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 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

作者机构：Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJi'nan 250117China School of PharmacyJi'nan UniversityGuangzhou 510632China Department of Medicinal ChemistryKey Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJi'nan 250012China Department of ChemistryJiangsu Key Laboratory of Drug Design and OptimizationChina Pharmaceutical UniversityNanjing 211198China Stare Key Laboratory of Biotherapy and Cancer CenterWest China Hospitaland Collaborative Innovation Center of BiotherapySichuan UniversityChengdu 610041China Stare Key Laboratory of Natural MedicinesJiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesChina Pharmaceutical UniversityNanjing 210009China Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of EducationWest China School of PharmacySichuan UniversityChengdu 610041China Key Laboratory of Pesticide&Chemical Biology(CCNU)Ministry of EducationDepartment of ChemistryCentral China Normal UniversityWuhan 430079China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2020年第31卷第7期

页      面：1695-1708页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

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 

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

摘      要：Great success has been witnessed in last decades,some new techniques and strategies have been widely used in drug *** 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 *** 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 *** and emerging methods for virtual target profiling are briefly summarized herein.(C)Research on targeted autophagy to treat diseases has received encouraging ***,due to the complexity of autophagy and disease,experimental and in silico methods should be performed synergistically for the entire *** 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 *** studies demonstrated that HDACs,which possess low deacetylase activities,exhibited more efficient defatty-acylase ***,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