@article {245,
	title = {A fluorescence polarization assay for inhibitors of Hsp90},
	journal = {Analytical Biochemistry},
	volume = {350},
	year = {2006},
	month = {2006/03/15/},
	pages = {202 - 213},
	abstract = {Hsp90 encodes a ubiquitous molecular chaperone protein conserved among species which acts on multiple substrates, many of which are important cell-signaling proteins. Inhibition of Hsp90 function has been promoted as a mechanism to degrade client proteins involved in tumorigenesis and disease progression. Several assays to monitor inhibition of Hsp90 function currently exist but are limited in their use for a drug discovery campaign. Using data from the crystal structure of an initial hit compound, we have developed a fluorescence polarization assay to monitor binding of compounds to the ATP-binding site of Hsp90. This assay is very robust (Z{\textquoteright} > 0.9) and can detect affinity of compounds with IC50s to 40 nM. We have used this assay in conjunction with cocrystal structures of small molecules to drive a structure-based design program aimed at the discovery and optimization of a novel class of potent Hsp90 inhibitors.},
	keywords = {Adenosine Triphosphatases/antagonists \& inhibitors; Binding Sites; Coumarins/chemistry/pharmacology; Crystallography, X-Ray; Fluorescence Polarization/methods; HSP90 Heat-Shock Proteins/antagonists \& inhibitors; Inhibitory Concentration 50; Pyrazoles/chemistry/pharmacology; Resorcinols/chemistry; Saccharomyces cerevisiae/enzymology; Structure-Activity Relationship},
	author = {Howes,R. and Barril, Xavier and Dymock,B. W. and Grant,K. and Northfield,C. J. and Robertson,A. G. and Surgenor,A. and Wayne,J. and Wright,L. and James,K. and Matthews,T. and Cheung,K. M. and McDonald,E. and Workman,P. and Drysdale,M. J.}
}
