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2bsm

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==Overview==
==Overview==
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The crystal structure of a previously reported screening hit 1 (CCT018159), bound to the N terminal domain of molecular chaperone Hsp90 has been used, to design 5-amide analogues. These exhibit enhanced potency against the, target in binding and functional assays with accompanying appropriate, cellular pharmacodynamic changes. Compound 11 (VER-49009) compares, favorably with the clinically evaluated 17-AAG.
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The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues. These exhibit enhanced potency against the target in binding and functional assays with accompanying appropriate cellular pharmacodynamic changes. Compound 11 (VER-49009) compares favorably with the clinically evaluated 17-AAG.
==About this Structure==
==About this Structure==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Barril, X.]]
[[Category: Barril, X.]]
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[[Category: Brough, P.A.]]
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[[Category: Brough, P A.]]
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[[Category: Cansfield, J.E.]]
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[[Category: Cansfield, J E.]]
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[[Category: Drysdale, M.J.]]
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[[Category: Drysdale, M J.]]
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[[Category: Dymock, B.W.]]
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[[Category: Dymock, B W.]]
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[[Category: Hubbard, R.E.]]
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[[Category: Hubbard, R E.]]
[[Category: Massey, A.]]
[[Category: Massey, A.]]
[[Category: Mcdonald, E.]]
[[Category: Mcdonald, E.]]
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[[Category: Roughley, S.D.]]
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[[Category: Roughley, S D.]]
[[Category: Surgenor, A.]]
[[Category: Surgenor, A.]]
[[Category: Webb, P.]]
[[Category: Webb, P.]]
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[[Category: pu3]]
[[Category: pu3]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:27:27 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:41:12 2008''

Revision as of 14:41, 21 February 2008


2bsm, resolution 2.05Å

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NOVEL, POTENT SMALL MOLECULE INHIBITORS OF THE MOLECULAR CHAPERONE HSP90 DISCOVERED THROUGH STRUCTURE-BASED DESIGN

Overview

The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues. These exhibit enhanced potency against the target in binding and functional assays with accompanying appropriate cellular pharmacodynamic changes. Compound 11 (VER-49009) compares favorably with the clinically evaluated 17-AAG.

About this Structure

2BSM is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design., Dymock BW, Barril X, Brough PA, Cansfield JE, Massey A, McDonald E, Hubbard RE, Surgenor A, Roughley SD, Webb P, Workman P, Wright L, Drysdale MJ, J Med Chem. 2005 Jun 30;48(13):4212-5. PMID:15974572

Page seeded by OCA on Thu Feb 21 16:41:12 2008

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