Assessment of Chemical Coverage of Kinome Space and Its Implications for Kinase Drug Discovery

被引：136

作者：

Bamborough, Paul ^{[1
]}

Drewry, David ^{[2
]}

Harper, Gavin ^{[1
]}

Smith, Gary K. ^{[2
]}

Schneider, Klaus ^{[3
]}

机构：

[1] GlaxoSmithKline Inc, Mol Discovery Res, Stevenage SG1 2NY, Herts, England

[2] GlaxoSmithKline Inc, Mol Discovery Res, Res Triangle Pk, NC 27709 USA

[3] GlaxoSmithKline Inc, Mol Discovery Res, Harlow CM19 5AW, Essex, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 24期

关键词：

D O I：

10.1021/jm8011036

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

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.

引用

页码：7898 / 7914

页数：17

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