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 › peer-review

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

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

Access to Document

10.1002/cmdc.201000219

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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 › peer-review

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AU - Mather, Owen

AU - Montalbetti, Christian A G N

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