检索结果-南通市图书馆

Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第2期14卷 517-532页

作者： Shuang Xiang xiaoyun lu International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education(MOE) Guangdong Provincial Key Laboratory of New Drug Design and EvaluationGuangzhou City Key Laboratory of Precision Chemical Drug DevelopmentSchool of PharmacyJinan UniversityGuangzhou 510632China

Neurotrophic receptor kinase(NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors,and tropomyosin receptor kinase(TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these ***,two generations TRK inhibitors have been *** representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target ***,xDFG(TRKAG667C/A/S,homologous TRKCG696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib,and overcoming these resistances represents a major unmet clinical *** this review,we summarize the acquired resistance mechanism of the first-and second-generation TRK inhibitors,and firstly put forward the emerging selective type Ⅱ TRK inhibitors to overcome xDFG mutations mediated ***,we concluded our perspectives on new challenges and future directions in this field.

关键词： NTRK fusions TRK kinase Clinical resistance xDFG mutations Selective type II inhibitors

Group Decision-Making Method with Incomplete Intuitionistic Fuzzy Preference Relations Based on a Generalized Multiplicative Consistent Concept

在线全文

学校读者我要写书评

暂无评论

Computer Modeling in Engineering & Sciences 2022年第9期132卷 881-907页

作者： xiaoyun lu Jiuying Dong Hecheng Li Shuping Wan School of Computer Science Qinghai Normal UniversityXining810008China School of Science Shanghai Institute of TechnologyShanghai201418China School of Statistics Jiangxi University of Finance and EconomicsNanchang330013China School of Information Technology Jiangxi University of Finance and EconomicsNanchang330013China

Based on the analyses of existing preference group decision-making(PGDM)methods with intuitionistic fuzzy preference relations(IFPRs),we present a new PGDM framework with incomplete IFPRs.A generalized multiplicative consistent for IFPRs is defined,and a mathematical programming model is constructed to supplement the missing values in incomplete ***,in this study,another mathematical programming model is constructed to improve the consistency level of unacceptably multiplicative consistent *** group decisionmaking(GDM)with incomplete IFPRs,three reliable sources influencing the weights of experts are ***,a method for determining the weights of experts is developed by simultaneously considering three reliable ***,a targeted consensus process(CPR)is developed in this study with reference to the actual situation of the consensus level of each ***,in response to the proposed multiplicative consistency definition,a novel method for determining the optimal priority weights of alternatives is ***,based on the above theory,a novel GDM method with incomplete IFPRs is developed,and the comparative and sensitivity analysis results demonstrate the utility and superiority of this work.

关键词： Intuitionistic fuzzy preference relations multiplicative consistency consensus optimization model group decision-making

Cyclization mechanism of monoterpenes catalyzed by monoterpene synthases in dipterocarpaceae

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Synthetic and Systems Biotechnology 2024年第1期9卷 11-18页

作者： xiaoyun lu Jie Bai Zunzhe Tian Congyu Li Nida Ahmed Xiaonan Liu Jian Cheng Lina lu Jing Cai Huifeng Jiang Wen Wang School of Ecology and Environment Northwestern Polytechnical UniversityXi’anShanxi710072China Key Laboratory of Engineering Biology for Low-Carbon Manufacturing Tianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjin300308China

Monoterpenoids are typically present in the secretory tissues of higher plants,and their biosynthesis is catalyzed by the action of monoterpene synthases(MTSs).However,the knowledge about these enzymes is restricted in a few plant *** are responsible for the complex cyclization of monoterpene precursors,resulting in the production of diverse monoterpene *** enzymatic reactions are considered exceptionally complex in ***,it is crucial to understand the catalytic mechanism of MTSs to elucidate their ability to produce diverse or specific monoterpenoid *** our study,we analyzed thirteen genomes of Dipterocarpaceae and identified 38 MTSs that generate a variety of monoterpene *** focusing on four MTSs with different product spectra and analyzing the formation mechanism of acyclic,monocyclic and bicyclic products in MTSs,we observed that even a single amino acid mutation can change the specificity and diversity of MTS products,which is due to the synergistic effect between the shape of the active cavity and the stabilization of carbon-positive intermediates that the mutation ***,residues N340,I448,and phosphoric acid groups were found to be significant contributors to the stabilization of intermediate terpinyl and pinene *** in these residues,either directly or indirectly,can impact the synthesis of single monoterpenes or their *** revealing the role of key residues in the catalytic process and establishing the interaction model between specific residues and complex monoterpenes in MTSs,it will be possible to reasonably design and engineer different catalytic activities into existing MTSs,laying a foundation for the artificial design and industrial application of MTSs.

