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

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