Novel, Potent Small-Molecule Inhibitors of the Molecular Chaperone Hsp90 Discovered through Structure-Based Design
| Autor: | Brian Dymock, Roderick E. Hubbard, Paul Brough, Paul Webb, Allan E. Surgenor, Edward McDonald, Paul Workman, Xavier Barril, Stephen D. Roughley, Martin J. Drysdale, Lisa Wright, Julie E. Cansfield, Andrew Massey |
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| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Molecular model Protein Conformation Stereochemistry Glycine Structure-Activity Relationship Adenosine Triphosphate Protein structure Heat shock protein Drug Discovery Humans Structure–activity relationship HSP90 Heat-Shock Proteins Amines Binding site Binding Sites Molecular Structure biology Chemistry Amides Small molecule Hsp90 Biochemistry Drug Design Chaperone (protein) biology.protein Molecular Medicine |
| Zdroj: | Journal of Medicinal Chemistry. 48:4212-4215 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm050355z |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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