Radester, a novel inhibitor of the Hsp90 protein folding machinery.

Abstract

[reaction: see text]. The antitumor antibiotics radicicol and geldanamycin are potent inhibitors of the Hsp90 protein folding machinery. Radester is a hybrid composed of radicicol's resorcinol ring and geldanamycin's quinone through an isopropyl ester. Radester was prepared, and the cytotoxicity of it and the corresponding hydroquinone were determined in MCF-7 breast cancer cells to be 13.9 and 7.1 microM, respectively. Protein degradation assays were performed on Hsp90-dependent client proteins, Her-2 and Raf, to correlate Hsp90 inhibition to cytotoxicity.

• Authors: Gang Shen, Brian S J Blagg
• Journal: Organic letters (Org Lett) Vol. 7 Issue 11 Pg. 2157-60 (May 26 2005) ISSN: 1523-7060 [Print] United States
• PMID: 15901158 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Benzene Derivatives
• Benzoquinones
• G3130
• HSP90 Heat-Shock Proteins
• KOSN1559
• Lactams, Macrocyclic
• Phenols
• Pyrazoles
• Quinones
• radester
• geldanamycin

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Benzene Derivatives (chemical synthesis, chemistry, pharmacology)
• Benzoquinones
• Drug Screening Assays, Antitumor
• HSP90 Heat-Shock Proteins (antagonists & inhibitors)
• Humans
• Inhibitory Concentration 50
• Lactams, Macrocyclic
• Oxidation-Reduction
• Phenols (chemistry, pharmacology)
• Pyrazoles (chemistry, pharmacology)
• Quinones (chemistry, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured