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Discovery of a highly potent and selective Bruton’s tyrosine kinase inhibitor avoiding impairment of ADCC effects for B-cell non-Hodgkin lymphoma

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Signal Transduction and Targeted Therapy 2020年第1期5卷 814-816页

作者： Juan liu Qianmao Liang Aoli Wang Fengming Zou Ziping Qi Kailin Yu qingwang liu Cheng Chen Jing liu Qingsong liu Anhui Province Key Laboratory of Medical Physics and Technology Institute of Health and Medical TechnologyHefei Institutes of Physical ScienceChinese Academy of Sciences230031 HefeiAnhuiP.R.China University of Science and Technology of China 230036 HefeiAnhuiP.R.China Hefei Cancer Hospital Chinese Academy of Sciences230031 HefeiAnhuiP.R.China Precision Medicine Research Laboratory of Anhui Province 230088 HefeiAnhuiP.R.China Precision Targeted Therapy Discovery Center Institute of Technology InnovationHefei Institutes of Physical ScienceChinese Academy of Sciences230088 HefeiAnhuiP.R.China Institutes of Physical Science and Information Technology Anhui University230601 HefeiAnhuiP.R.China

Dear Editor,Bruton’s tyrosine kinase(BTK)plays a crucial role in the B-cell receptor(BCR)signaling which is essential for B-cell proliferation,differentiation,and cell *** BCR activation has been identified as a major pathogenic factor in several B-cell non-Hodgkin lymphoma(B-NHL)subtypes,including diffuse large Bcell lymphoma(DLBCL),mantle cell lymphoma(MCL),follicular lymphoma(FL),and chronic lymphocytic leukemia(CLL).1 Therefore,BTK has been recognized as a validated therapeutic target for B-cell ***,the first approved BTK inhibitor that binds irreversibly to cysteine residue 481,has shown potent clinical activity in the majority of CD20 positive B-cell malignancies.2 However,due to the inhibition of off-target kinases such as EGFR,ITK,and TXK,which have a cysteine residue at the identical position of Cys481 of BTK,Ibrutinib also results in some adverse events,such as the antagonizing Rituximab-dependent NK-cell-mediated antibody-dependent cell-mediated cytotoxicity(ADCC)due to its irreversible binding to ITK,which is required for FcR-stimulated NK cell function.3 Although several secondary generation inhibitors have shown improved selectivity,4,5 more pharmacologically diverse novel inhibitors are still highly demanded in the clinic.

关键词： lymphoma ADCC lymphocytic

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Discovery of a highly selective VEGFR2 kinase inhibitor CHMFL-VEGFR2-002 as a novel antiangiogenesis agent

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Acta Pharmaceutica Sinica B 2020年第3期10卷 488-497页

作者： Zongru Jiang Li Wang Xuesong liu Cheng Chen Beilei Wang Wenliang Wang Chen Hu Kailin Yu Ziping Qi qingwang liu Aoli Wang Jing liu Guangchen Hong Wenchao Wang Qingsong liu High Magnetic Field Laboratory Key Laboratory of High Magnetic Field and Ion Beam Physical BiologyHefei Institutes of Physical ScienceChinese Academy of SciencesHefei 230031China University of Science and Technology of China Hefei 230026China Precision Targeted Therapy Discovery Center Institute of Technology InnovationHefei Institutes of Physical ScienceChinese Academy of SciencesHefei 230088China Precision Medicine Research Laboratory of Anhui Province Hefei 230088China Qingdao Shinan District People's Hospital Qingdao 266002China Institutes of Physical Science and Information Technology Anhui UniversityHefei 230601China

Angiogenesis is an essential process in tumor growth,invasion and *** receptor 2(VEGFR2)inhibitors targeting tumor angiogenic pathway have been widely used in the clinical cancer ***,most of currently used VEGFR2 kinase inhibitors are multi-target inhibitors which might result in target-associated side effects and therefore limited clinical *** selective VEGFR inhibitors are still highly demanded from both basic research and clinical application point of *** we report the discovery and characterization of a novel VEGFR2 inhibitor(CHMFLVEGFR2-002),which exhibited high selectivity among structurally closed kinases including PDGFRs,FGFRs,CSF1 R,***-VEGFR2-002 displayed potent inhibitory activity against VEGFR2 kinase in the biochemical assay(IC50=66 nmol/L)and VEGFR2 autophosphorylation in cells(EC50s^100 nmol/L)as well as potent anti-proliferation effect against VEGFR2 transformed BaF3 cells(GI50=150 nmol/L).In addition,CHMFL-VEGFR2-002 also displayed good anti-angiogenesis efficacy in vitro and exhibited good in vivo PK(pharmacokinetics)profile with bioavailability over 49%and antiangiogenesis efficacy in both zebrafish and mouse models without apparent *** results suggest that CHMFL-VEGFR2-002 might be a useful research tool for dissecting new functions of VEGFR2 kinase as well as a potential anti-angiogenetic agent for the cancer therapy.

关键词： Cancer VEGFR2 kinase Kinase inhibitor Angiogenesis Inhibitor selectivity

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Discovery of IHMT-MST1-39 as a novel MST1 kinase inhibitor and AMPK activator for the treatment of diabetes mellitus

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2278-2290页

作者： Junjie Wang Ziping Qi Yun Wu Aoli Wang qingwang liu Fengming Zou Beilei Wang Shuang Qi Jiangyan Cao Chen Hu Chenliang Shi Qianmao Liang Li Wang Jing liu Wenchao Wang Qingsong liu Anhui Province Key Laboratory of Medical Physics and Technology Institute of Health and Medical TechnologyHefei Institutes of Physical ScienceChinese Academy of SciencesHefeiAnhui230031P.R.China University of Science and Technology of China HefeiAnhui230026P.R.China Hefei Cancer Hospital Chinese Academy of SciencesHefeiAnhui230031P.R.China Precision Medicine Research Laboratory of Anhui Province HefeiAnhui230088P.R.China

Insulin-producing pancreaticβcell death is the fundamental cause of type 1 diabetes(T1D)and a contributing factor to type 2 diabetes(T2D).Moreover,metabolic disorder is another hallmark of *** sterile 20-like kinase 1(MST1)contributes to the progression of diabetes mellitus through apoptosis induction and acceleration of pancreaticβcell ***-activated protein kinase(AMPK)is an energy sensing kinase and its activation has been suggested as a treatment option for metabolic ***,pharmacological inhibition of MST1 and activation of AMPK simultaneously represents a promising approach for diabetes ***,we discovered a novel selective MST1 kinase inhibitor IHMT-MST1-39,which exhibits anti-apoptosis efficacy and improves the survival of pancreaticβcells under diabetogenic conditions,as well as primary pancreatic islets in an ex vivo disease ***,IHMT-MST1-39 activated AMPK signaling pathway in hepatocytes in vitro,combination of IHMT-MST1-39 and metformin synergistically prevented hyperglycemia and significantly ameliorated glucose tolerance and insulin resistance in diabetic *** together,IHMT-MST1-39 is a promising anti-diabetic candidate as a single agent or in combination therapy for both T1D and T2D.

关键词： diabetes mellitus treatment

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The Synthesize and Property Evaluation of High Temperature Resistant Phenolic Resin-Type Profile Control Agent

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Open Journal of Composite Materials 2014年第3期4卷 173-176页

作者： qingwang liu Hongwei Mu Jigang Wang Zhenzhong Fan EOR Key Laboratory of the Ministry of Education Northeast Petroleum University Daqing City China

Most of the mining method of domestic oilfield is waterflood development, thus the water content in the mid and late water flooding would rise faster, and the oil recovery rate would decline relatively more rapid. So it is very important to research profile control agent for stabilizing oil production resin-type profile control agent, and focus on researching the themal stability, shear resistance, gelation time and gelation strength and other properties of this profile control agent?[1]. Finally, the best ratio for synthesizing the high temperature resistant phenolic resin-type profile control agent was obtained.

