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Medicina is published by MDPI from Volume 54 Issue 1 (2018). Articles in this Issue were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence. Articles are hosted by MDPI on mdpi.com as a courtesy and upon agreement with Lithuanian Medical Association, Lithuanian University of Health Sciences, and Vilnius University.
Open AccessArticle

Binding of Natural and Synthetic Inhibitors to Human Heat Shock Protein 90 and Their Clinical Application

Institute of Biotechnology, Vilnius University, Lithuania
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Medicina 2011, 47(8), 413; https://doi.org/10.3390/medicina47080062
Received: 1 August 2011 / Accepted: 31 August 2011 / Published: 5 September 2011
This review describes the recent progress in the field of heat shock protein 90 (Hsp90) inhibitor design. Hsp90 is a heat shock protein with a molecular weight of approximately 90 kDa. Hsp90 is considered a good anticancer target because its inhibition leads to inactivation of its numerous client proteins participating in various signaling and other processes involved in cancer progression. Numerous Hsp90 inhibitors-leads currently tested in clinical trials are presented in this review. Furthermore, this review emphasizes the application of biophysical binding assays in the development of Hsp90 inhibitors. The binding of designed lead compounds to various Hsp90 constructs is measured by isothermal titration calorimetry and thermal shift assay. These assays provide a detailed energetic insight of the binding reaction, including the enthalpy, entropy, heat capacity, and the Gibbs free energy. A detailed description of the binding energetics helps to extend our knowledge of structure-activity relationships in the design of more potent inhibitors. The most active compounds are then tested for their absorption, distribution, metabolism, elimination, toxicity, and activity against cancer cell lines.
Keywords: Hsp90 inhibitors; anticancer activity; isothermal titration calorimetry; thermal shift assay; ThermoFluor® Hsp90 inhibitors; anticancer activity; isothermal titration calorimetry; thermal shift assay; ThermoFluor®
MDPI and ACS Style

Petrikaitė, V.; Matulis, D. Binding of Natural and Synthetic Inhibitors to Human Heat Shock Protein 90 and Their Clinical Application. Medicina 2011, 47, 413.

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