Bamborough Paul, Drewry David, Harper Gavin, Smith Gary K, Schneider Klaus
Molecular Discovery Research, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
J Med Chem. 2008 Dec 25;51(24):7898-914. doi: 10.1021/jm8011036.
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.
超过500种用于代表激酶抑制剂空间的化合物已针对一组超过200种蛋白激酶进行了筛选。重要结果包括鉴定出针对新激酶（如PIM1和MPSK1）的活性化合物，以及拓展了几种文献报道化合物的抑制谱。通过使用亲和力指纹对数据进行详细分析，得出了对生物靶点选择、用于靶点验证的工具化合物选择以及先导化合物发现与优化具有启示意义的结果。在对酪氨酸激酶的详细研究中，发现了靶点与化合物之间有趣的关系。综合来看，这些结果表明广泛的交叉分析如何能够提供重要见解以助力激酶药物发现。
