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CCLab-a multi-objective genetic algorithm based combinatorial library design software and an application for histone deacetylase inhibitor design

文献类型：期刊论文

作者Fang, Guanghua1; Xue, Mengzhu1; Su, Mingbo2; Hu, Dingyu1; Li, Yanlian1; Xiong, Bing1; Ma, Lanping1; Meng, Tao1; Chen, Yuelei1; Li, Jingya2
刊名BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
出版日期2012-07-15
卷号22期号:14页码:4540-4545
关键词Combinatorial library design Multi-objective optimization Histone deactetylase Inhibitor
ISSN号0960-894X
DOI10.1016/j.bmcl.2012.05.123
文献子类Article
英文摘要The introduction of the multi-objective optimization has dramatically changed the virtual combinatorial library design, which can consider many objectives simultaneously, such as synthesis cost and drug-likeness, thus may increase positive rates of biological active compounds. Here we described a software called CCLab (Combinatorial Chemistry Laboratory) for combinatorial library design based on the multi-objective genetic algorithm. Tests of the convergence ability and the ratio to re-take the building blocks in the reference library were conducted to assess the software in silico, and then it was applied to a real case of designing a 5 x 6 HDAC inhibitor library. Sixteen compounds in the resulted library were synthesized, and the histone deactetylase (HDAC) enzymatic assays proved that 14 compounds showed inhibitory ratios more than 50% against tested 3 HDAC enzymes at concentration of 20 mu g/mL, with IC50 values of 3 compounds comparable to SAHA. These results demonstrated that the CCLab software could enhance the hit rates of the designed library and would be beneficial for medicinal chemists to design focused library in drug development (the software can be downloaded at: http://202.127.30.184:8080/drugdesign.html). (C) 2012 Elsevier Ltd. All rights reserved.
WOS关键词MOLECULAR DIVERSITY ; CHEMISTRY ; DISCOVERY ; OPTIMIZATION
资助项目State Key Laboratory of Drug Research[00000000] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2009ZX09501-010] ; Chinese Academy of Sciences[KSCX2-EW-Q-3-01] ; National Natural Science Foundation of China[81072580] ; National Natural Science Foundation of China[81102306]
WOS研究方向Pharmacology & Pharmacy ; Chemistry
语种英语
WOS记录号WOS:000306101300009
出版者PERGAMON-ELSEVIER SCIENCE LTD
源URL[http://119.78.100.183/handle/2S10ELR8/278014]  
专题药物化学研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
国家新药筛选中心
通讯作者Xiong, Bing
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
2.Natl Drug Screening Ctr, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Fang, Guanghua,Xue, Mengzhu,Su, Mingbo,et al. CCLab-a multi-objective genetic algorithm based combinatorial library design software and an application for histone deacetylase inhibitor design[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2012,22(14):4540-4545.
APA Fang, Guanghua.,Xue, Mengzhu.,Su, Mingbo.,Hu, Dingyu.,Li, Yanlian.,...&Shen, Jingkang.(2012).CCLab-a multi-objective genetic algorithm based combinatorial library design software and an application for histone deacetylase inhibitor design.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,22(14),4540-4545.
MLA Fang, Guanghua,et al."CCLab-a multi-objective genetic algorithm based combinatorial library design software and an application for histone deacetylase inhibitor design".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 22.14(2012):4540-4545.

入库方式： OAI收割

来源：上海药物研究所

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