关键词： Waterflood Development Phenolic Resin Profile Control Agent

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Performance Evaluation of a New Type of Polymer Profile Control Agent

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Materials Sciences and Applications 2015年第5期6卷 348-352页

作者： qingwang liu Zhe Zhang Zhenzhong Fan Zhenzhong Fan Jigang Wang EOR Key Laboratory of the Ministry of Education Northeast Petroleum University Daqing City China

The low-permeability oil and gas resources of our country are quite common and abundant. Their reserve has accounted for one-fifth of total oil reserves of our country, and their yield has constituted the important part of national petroleum annual yield, but its development is very difficult. Polymer gel technology is a technical method of improving sweep efficiency in recent years which substantially increases the viscosity of the polymer solution by adding a crosslinking agent to the polymer produced by intramolecular or intermolecular crosslinking.

关键词： Low-Permeability Polymer Gel Profile Control Agent

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The Synthesis and Evaluation of Hydrophobic Association Thickener

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Open Journal of Composite Materials 2015年第1期5卷 1-4页

作者： qingwang liu Dong Cheng Jigang Wang Zhenzhong Fan Tong Zhang Ao Sun EOR Key Laboratory of the Ministry of Education Northeast Petroleum University Daqing City China

The paper provides a new hydrophobic association polymer fracturing fluid gelatinizer. The hydrophobic association which is the synthesis of three component copolymer complexes, is compounded by micellar copolymerization method. The hydrophobic association is got together through hydrophilic monomer acrylamide monomer N,N-vinyl pyrrolidone monomer with a rigid group N, and hydrophobic monomer N,N-2 dodecyl acrylamide etc. three monomers with sodium dodecyl sulfate as the emulsifier in micellar solution.

关键词： Hydrophobic Association Fracturing Fluid Surface Active Agent Three Component Copolymer Apparent Viscosity

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Synthesis and Performance Evaluation of Organic Bentonite Modifier Dimethyldistearylammonium Bromide (DODMAB)

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Open Journal of Composite Materials 2014年第4期4卷 220-223页

作者： qingwang liu Ao Sun Zhenzhong Fan Jiguang Wang Tong Zhang Dong Cheng Northeast Petroleum University Daqing China

Dimethyldistearylammonium Bromide (DODMAB) is a bentonite modifier with good performance. In this experiment, 1-Bromooctadecane is the raw material, and completes tertiary amination and quaternization successively by changing the condition of experiment. The result is that the productivity can achieve 78.94% in the synthesis of DODMAB. It has been used in the experiment of bentonite modification and achieves good results;compared with using trimethylstearylammonium bromide as the organic modifier, the synthetic organic bentonite has better performance than the common organic modifier when used in the oil base drilling fluid of oilfield operation.

关键词： Organic Modifier Stepwise Synthesis Performance Evaluation

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激光雷达森林参数反演研究进展

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遥感学报 2016年第5期20卷 1138-1150页

作者：李增元刘清旺庞勇中国林业科学研究院资源信息研究所林业遥感与信息技术重点开放性实验室北京100091

激光雷达通过发射激光能量和接收返回信号的方式,来获取高精度的森林空间结构和林下地形信息。全波形激光雷达通过记录返回信号的全部能量,得到亚米级植被垂直剖面;离散回波激光雷达记录的单个或多个回波,表示来自不同冠层的回波信号。... 详细信息

