Lead Generation, AstraZeneca R&D Mölndal, Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
Bioorg Med Chem Lett. 2011 Jan 15;21(2):829-35. doi: 10.1016/j.bmcl.2010.11.087. Epub 2010 Nov 24.
The discovery of ligand efficient and lipophilicity efficient fragment inhibitors of class 1 phosphatidylinositide 3-kinases (PI3K) is reported. A fragment version of the AstraZeneca compound bank was docked to a homology model of the PI3K p110β isoform. Interaction-based scoring of the predicted binding poses served to further prioritise the virtual fragment hits. Experimental screening confirmed potency for a total of 18 fragment inhibitors, belonging to five different structural classes.
报告了一类 1 型磷酸肌醇 3-激酶（PI3K）的配体高效和脂溶性高效片段抑制剂的发现。将阿斯利康化合物库的片段版本对接至 PI3K p110β 同工型的同源模型。基于相互作用的预测结合构象的评分进一步优先考虑虚拟片段命中。实验筛选证实了总共 18 种片段抑制剂的效力，它们属于五个不同的结构类别。
