Heat shock protein 90 inhibitors as broad spectrum anti-infectives

Ankit K Rochani1, Meetali Singh, Utpal Tatu

  • 1Department of Biochemistry, Indian Institute of Science, Bangalore-12, India.

Insights

Parasitic microbes rely on Heat Shock Protein 90 (Hsp90) for survival and virulence. Targeting Hsp90 offers a promising strategy for developing new anti-infective drugs, potentially by repurposing existing cancer therapies.

Area of Science:

  • Microbiology and Molecular Biology
  • Drug Discovery and Development
  • Parasitology

Background:

  • Pathogenic microbes face significant stress within host environments, necessitating robust stress response mechanisms for survival.
  • Heat Shock Protein 90 (Hsp90), a key stress protein, plays a critical role in the growth and pathogenesis of various parasitic organisms.
  • Hsp90 is recognized for its essential functions in microbial stress response and virulence, making it a potential therapeutic target.

Purpose of the Study:

  • To review the current status of Hsp90 as a drug target for infectious diseases.
  • To explore the potential of Hsp90 inhibitors as anti-infective agents.
  • To investigate the feasibility of repurposing existing Hsp90 inhibitors, developed for cancer treatment, for combating parasitic infections.

Main Methods:

  • Literature review of existing research on Hsp90 function in pathogenic microbes.
  • Analysis of data on Hsp90 inhibitors, including their development status, toxicity, pharmacokinetics, and pharmacodynamics.
  • Exploration of drug repurposing strategies for Hsp90 inhibitors in the context of infectious diseases.

Main Results:

  • Hsp90 is crucial for the survival and virulence of diverse pathogenic microbes, including Candida, Giardia, Plasmodium, and Trypanosoma.
  • Significant research exists on Hsp90 inhibitors, primarily for anti-cancer applications, with extensive preclinical and clinical data available.
  • Existing Hsp90 inhibitors have well-characterized safety profiles and pharmacokinetic properties, suggesting potential for repurposing.

Conclusions:

  • Hsp90 represents a viable and attractive drug target for developing novel anti-infective therapies.
  • Repurposing established Hsp90 inhibitors offers a strategic advantage due to existing safety and efficacy data, potentially accelerating drug development.
  • Further research and pharmaceutical solutions are needed to fully realize the potential of Hsp90 inhibitors in the infectious disease market.

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