Macrocyclic inhibitors of hsp90

• Published in: Current topics in medicinal chemistry Vol. 10; no. 14; p. 1380
• Main Authors: Johnson, Victoria A, Singh, Erinprit K, Nazarova, Lidia A, Alexander, Leslie D, McAlpine, Shelli R
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01-10-2010
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; HSP90 Heat-Shock Proteins - antagonists & inhibitors; Humans; Lactams, Macrocyclic - chemistry; Lactams, Macrocyclic - therapeutic use; Molecular Chaperones - antagonists & inhibitors; Molecular Chaperones - chemistry; Neoplasms - drug therapy; Signal Transduction
• ISSN: 1873-4294
• DOI: 10.2174/156802610792232088

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.