The Hsp90 chaperone as a promising drug target.
Geldanamycin and radicicol, antibiotics produced by Streptomycetes and fungi, respectively, were originally discovered many years ago. Only recently was it discovered that they bind with high specificity within the ADP/ATP binding pocket of the Hsp90 molecular chaperone, thereby inhibiting the function of Hsp90. In eukaryotic cells Hsp90 catalyzes the final activation step of many of the most important regulatory proteins. Cells that lose this function are severely compromised and cannot progress through the cell cycle. In cell-culture systems, the administration of geldanamycin induces degradation of several signal transduction proteins of oncological importance. Hsp90 inhibitors are, therefore, now attracting considerable attention as potential antitumor agents; one geldanamycin derivative is already in phase I trials as an anticancer drug. These drugs may also have virucidal, antimalarial and ischemia-protective effects.
Piper
P W
PW
Department of Biochemistry and Molecular Biology, University College London, UK. piper@bsm.bioc.ucl.ac.uk
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000138:chemical synthesis; D000935:Antifungal Agents / Q000008:administration & dosage / Q000138:chemical synthesis; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones