Inhibitor binding to Hsp90: a review of thermodynamic, kinetic, enzymatic, and cellular assays

Curr Protein Pept Sci. 2014 May;15(3):256-82. doi: 10.2174/1389203715666140331115032.

Abstract

This manuscript reviews published Hsp90 inhibitors and Hsp90-binding compounds. The main goal of the article is to overview the structures of existing Hsp90 inhibitors and to draw correlations between compound structure and binding affinity. Furthermore, it is important to emphasize all thermodynamic binding data especially the data that includes the enthalpies, entropies, heat capacities, and the volumes of binding. This information is important for the goal of drawing the principles of a more rational drug design. The distinction between the observed and the intrinsic binding parameters should also be emphasized. Out of nearly 280 compounds surveyed, most could be classified to three chemical groups (resorcinol-bearing, geldanamycin derivatives, and purine-pyrimidine derivatives) and only few of them have determined intrinsic thermodynamic parameters other than the dissociation/inhibition constant. Since most compounds are being developed as anticancer agents, the available cell growth inhibition data is also included. Possible limitations of the use of enzymatic inhibition and the cancer cell growth inhibition data is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / metabolism*
  • Enzyme Inhibitors / pharmacology*
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors*
  • HSP90 Heat-Shock Proteins / chemistry
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Kinetics
  • Protein Binding
  • Thermodynamics

Substances

  • Enzyme Inhibitors
  • HSP90 Heat-Shock Proteins