Novobiocin has previously been shown to be an inhibitor of Hsp90. In an effort to produce more effective inhibitors of Hsp90, analogues of novobiocin have been prepared. Biological screening for the depletion of Hsp90-dependent client proteins, phospho-AKT, AKT, and HER-2 has led to the identification of a molecule with effective concentrations in the low micromolar range. Structure-activity relationships resulting from these studies have suggested alternative structures that are likely to produce molecules with enhanced activity.

File Number: 2005 FY 03 

Web site: http://www.medchem.ku.edu

Other Information: *State of Development* The molecules described herein represent the first set of new lead compounds for the inhibition of Hsp90. Future studies will be required to determine whether these molecules can be further optimized and whether they behave similarly in cells/animals. Available for licensing.