Discovery of a novel Hsp90 inhibitor by fragment linking

John J. Barker; Oliver Barker; Stephen M. Courtney; Mihaly Gardiner; Thomas Hesterkamp; Osamu Ichihara; Owen Mather; Christian A G N Montalbetti; Annett Müller; Mario Varasi; Mark Whittaker; Christopher J. Yarnold

doi:10.1002/cmdc.201000219

Discovery of a novel Hsp90 inhibitor by fragment linking

John J. Barker, Oliver Barker, Stephen M. Courtney, Mihaly Gardiner, Thomas Hesterkamp, Osamu Ichihara, Owen Mather, Christian A G N Montalbetti, Annett Müller, Mario Varasi, Mark Whittaker, Christopher J. Yarnold

Istituto Europeo di Oncologia

Research output: Contribution to journal › Article

Abstract

Hooking up! Hsp90 is a molecular chaperone involved in the stabilisation of numerous client proteins including those involved in oncogenic transformations. Through a high-throughput biochemical fragment screen, we have identified novel fragment inhibitors of Hsp90. Two fragment hits were combined to give a dual-fragment Hsp90 complex, and the following successful fragment-linking resulted in a 1000-fold improvement in activity. (Chemical Equation Presented).

Original language	English
Pages (from-to)	1697-1700
Number of pages	4
Journal	ChemMedChem
Volume	5
Issue number	10
DOIs	https://doi.org/10.1002/cmdc.201000219
Publication status	Published - Oct 4 2010

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Keywords

Fragment linking
Fragment-based screening
Heat shock protein 90
Hsp90
Structure-based drug design

ASJC Scopus subject areas

Pharmacology, Toxicology and Pharmaceutics(all)
Organic Chemistry
Molecular Medicine

Cite this

Barker, J. J., Barker, O., Courtney, S. M., Gardiner, M., Hesterkamp, T., Ichihara, O., Mather, O., Montalbetti, C. A. G. N., Müller, A., Varasi, M., Whittaker, M., & Yarnold, C. J. (2010). Discovery of a novel Hsp90 inhibitor by fragment linking. ChemMedChem, 5(10), 1697-1700. https://doi.org/10.1002/cmdc.201000219

Discovery of a novel Hsp90 inhibitor by fragment linking. / Barker, John J.; Barker, Oliver; Courtney, Stephen M.; Gardiner, Mihaly; Hesterkamp, Thomas; Ichihara, Osamu; Mather, Owen; Montalbetti, Christian A G N; Müller, Annett; Varasi, Mario; Whittaker, Mark; Yarnold, Christopher J.

In: ChemMedChem, Vol. 5, No. 10, 04.10.2010, p. 1697-1700.

Research output: Contribution to journal › Article

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Access to Document

10.1002/cmdc.201000219