Victoria A. Johnson, Erinprit K. Singh, Lidia A. Nazarova, Leslie D. Alexander and Shelli R. McAlpine Pages 1380 - 1402 ( 23 )
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.
Hsp90, Hsp90 inhibitors, macrocycles, client protein, geldanamycin, 17AAG, 17-DMAG, IPI504, clinical trials, cancer, herbimycin radicicol, pochonin, radanamycin, SanA, di-SanA
Department of Chemistry and Biochemistry, 5500 Campanile Drive, San Diego State University, San Diego, CA 92182-1030.