2cdd
From Proteopedia
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==Overview== | ==Overview== | ||
| - | 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' > 0.9) and can detect affinity of compounds with IC50s to 40, nM. We have used this assay in conjunction with cocrystal structures of, . | + | 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' > 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2CDD is a | + | 2CDD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CT5 as [http://en.wikipedia.org/wiki/ligand ligand]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CDD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: pyrazole]] | [[Category: pyrazole]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 13:37:27 2007'' |
Revision as of 11:32, 5 November 2007
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HUMAN HSP90 WITH 4-(4-(2,3-DIHYDRO-BENZOL(1,4)DIOXIN-6-YL)-5-METHYL-1H-PYRAZOL-3-YL)-6-ETHYL-BENZENE-1,3-DIOL
Overview
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' > 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.
About this Structure
2CDD is a Single protein structure of sequence from Homo sapiens with CT5 as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.
Reference
A fluorescence polarization assay for inhibitors of Hsp90., Howes R, Barril X, Dymock BW, Grant K, Northfield CJ, Robertson AG, Surgenor A, Wayne J, Wright L, James K, Matthews T, Cheung KM, McDonald E, Workman P, Drysdale MJ, Anal Biochem. 2006 Mar 15;350(2):202-13. Epub 2006 Jan 23. PMID:16460658
Page seeded by OCA on Mon Nov 5 13:37:27 2007
Categories: Homo sapiens | Single protein | Barril, X. | Cheung, K.M. | Drysdale, M.J. | Dymock, B.W. | Grant, K. | Howes, R. | James, K. | Matthews, T. | Mcdonald, E. | Northfield, C.J. | Robertson, A. | Surgenor, A. | Wayne, J. | Workman, P. | Wright, L. | CT5 | Atp-binding | Atpase | Chaperone | Heat shock | Hsp90 | Nucleotide-binding | Phosphorylation | Pyrazole
