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

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1697-1700
Number of pages4
JournalChemMedChem
Volume5
Issue number10
DOIs
Publication statusPublished - 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