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
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DOI：
10.1021/jm8011036
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发表时间：
2008-12-25
影响因子：
7.3
通讯作者：
Schneider, Klaus
中科院分区：
文献类型：
--
作者：
Bamborough, Paul;Drewry, David;Schneider, Klaus
选择代表激酶抑制剂空间的500多种化合物已经针对200多种蛋白激酶的小组进行了筛选。显著的结果包括识别针对新激酶（包括PIM 1和MPSK 1）的命中，以及几种文献化合物的抑制谱的扩展。通过使用亲和指纹对数据进行详细分析，得出了对生物靶标选择、靶标验证工具化合物的选择以及先导化合物发现和优化具有影响的发现。在对酪氨酸激酶的详细研究中，发现了目标和化合物之间的有趣关系。总之，这些结果表明，广泛的交叉分析可以提供重要的见解，以帮助激酶药物的发现。
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.