关键词： Cyclization Monoterpene synthases Intermediate stabilization

Design,synthesis,and biological evaluation of Bcr-Abl PROTACs to overcome T315I mutation

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2021年第5期11卷 1315-1328页

作者： Liang Jiang Yuting Wang Qian Li Zhengchao Tu Sihua Zhu Sanfang Tu Zhang Zhang Ke Ding xiaoyun lu Intemational Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development Ministry of Education(MOE)of ChinaSchool of PharmacyJinan UniversityGuangzhou 510632China Department of Hematology Zhujiang HospitalSouthern Medical UniversityGuangzhou 510282China

Bcr-Abl threonine 315 to isoleucine 315(T315 I)gatekeeper mutation induced drug resistance remains an unmet clinical challenge for the treatment of chronic myeloid leukemia(CML).Chemical degradation of Bcr-AblT315 Iprotein has become a potential strategy to overcome drug ***,we first described the design,synthesis,and evaluation of a new class of selective Bcr-AblT315 I proteolysis-targeting chimeric(PROTAC)degraders based on GZD824(reported as Bcr-AblT315 Iinhibitor by our group).One of the degrader 7 o with 6-member carbon chain linkage with pomalidomide exhibits the most potent degradation efficacy with DR of 69.89%and 94.23%at 100 and 300 nmol/L,respectively,and has an IC50 value of 26.8±9.7 nmol/L against Ba/F3T315 ***,7 o also displays substantial tumor regression against Ba/F3-Bcr-AblT315 Ixenograft model in vivo.

关键词： CML PROTAC Degradation T315I mutation Clinical resistance

Strategies of polyhydroxyalkanoates modification for the medical application in neural regeneration/nerve tissue engineering

在线全文

学校读者我要写书评

暂无评论

Advances in Bioscience and Biotechnology 2013年第6期4卷 731-740页

作者： xiaoyun lu Leilei Wang Zhiqian Yang Haixia lu Institute of Neurobiology Xi’an Jiaotong University College of Medicine Xi’an China Key Laboratory of Biomedical Information Engineering of Ministry of Education School of Life Science and Technology Xi’an Jiaotong University Xi’an China

Neural regeneration was once considered to be impossible, especially in the central nervous system where neural regeneration comprise the generation of new neurons, glia, axons, myelin, and synapses. Until recently, neural stem cells/neural progenitor cells (NSCs/NPCs) were identified from various areas of brain and brought hopes to the neural repair and regeneration. Tissue engineering has revolutionized the current neural regeneration technology and it has become a pioneering interdisciplinary field in the areas of biomedical research. Polyhydoxyalkanoate (PHA) as one of biodegradable material has been successfully used as tissue engineering materials. It has also been applied in nerve tissue engineering due to the high biocompatibility and low cytotoxicity. Over the past 10 years, different kinds of modification strategies have been undertaken to improve the properties of PHA to fit the requirements from various fields. Several members of PHA family have been attempted for neural regeneration. This article reviewed the recent modification strategies for improving the properties of PHA and highlighted the pioneer applications in neural regeneration.

