【摘 要】
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The p110α,catalytic subunit of PI3Kα,was the primary phosphoinositide 3-kinases (PI3Ks)isoform involved in oncogenic RTK signaling and tumorigenesis.In this study,the three-dimensional quantitative structure-activity relationship (3D-QSAR),molecular docki
【机 构】
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School of Chemical and Environmental Engineering,Shanghai Institute of Technology,Shanghai 201418,Ch
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The p110α,catalytic subunit of PI3Kα,was the primary phosphoinositide 3-kinases (PI3Ks)isoform involved in oncogenic RTK signaling and tumorigenesis.In this study,the three-dimensional quantitative structure-activity relationship (3D-QSAR),molecular docking and molecular dynamics simulation were employed to study the binding mode between 3-phenylsulfonylaminopyridine derivatives and PI3Kα.The stable and reliable 3D-QSAR models were constructed based on the application of the comparative molecular field analysis (CoMFA)model (q2 =0.704,r2 =0.994) and comparative molecular similarity index analysis (CoMSIA) model (q2 =0.804,r2 =0.996).The contour maps illustrated relationship between structure and biological activity.The conformation obtained after MD simulation was more stable than the docked conformation.MD simulation was performed in a more realistic environment,and was much closer to physiological conditions.As a result,five novel PI3Kα inhibitors were designed with better biological activity than the template compound 8.
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