Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372133 | Bioorganic & Medicinal Chemistry Letters | 2011 | 5 Pages |
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.
Graphical abstractA robust virtual screening method has been developed based on the crystal structure (PDB code 2hyy) of Abl-imatinib complex using Surflex-Docking to screen six analogs of imatinib newly synthesized as potential Abl kinase inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide