Emerging Hsp90 inhibitors: from discovery to clinic.
Hsp90 is a chaperone with important roles in maintaining transformation and in elevating the survival and growth potential of cancer cells. Activation of signaling pathways mediated by Hsp90 protein clients is necessary for cell proliferation, regulation of cell cycle progression and apoptosis. Additionally, gain-of-function mutations responsible for transformation often require Hsp90 for the maintenance of their folded, functionally active conformations. These characteristics promise Hsp90 as an important target in cancer therapy and prompt for the identification, development and clinical translation of small molecule inhibitors of the chaperone. This review intends to update the reader on the status of several existing and emerging classes of direct inhibitors of Hsp90 ATPase activity.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA. chiosisg@mskcc.org
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D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000145:classification / Q000494:pharmacology; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding
D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases