1. Academic Validation
  2. Assessment of chemical coverage of kinome space and its implications for kinase drug discovery

Assessment of chemical coverage of kinome space and its implications for kinase drug discovery

  • J Med Chem. 2008 Dec 25;51(24):7898-914. doi: 10.1021/jm8011036.
Paul Bamborough 1 David Drewry Gavin Harper Gary K Smith Klaus Schneider
Affiliations

Affiliation

  • 1 Molecular Discovery Research, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK. [email protected]
Abstract

More than 500 compounds chosen to represent kinase inhibitor space have been screened against a panel of over 200 protein kinases. Significant results include the identification of hits against new kinases including PIM1 and MPSK1, and the expansion of the inhibition profiles of several literature compounds. A detailed analysis of the data through the use of affinity fingerprints has produced findings with implications for biological target selection, the choice of tool compounds for target validation, and lead discovery and optimization. In a detailed examination of the tyrosine kinases, interesting relationships have been found between targets and compounds. Taken together, these results show how broad cross-profiling can provide important insights to assist kinase drug discovery.

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