Fragment based discovery of a novel and selective PI3 kinase inhibitor
Fragment based discovery of a novel and selective PI3 kinase inhibitor
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DOI：
10.1016/j.bmcl.2011.07.117
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发表时间：
2011-11-01
影响因子：
2.7
通讯作者：
Brown, David G.
中科院分区：
文献类型：
--
作者：
Hughes, Samantha J.;Millan, David S.;Brown, David G.
我们报告了使用片段筛选和基于片段的药物设计来开发 PI3 γ 激酶片段命中的先导化合物。通过高浓度生化筛选发现初始片段命中，然后进行一轮虚拟筛选以识别其他配体有效片段。使用结构引导片段生长和合并策略将它们开发成有效且配体有效的先导化合物。这产生了一种有效的、选择性的、细胞渗透性的 PI3 γ 激酶抑制剂，具有良好的代谢稳定性，可用作临床前工具化合物。 (C) 2011 年，爱思唯尔有限公司出版。
We report the use of fragment screening and fragment based drug design to develop a PI3 gamma kinase fragment hit into a lead. Initial fragment hits were discovered by high concentration biochemical screening, followed by a round of virtual screening to identify additional ligand efficient fragments. These were developed into potent and ligand efficient lead compounds using structure guided fragment growing and merging strategies. This led to a potent, selective, and cell permeable PI3 gamma kinase inhibitor with good metabolic stability that was useful as a preclinical tool compound. (C) 2011 Published by Elsevier Ltd.