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Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors
Published on: January 20, 2023
Macrocyclic inhibitors of hsp90
Victoria A Johnson1, Erinprit K Singh, Lidia A Nazarova
1Department of Chemistry and Biochemistry, San Diego State University, CA 92182-1030, USA.
Current Topics in Medicinal Chemistry
|June 12, 2010
Summary
Heat shock protein 90 (Hsp90) inhibitors, primarily macrocycles, show promise for cancer therapy. This review details nine macrocycles targeting Hsp90, their potency, and affected oncogenic client proteins.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Heat shock proteins (HSP) are crucial for cellular survival under stress.
- Heat shock protein 90 (Hsp90) is vital for oncogenic protein maturation and stabilization.
- Hsp90 is a validated therapeutic target in cancer treatment.
Purpose of the Study:
- To review the discovery and development of macrocyclic Hsp90 inhibitors.
- To highlight the potency and selectivity of these inhibitors.
- To identify Hsp90 client proteins affected by these inhibitors.
Main Methods:
- Literature review of Hsp90 inhibitors.
- Analysis of macrocyclic scaffold properties for Hsp90 binding.
- Compilation of data on inhibitor potency and affected client proteins.
Main Results:
- Nine macrocyclic Hsp90 inhibitors have been discovered and developed.
- Macrocyclic structures provide rigid scaffolds for selective Hsp90 interaction.
- Inhibitors demonstrate varying potencies and affect diverse oncogenic client proteins.
Conclusions:
- Macrocycles represent a promising class of Hsp90 inhibitors for cancer therapy.
- The development of selective Hsp90 inhibitors is advancing.
- Targeting Hsp90 offers a strategic approach to cancer treatment by disrupting multiple oncogenic pathways.
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