The CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
Bioorg Med Chem Lett. 2011 Dec 1;21(23):6964-8. doi: 10.1016/j.bmcl.2011.09.127. Epub 2011 Oct 7.
Six analogs of imatinib, an Abl kinase inhibitor clinically used as a first-line therapeutic agent for chronic myeloid leukaemia (CML), have been synthesized and characterized. And their potency as Abl kinase inhibitors have been screened by a robust virtual screening method developed based on the crystal structure (PDB code 2hyy) of Abl-imatinib complex using Surflex-Docking. The docking results are consistent with the inhibitory potency of the compounds characterized by MS method. And the H-bonds between imatinib analogs and Thr315 and Met318 residues in Abl kinase are shown to be crucial for achieving accurate poses and high binding affinities for the ATP-competitive kinase inhibitors.
已合成并表征了 6 种伊马替尼类似物，伊马替尼是一种临床上用作慢性髓性白血病 (CML) 一线治疗药物的 Abl 激酶抑制剂。并且，使用基于 Abl-伊马替尼复合物晶体结构（PDB 代码 2hyy）开发的强大虚拟筛选方法，通过 MS 方法对化合物的抑制能力进行了筛选。对接结果与化合物的抑制能力一致。而且，伊马替尼类似物与 Abl 激酶中的 Thr315 和 Met318 残基之间的氢键对于获得准确的构象和对 ATP 竞争型激酶抑制剂的高结合亲和力至关重要。
