In Silico Design of Potent EGFR Kinase Inhibitors using Combinatorial Libraries

Nandi, Sisir and Bagchi, Manish C (2011) In Silico Design of Potent EGFR Kinase Inhibitors using Combinatorial Libraries. Molecular Simulation, 37 (3). pp. 196-209. ISSN 0892-7022

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    Abstract

    This paper is an attempt to design 4-anilinoquinazoline compounds having promising anticancer activities against epidermal growth factor (EGFR) kinase inhibition, using virtual combinatorial library approach. Partial least squares method has been applied for the development of a quantitative structure–activity relationship (QSAR) model based on training and test set approaches. The partial least squares model showed some interesting results in terms of internal and external predictability against EGFR kinase inhibition for such type of anilinoquinazoline derivatives. In virtual screening study, out of 4860 compounds in chemical library, 158 compounds were screened and finally, 10 compounds were selected as promising EGFR kinase inhibitors based on their predicted activities from the QSAR model. These derivatives were subjected to molecular docking study to investigate the mode of binding with the EGFR kinase, and the two compounds (ID 3639 and 3399) showing similar type of docking score and binding patterns with that of the existing drug molecules like erlotinib were finally reported.

    Item Type: Article
    URI: http://www.eprints.iicb.res.in/id/eprint/1311
    Subjects: Structural Biology & Bioinformatics
    Divisions: Indian Institute of Chemical Biology
    Depositing User: Ms Sutapa Ganguly
    Date Deposited: 25 Jan 2012 11:25
    Last Modified: 25 Jan 2012 11:25
    Official URL: http://dx.doi.org/10.1080/08927022.2010.536542
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