Macrocyclic Inhibitors of Hsp90

Title: Macrocyclic Inhibitors of Hsp90

Volume: 10 Issue: 14

Author(s): Victoria A. Johnson, Erinprit K. Singh, Lidia A. Nazarova, Leslie D. Alexander and Shelli R. McAlpine

Affiliation:

Keywords: Hsp90, Hsp90 inhibitors, macrocycles, client protein, geldanamycin, 17AAG, 17-DMAG, IPI504, clinical trials, cancer, herbimycin radicicol, pochonin, radanamycin, SanA, di-SanA

Abstract: Heat shock proteins (HSP) are a family of highly conserved proteins, whose expression increases in response to stresses that may threaten cell survival. Over the past decade, heat shock protein 90 (Hsp90) has emerged as a potential therapeutic target for cancer as it plays a vital role in normal cell maturation and acts as a molecular chaperone for proper folding, assembly, and stabilization of many oncogenic proteins. To date, a majority of Hsp90 inhibitors that have been discovered are macrocycles. The relatively rigid conformation provided by the macrocyclic scaffold allows for a selective interaction with a biological target such as Hsp90. This review highlights the discovery and development of nine macrocycles that inhibit the function of Hsp90, detailing their potency and the client proteins affected by Hsp90 inhibition.

Cite this article as:

A. Johnson Victoria, K. Singh Erinprit, A. Nazarova Lidia, D. Alexander Leslie and R. McAlpine Shelli, Macrocyclic Inhibitors of Hsp90, Current Topics in Medicinal Chemistry 2010; 10 (14) . https://dx.doi.org/10.2174/156802610792232088