文献类型：期刊文献

英文题名：Identification of Inhibitors against p90 Ribosomal S6 Kinase 2 (RSK2) through Structure-Based Virtual Screening with the Inhibitor-Constrained Refined Homology Model

作者：Li, Shiliang[1];Zhou, Yi[1];Lu, Weiqiang[1];Zhong, Ye[1];Song, Wenlong[1];Liu, Kangdong[2];Huang, Jin[1];Zhao, Zhenjiang[1];Xu, Yufang[1];Liu, Xiaofeng[1];Li, Honglin[1]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Zhengzhou Univ, Basic Med Coll, Zhengzhou 450001, Peoples R China

年份：2011

卷号：51

期号：11

起止页码：2939

外文期刊名：JOURNAL OF CHEMICAL INFORMATION AND MODELING

收录：;EI(收录号：20114814572164);WOS:【SCI-EXPANDED(收录号:WOS:000297275000016)】；

基金：This work was supported by the National Natural Science Foundation of China (grants 20803022, 21173076, and 81102375), the Shanghai Committee of Science and Technology (grants 09dZ1975700 and 10431902600), the Innovation Program of Shanghai Municipal Education Commission (grant 10ZZ41), the National S&T Major Project of China (grant 2011-ZX09307-002-03), and the Fundamental Research Funds for the Central Universities. H. Li is also sponsored by the Shanghai Rising-Star Program (grant 10QA1401800) and the Program for New Century Excellent Talents in University (grant NCET-10-0378). We also thank Prof. Rolf Hilgenfeld from University of Lubeck for careful reading and polishing of this manuscript.

语种：英文

外文关键词：Virtual reality - Crystal structure - Digital libraries - Amino acids - Binding sites - Diseases

摘要：P90 ribosomal S6 kinase 2 (RSK2), which was shown to be overexpressed in human cancers, is a serine/threonine kinase and a potential target for cancer treatment. RSK2 comprises two terminal kinase domains (NTKD and CTKD) that can be inhibited by binding with different types of inhibitors at the ATP binding sites. In the absence of a crystal structure of RSK2, we constructed a model for the 3D structure of the RSK2 NTKD by homology modeling and stepwise constrained refinement with the reported inhibitors using a molecular docking method. Structure-based virtual screening was subsequently performed against a library containing commercially available compounds using the refined model. This resulted in the identification of seven novel RSK2 inhibitors with IC(50) values ranging from 2.4 to 14.45 mu M.