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Medicinal Chemistry
ISSN (Print): 1573-4064
ISSN (Online): 1875-6638
Epub Full Text Article
DOI: 10.2174/1573406409666131128143601      Price:  $95









Discovery of Novel CK2 Leads by Cross-Docking Based Virtual Screening

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Author(s): Haopeng Sun, Xiaowen Wu, Xiaoli Xu, Zhengyu Jiang, Zongliang Liu and Qidong You
Abstract:
Protein kinase CK2, a serine/threonine kinase, is an attractive therapeutic target for many diseases. Here we describe an application of cross-docking based drug design to discover novel and potent CK2 leads. Glide SP was chosen as the most suitable docking approach by comparing four docking protocols through native-docking. Then twenty-four CK2 crystal structures were compared by recovering known active ligands from a decoy database to select the optimal ensemble of CK2 structures, 2PVN, 2ZJW, 3AMY, 3FL5 and 3KXH were severed as the assemble, which were used in the virtual screening of compiled SPECS database for small molecules inhibiting CK2. Seven compounds were selected and purchased to test the biological activity. Compound g (AQ-390/42425635) showed the best inhibition rate and the lowest IC50, which can be used as a lead for our subsequent optimization
Keywords:
Protein kinase CK2 inhibitor, Cross-docking, Receptor-based virtual screening, Biological test, Lead
Affiliation:
China Pharmaceutical University, 24 Tong Jia Xiang Road, Nanjing, China