检索结果-南通市图书馆

Chinese Journal of Structural Chemistry 2017年第12期36卷 1975-1986页

作者：刘蒙蒙王必武汪斌李静舒茂张娅林治华 College of Pharmacy and Bioengineering Chongqing University of Technology College of Chemistry and Chemical Engineering Chongqing University

Tyrosine protein kinase JAK3 has a very important significance on organ transplantation and the treatment of autoimmune diseases, which has been a potential therapeutic target. In recent years, a large number of JAK3 inhibitors have been reported. However, the poor selectivity and side effects have limited their widespread use in clinical practice. In order to solve this problem, 52 potential small-molecule inhibitors were combined with JAK1, JAK2 and JAK3 respectively to obtain the optimal conformation of small molecules. On the basis of that we established 3D quantitative structure-activity relationships（3D-QSAR） model. Comparative molecular field analysis（Co MFA） and molecular similarity analysis（Co MSIA） were used to evaluate the model. We took advantage of reverse docking to explore the underlying toxicity and side effects. Combining 3D quantitative structure-activity relationships, surflex-dock and reverse docking results, ten 5 H-pyrrolo[2,3-b]pyrazine-2-phenyl ether derivatives based on the most optimal selectivity and activity compound 39 were designed. It can be seen from Co MFA and Co MSIA predicted active values of designed molecules that the selectivity of designed small molecules was improved obviously. Among them, compounds 61 and 62 could become the potential small molecule compounds.

关键词： JAK3 inhibitors 3D-QSAR surflex-doek reverse docking selectivity

Evaluating reverse docking on general and selective inhibitors: a case study about glide

在线全文

学校读者我要写书评

暂无评论

Journal of Chinese Pharmaceutical Sciences 2020年第10期29卷 679-688页

作者： Mingna Li Xing Wu Liangren Zhang Zhenming Liu State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China Hengdian Group Holdings Limited Hangzhou 310007China

As a powerful tool for target prediction,reverse docking remains largely *** objective evaluation of reverse docking software can help us know better about the strength and weakness of these tools,hence guiding us in target *** the present study,we evaluated the target prediction power of Glide(SP)against general inhibitors and selective *** results showed that the scoring tendency could be different for each ligand,and overall scoring sampling was necessary for a better understanding of the docking score for a certain protein-ligand ***,the input conformation of the binding pocket could affect the docking ***(SP)showed a preferable performance on the target prediction of the general ***,the accuracy of the target prediction of the selective inhibitors was relatively low,indicating that Glide(SP)might not be capable for this *** case study about COVID-19 proved that coagulation factor Xa might be a potential target of ***,we recommend the further development of reverse docking tools and rectification of inter-target scoring bias.

关键词： reverse docking Target prediction Software evaluation

Exploration of the mechanisms of Aflatoxin B1 toxicity and the targets of Oltipraz by reverse docking

在线全文

学校读者我要写书评

暂无评论

Journal of Chinese Pharmaceutical Sciences 2014年第3期23卷 182-185页

作者：张裕郭丽梅北京大学医学部基础医学院病理学系北京100191

Aflatoxin B1 toxicity is well known but the mechanism of this toxicity is still unclear. In addition, the target of the anti-aflatoxin chemopreventive drug Oltipraz remains to be identified. In this study, we employed computer aided reverse docking analysis to identify putative targets of Aflatoxin B1（AFB） and Oltipraz. The results showed that the clinically known toxic effects of AFB are related to this molecule＇s strong binding affinity for key proteins involved in cell apoptosis, hormone metabolism, immune suppression, and digestive organ function. In addition, virtual binding assay indicated that Oltipraz neutralizes the toxicity of AFB by inhibiting its biotransformation enzymes. In conclusion, the technique of reverse docking may be used to identify the specific targets of AFB and Oltipraz, and our findings could significantly accelerate the mechanistic studies of the two molecules and provide guidance for the development of anti-AFB drugs.

关键词： reverse docking Aflatoxin B1 Oltipraz

Bufotenine and its derivatives:synthesis,analgesic effects identification and computational target prediction

在线全文

学校读者我要写书评

暂无评论

Chinese Journal of Natural Medicines 2021年第6期19卷 454-463页

作者： ZHAO Chao CHEN Min SUN Shan-Liang WANG Jiao-Jiao ZHONG Yue CHEN Huan-Huan LI He-Min XU Han LI Nian-Guang MA Hong-Yue WANG Xiao-Long National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources IndustrializationJiangsu Key Laboratory for High Technology Research of TCM FormulaeNanjing University of Chinese MedicineNanjing 210023China

Natural product bufotenine(5)which could be isolated from Venenum Bufonis,has been widely used as a tool in central nervous system(CNS)*** present here its quaternary ammonium salt(6)which was synthesized with high yields using 5-benzyloxyindole as raw materials,and we firstly discover its analgesic effects in *** analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in ***,the combination of compound 6 and morphine has a synergistic *** intended to explain the molecular mechanism of this ***,36 analgesic-related targets(including 15 G protein-coupled receptors,6 enzymes,13 ion channels,and 2 others)were systemically evaluated using reverse *** results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase(AChE)orα_(4)β_(2) nicotinic acetylcholine receptor(nAChR).This study provides practitioners a new insight of analgesic effects.

关键词： Bufotenine Analgesic reverse docking Target prediction Binding mode

Exploring the Pathways and Targets of Shexiang Baoxin Pill for Coronary Heart Disease through a Network Pharmacology Approach

在线全文

学校读者我要写书评

暂无评论

World Journal of Traditional Chinese Medicine 2018年第4期4卷 137-181页

作者： Shou-De Zhang Zhan-Hai Su Rui-Hui Liu Yan-Yan Diao Shi-Liang Li Ya-Ping-Hua Hong-Lin Li Wei-Dong Zhang State Key Laboratory of Plateau Ecology and Agriculture Qinghai UniversityXiningQinghai Department of Phytochemistry School of PharmacySecond Military Medical University Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science and TechnologyShanghaiChina Department of Clinical Science 2 Faculty of Medicine and DentistryUniversity of Bergen5009Norway

Objective: To investigate the network pharmacology of Shexiang Baoxin pill(SBP) and systematically analyze the mechanisms of ***: In this study, we excavated all the targets of 26 constituents of SBP which were identified in rat plasma though literature mining and target calculation(reverse docking and similarity search) and analyzed the multiple pharmacology actions of SBP comprehensively through a network pharmacology ***: In the end, a total of 330 Homo sapiens targets were identified for 26 blood constituents of ***, the pathway enrichment analysis found that these targets mapped into 171 KEGG pathways and 31 of which were more *** these identified pathways, 3 pathways were selected for analyzing the mechanisms of SBP for treating coronary heart ***: This study systematically illustrated the mechanisms of the SBP by analyzing the corresponding "drug-target-pathway-disease" interaction network.

关键词： Coronary heart disease network pharmacology reverse docking Shexiang Baoxin pill similarity search