Novel, Potent Small-Molecule Inhibitors of the Molecular Chaperone Hsp90 Discovered through Structure-Based Design
Journal of Medicinal Chemistry2005Vol. 48(13), pp. 4212–4215
Citations Over TimeTop 10% of 2005 papers
Brian Dymock, Xavier Barril, Paul A. Brough, Julie E. Cansfield, Andrew J. Massey, Edward McDonald, Roderick E. Hubbard, A.E. Surgenor, Stephen D. Roughley, Paul Webb, Paul Workman, Lisa Wright, Martin J. Drysdale
Abstract
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.
Related Papers
- → Integration of the accelerator Aha1 in the Hsp90 co-chaperone cycle(2013)127 cited
- → The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding(2016)76 cited
- → A novel chaperone-activity-reducing mechanism of the 90-kDa molecular chaperone HSP90(1999)77 cited
- → Inhibition of GR‐mediated transcription by p23 requires interaction with Hsp90(2004)46 cited
- → Evidence for chaperone heterocomplexes containing both Hsp90 and VCP(2005)16 cited