucial for cellular proteostasis, aiding protein folding and maturation.
  • HSP90 inhibitors are well-studied in oncology but their non-oncological applications are underexplored.
  • This review systematically discusses HSP90 inhibitors for non-cancerous conditions.

Purpose of the Study:

  • To review the therapeutic potential of HSP90 inhibitors in non-oncological diseases.
  • To analyze recent advances in inhibitor optimization and signaling pathways.
  • To propose strategies for overcoming clinical translation challenges.

Main Methods:

  • Literature review of HSP90 inhibitors in viral/fungal infections, inflammatory disorders, and neurodegenerative diseases.
  • Analysis of signaling pathways and HSP90-client protein interactions.
  • Examination of inhibitor optimization and clinical translation strategies.

Main Results:

  • HSP90 inhibitors demonstrate potential in treating viral infections, fungal infections, inflammatory conditions, and neurodegenerative diseases.
  • Recent advances include optimized inhibitor design and a deeper understanding of signaling pathways.
  • Challenges in clinical translation for non-oncological indications were identified.

Conclusions:

  • HSP90 inhibitors offer therapeutic possibilities beyond cancer, particularly for infectious and neurodegenerative diseases.
  • Optimized inhibitor design and enhanced mechanistic understanding are key to unlocking their potential.
  • Strategic approaches are proposed to facilitate clinical translation for these indications.
Keywords:
HSP90client proteinscompound structural optimizationmechanism analysisnon-oncological diseases

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