Synthesis and docking study of 2-phenylaminopyrimidine Abl tyrosine kinase inhibitors |
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Authors: | Lü Shuang Luo Qun Hao Xiang Li Xianchan Ji Liyun Zheng Wei Wang Fuyi |
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Institution: | 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. |
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Abstract: | 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. |
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Keywords: | Abl kinase Imatinib analogs Synthesis Docking analysis Virtual screening |
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