Pharmacophore modelling and virtual screening for identification of new Aurora-A kinase inhibitors

Chemical Biology & Drug Design
Xiao-Qiang DengSheng-Yong Yang

Abstract

Aurora-A has been identified as one of the most attractive targets for cancer therapy and a considerable number of Aurora-A inhibitors have been reported recently. In order to clarify the essential structure-activity relationship for the known Aurora-A inhibitors as well as identify new lead compounds against Aurora-A, 3D pharmacophore models were developed based on the known inhibitors. The best hypothesis, Hypo1, was used to screen molecular structural databases, including Specs and China Natural Products Database for potential lead compounds. The hit compounds were subsequently subjected to filtering by Lipinski's rules and docking study to refine the retrieved hits and as a result to reduce the rate of false positive. Finally, 39 compounds were purchased for further in vitro assay against several human tumour cell lines including A549, MCF-7, HepG2 and PC-3, in which Aurora-A is overexpressed. Two compounds show very low micromolar inhibition potency against some of these tumour cells. And they have been selected for further investigation.

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Citations

Mar 1, 2010·Expert Opinion on Drug Discovery·Kyun-Hwan KimBaik-Lin Seong
Jan 21, 2009·Chemical Biology & Drug Design·Hui-Yuan WangSheng-Yong Yang
Nov 3, 2010·Chemical Biology & Drug Design·Jin QinXiaojun Yao
Dec 17, 2016·Bioorganic & Medicinal Chemistry Letters·Michelle van RensburgDavid Barker
May 1, 2014·Molecular Informatics·Mohammad Neaz Morshed
Jul 3, 2009·Chemical & Pharmaceutical Bulletin·Jin-Juan ChenSheng-Yong Yang
May 16, 2009·Expert Opinion on Therapeutic Patents·Mohane Selvaraj CoumarHsing-Pang Hsieh
Sep 14, 2012·SAR and QSAR in Environmental Research·Y LengY D Chen
Jun 20, 2019·Acta Pharmacologica Sinica·Min LiBao-Xue Yang
Dec 15, 2020·Investigational New Drugs·Mohamed E M SaeedThomas Efferth
Jan 15, 2009·Journal of Medicinal Chemistry·Mohane Selvaraj CoumarHsing-Pang Hsieh
Jun 12, 2017·Trends in Pharmacological Sciences·Arun Prasath DamodaranClaude Prigent

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