关键词： PHA Modification Neural Regeneration Nerve Tissue Engineering

2-Oxo-3,4-dihydropyrimido[4,5-d] pyrimidines as new reversible inhibitors of EGFR C797S(Cys797 to Ser797)mutant

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2020年第5期31卷 1281-1287页

作者： Xianglong Hu Qiuju Xun Tao Zhang Su-Jie Zhu Qian Li Linjiang Tong Mengzhen Lai Tao Huang Cai-Hong Yun Hua Xie Ke Ding xiaoyun lu International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) School of PharmacyJinan UniversityGuangzhou 510632China Division of Antitumor Pharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Institute for Translational Medicine College of MedicineQingdao UniversityQingdao 266021China Department of Biochemistry and Biophysics Institute of Systems BiomedicineSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China

Extensive structure-activity relationships(SARs)study of JND3229 was conducted to yield a series of new reve rsible 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidine privileged scaffold as EGFRC797 S *** of the most potent compound 6 i potently suppressed EGFRL858 R/T790 M/C797 S kinase with an IC50 value of 3.1 nmol/L,and inhibited the proliferation of BaF3 cells harboring EGFRL858 R/T790 M/C797 S and EGFR19 D/T790 M/C797 S mutants with IC50 values of 290 nmol/L and 316 nmol/L,***,6 i dose-dependently induced suppression of the phosphorylation of EGFRL858 R/T790 M/C797 S and EGFR19 D/T790 M/C797 S in BaF3 *** 6 i may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer(NSCLC)patients.

关键词： EGFRC797S mutant SARs 2-Oxo-3,4-dihydropyrimido[4,5-d] pyrimidine Clinical resistance Fourth-generation inhibitors

在线全文

学校读者我要写书评

暂无评论

犹豫模糊粒计算中信息熵研究

计算机工程与应用 2017年第7期53卷 171-176页

作者：鲁小云青海师范大学计算机学院西宁810008

基于犹豫模糊粒度结构理论,结合Shannon熵和梁吉业等人提出的新熵概念,给出Ι型和Π型犹豫模糊信息熵、联合熵、条件熵概念,讨论了两类犹豫模糊信息熵的偏序性,分析了给出的犹豫模糊信息熵、联合熵、条件熵与已存在的各类相关熵之间的... 详细信息

基于犹豫模糊粒度结构理论,结合Shannon熵和梁吉业等人提出的新熵概念,给出Ι型和Π型犹豫模糊信息熵、联合熵、条件熵概念,讨论了两类犹豫模糊信息熵的偏序性,分析了给出的犹豫模糊信息熵、联合熵、条件熵与已存在的各类相关熵之间的关系。

关键词：犹豫模糊粒度结构犹豫模糊信息熵犹豫模糊信息联合熵犹豫模糊信息条件熵

New techniques and strategies in drug discovery

在线全文

学校读者我要写书评

暂无评论

Chinese Chemical Letters 2020年第7期31卷 1695-1708页

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 Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical SciencesJi'nan 250117China School of Pharmacy Ji'nan UniversityGuangzhou 510632China Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJi'nan 250012China Department of Chemistry Jiangsu Key Laboratory of Drug Design and OptimizationChina Pharmaceutical UniversityNanjing 211198China Stare Key Laboratory of Biotherapy and Cancer Center West China Hospitaland Collaborative Innovation Center of BiotherapySichuan UniversityChengdu 610041China Stare Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesChina Pharmaceutical UniversityNanjing 210009China Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education West China School of PharmacySichuan UniversityChengdu 610041China Key Laboratory of Pesticide&Chemical Biology(CCNU) Ministry of EducationDepartment of ChemistryCentral China Normal UniversityWuhan 430079China

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

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

在线全文

学校读者我要写书评

暂无评论

试论国土资源类期刊选题策划的特点

中国科技期刊研究 2007年第3期18卷 495-497页

作者：陆小芸 <南方国土资源>杂志社广西南宁市建政路1号530023

选题策划是编辑出版工作的龙头,做好选题策划有利于掌握出版工作的主动权,提高期刊质量。本文时国土资源类期刊的选题策划的特点,即宏观与微观,静态与动态,共性与个性进行归纳总结、分析探讨,旨在提高国土资源类期刊的办刊质量,避免工... 详细信息

选题策划是编辑出版工作的龙头,做好选题策划有利于掌握出版工作的主动权,提高期刊质量。本文时国土资源类期刊的选题策划的特点,即宏观与微观,静态与动态,共性与个性进行归纳总结、分析探讨,旨在提高国土资源类期刊的办刊质量,避免工作的随意性、盲目性。

关键词：国土资源期刊宏观选题策划微观选题策划