New techniques and strategies in drug discovery  

作　　者：Jintong Du Jing Guo Dongwei Kang Zhihong Li Guan Wang Jianbing Wu Zhen Zhang Hao Fang Xuben Hou Zhangjian Huang Guobo Li Xiaoyun Lu Xinyong Liu Liang Ouyang Li Rao Peng Zhan Xiaojin Zhang Yihua Zhang 

机构地区：[1]Shandong Cancer Hospital and Institute,Shandong First Medical University and Shandong Academy of Medical Sciences,Ji'nan 250117,China [2]School of Pharmacy,Ji'nan University,Guangzhou 510632,China [3]Department of Medicinal Chemistry,Key Laboratory of Chemical Biology(Ministry of Education),School of Pharmaceutical Sciences,Shandong University,Ji'nan 250012,China [4]Department of Chemistry,Jiangsu Key Laboratory of Drug Design and Optimization,China Pharmaceutical University,Nanjing 211198,China [5]Stare Key Laboratory of Biotherapy and Cancer Center,West China Hospital,and Collaborative Innovation Center of Biotherapy,Sichuan University,Chengdu 610041,China [6]Stare Key Laboratory of Natural Medicines,Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases,China Pharmaceutical University,Nanjing 210009,China [7]Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education,West China School of Pharmacy,Sichuan University,Chengdu 610041,China [8]Key Laboratory of Pesticide&Chemical Biology(CCNU),Ministry of Education,Department of Chemistry,Central China Normal University,Wuhan 430079,China

出　　处：《Chinese Chemical Letters》2020年第7期1695-1708,共14页中国化学快报（英文版）

基　　金：This work was supported by grants from the National Natural Science Foundation of China(Nos.81973173 and 81773571),Jiangsu Province Funds for Excellent Young Scientists(No.BK20170088),the Six Talent Peaks Project(No.YY-023)and the 333 Project of Jiangsu Province.

摘　　要：Great success has been witnessed in last decades,some new techniques and strategies have been widely used in drug discovery.In this roadmap,several representative techniques and strategies are highlighted to show recent advances in this filed.(A)A DOX protocol has been developed for accurate protein-ligand binding structure prediction,in which first principle method was used to rank the binding poses.Validation against crystal structures have found that DOX prediction achieved an impressive success rate of 99%,indicating significant improvement over molecular docking method.(B)Virtual target profiling is a compound-centric strategy enabling a parallel implementation of interrogating compounds against various targets in a single screen,which has been used in hit/lead identification,drug repositioning,and mechanism-of-action studies.Current and emerging methods for virtual target profiling are briefly summarized herein.(C)Research on targeted autophagy to treat diseases has received encouraging progress.However,due to the complexity of autophagy and disease,experimental and in silico methods should be performed synergistically for the entire process.This part focuses on in silico methods in autophagy research to promote their use in medicinal research.(D)Histone deacetylases(HDACs)play important roles in various biological functions through the deacetylation of lysine residues.Recent studies demonstrated that HDACs,which possess low deacetylase activities,exhibited more efficient defatty-acylase activities.Here,we review the defatty-acylase activity of HDACs and describe examples for the design of isoform selective HDAC inhibitor.(E)The FDA approval of three kinase allosteric inhibitors and some others entering clinical study has spurred considerable interests in this targeted drug discovery area.(F)Recent advances are reviewed in structure-based design of novel antiviral agents to combat drug resistance.(G)Since nitric oxide(NO)exerts anticancer activity depending on its concentration,optimal levels of NO in cance

关 键 词：Protein-ligand binding structure Target profiling In silico autophagy method Defatty-acylase Allosteric kinase inhibitor Drug resistance Nitric oxide donor Photoactivation strategies 

分 类 号：TQ460.1[化学工程—制药化工]