激光雷达通过发射激光能量和接收返回信号的方式,来获取高精度的森林空间结构和林下地形信息。全波形激光雷达通过记录返回信号的全部能量,得到亚米级植被垂直剖面;离散回波激光雷达记录的单个或多个回波,表示来自不同冠层的回波信号。星载激光雷达一般采用全波形或光子计数激光剖面系统,仅能获取卫星轨道下方的单波束或多波束数据,用于区域/全球范围的森林垂直结构及变化观测。机载激光雷达多采用离散回波或全波形激光扫描系统,能够获取飞行轨迹下方特定视场范围内的扫描数据,用于林分/区域范围的森林结构观测。地基激光雷达多采用离散回波激光扫描系统,获取以测站为中心的球形空间内扫描数据,用于单木/样地范围的森林结构观测。激光雷达单木因子估测方法可分为CHM单木法、NPC单木法和体元单木法3类。CHM单木法通过局部最大值识别树冠顶点,采用区域生长或图像分割算法识别树冠边界或树冠主方向,NPC单木法一般通过空间聚类或形态学算法识别单木,体元单木法在3维体元空间采用区域生长或空间聚类算法识别树冠。根据激光雷达冠层高度分布可以估测林分因子,冠层高度分布特征来自于离散点云或全波形。多时相激光雷达可用于森林生长量、生物量变化等监测,以及森林采伐、灾害等引起的结构变化监测。随着激光雷达技术的发展,它将在森林调查、生态环境建模等生产与科学研究领域中得到更为广泛的应用。

关键词：激光雷达森林单木林分

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The Synthesis and Evaluation of a Novel Inhibitor DN for Carbon Dioxide Corrosion

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Open Journal of Composite Materials 2014年第4期4卷 215-219页

作者： qingwang liu Tong Zhang Jigang Wang Zhenzhong Fan Ao Sun Dong Cheng EOR Key Laboratory of the Ministry of Education Northeast Petroleum University Daqing China

During the oil and gas wells exploitation and transportation, carbon dioxide corrosion is one of main reasons for the corrosion of metallic materials. So the methods of preventing and reducing carbon dioxide corrosion have become a widely focused problem. The foreign and domestic practices and experiences show that as an economic, effective and versatile metal corrosion control method, corrosion inhibitor protection technology is suitable for application in oil and gas transportation system. This paper, through the indoor experiment with benzyl chloride, using quinoline as raw materials, synthesizes a kind of quinoline quaternary ammonium salt. The obtained product benzyl chloride quinoline compounded with OP-10 and ethanol to get a novel inhibitor DN for carbon dioxide corrosion, and to evaluate its performance.

关键词： Carbon Dioxide Corrosion Inhibitor Synthesis Method Performance Evolution

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IMPROVING　OIL　WELL　CEMENTING　QUALITY　WITH　MAGNETIZED　CEMENT　SLURRY　IN　DAQING　OIL　FIELD

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Scientia Geologica Sinica 1996年第2期 237-244页

作者： Luo Yun Sun Weilin Wang Tie inn and liu qingwang(Daqing Petroleum institute, Anda 151400)

ＩＭＰＲＯＶＩＮＧＯＩＬＷＥＬＬＣＥＭＥＮＴＩＮＧＱＵＡＬＩＴＹＷＩＴＨＭＡＧＮＥＴＩＺＥＤＣＥＭＥＮＴＳＬＵＲＲＹＩＮＤＡＱＩＮＧＯＩＬＦＩＥＬＤ￥ＬｕｏＹｕｎ；ＳｕｎＷｅｉｌｉｎ；ＷａｎｇＴｉｅｉｎｎａｎｄＬｉｕ...

ＩＭＰＲＯＶＩＮＧＯＩＬＷＥＬＬＣＥＭＥＮＴＩＮＧＱＵＡＬＩＴＹＷＩＴＨＭＡＧＮＥＴＩＺＥＤＣＥＭＥＮＴＳＬＵＲＲＹＩＮＤＡＱＩＮＧＯＩＬＦＩＥＬＤ￥ＬｕｏＹｕｎ；ＳｕｎＷｅｉｌｉｎ；ＷａｎｇＴｉｅｉｎｎａｎｄＬｉｕＱｉｎｇｗａｎｇ（ＤａｑｉｎｇＰｅ...

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