Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Republic of Korea.
Bioorg Med Chem Lett. 2011 Apr 1;21(7):2021-4. doi: 10.1016/j.bmcl.2011.02.015. Epub 2011 Feb 26.
Phosphoinositide 3-kinase alpha (PI3Kα) has proved to be an attractive target for the development of therapeutics for the treatment of cancer. Herein we report a successful application of the structure-based virtual screening to identify the novel inhibitors of PI3Kα. These inhibitors have desirable physicochemical properties as a drug candidate and reveal a moderate potency with IC(50) values ranging from 20 to 40 μM. Therefore, they deserve a consideration for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of PI3Kα are addressed in detail.
磷酸肌醇 3-激酶α（PI3Kα）已被证明是开发癌症治疗药物的一个有吸引力的靶点。本文报告了基于结构的虚拟筛选在鉴定 PI3Kα新型抑制剂方面的成功应用。这些抑制剂具有作为候选药物的理想理化性质，其抑制活性适中，IC（50）值在 20 到 40μM 之间。因此，它们值得通过构效关系（SAR）研究进一步开发，以优化抑制活性。详细讨论了与新鉴定的抑制剂在 PI3Kα的 ATP 结合位点中稳定相关的结构特征。
