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 journal › Article

34 Citations (Scopus)

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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Molecular Chaperones
Stabilization
Throughput
Proteins

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., ... 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

Barker, JJ, Barker, O, Courtney, SM, Gardiner, M, Hesterkamp, T, Ichihara, O, Mather, O, Montalbetti, CAGN, Müller, A, Varasi, M, Whittaker, M & Yarnold, CJ 2010, 'Discovery of a novel Hsp90 inhibitor by fragment linking', ChemMedChem, vol. 5, no. 10, pp. 1697-1700. https://doi.org/10.1002/cmdc.201000219
Barker JJ, Barker O, Courtney SM, Gardiner M, Hesterkamp T, Ichihara O et al. Discovery of a novel Hsp90 inhibitor by fragment linking. ChemMedChem. 2010 Oct 4;5(10):1697-1700. https://doi.org/10.1002/cmdc.201000219
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. / Discovery of a novel Hsp90 inhibitor by fragment linking. In: ChemMedChem. 2010 ; Vol. 5, No. 10. pp. 1697-1700.
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