کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
444391 692973 2012 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of CK2 inhibitors with new scaffolds by a hybrid virtual screening approach based on Bayesian model; pharmacophore hypothesis and molecular docking
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی تئوریک و عملی
پیش نمایش صفحه اول مقاله
Identification of CK2 inhibitors with new scaffolds by a hybrid virtual screening approach based on Bayesian model; pharmacophore hypothesis and molecular docking
چکیده انگلیسی

Protein kinase casein kinase 2 (CK2), a member of the serine/threonine kinase family, has been established as one of the most attractive targets for molecularly targeted cancer therapy. The discovery of CK2 inhibitors has thus attracted much attention in recent years. In this investigation, a hybrid virtual screening approach based on Bayesian classification model, pharmacophore hypothesis and molecular docking was proposed and employed to identify CK2 inhibitors. We first established a naïve Bayes classification model of CK2 inhibitors/non-inhibitors and pharmacophore hypotheses of CK2 inhibitors. The docking parameters and scoring functions were also optimized in advance. The three virtual screening methods were sequentially used to screen two large chemical libraries, Specs and Enamine, for retrieving new CK2 inhibitors. Finally 30 compounds were selected from the final hits for in vitro CK2 kinase inhibitory assays. Five compounds with completely novel scaffolds showed a good inhibitory potency against CK2, which have good potentials for a future hit-to-lead optimization.

A hybrid virtual screening protocol based on Bayesian model, pharmacophore hypothesis and molecular docking was employed to identify novel CK2 inhibitors and five compounds with new scaffolds were discovered.Figure optionsDownload high-quality image (112 K)Download as PowerPoint slideHighlights
► A naïve Bayes classification model of CK2 inhibitors/non-inhibitors was developed.
► A hybrid protocol was proposed and applied to identify novel CK2 inhibitors.
► Five new CK2 inhibitors with novel scaffolds were identified.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Graphics and Modelling - Volume 36, June 2012, Pages 42–47
نویسندگان
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