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Degradation of proteins by PROTACs and other strategies

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Acta Pharmaceutica Sinica B 2020年第2期10卷 207-238页

作者： Yang Wang Xueyang Jiang Feng Feng Wenyuan Liu haopeng sun Department of Pharmaceutical Analysis Key Laboratory of Drug Quality Control and PharmacovigilanceMinistry of EducationChina Pharmaceutical UniversityNanjing 210009China Department of Natural Medicinal Chemistry China Pharmaceutical UniversityNanjing 211198China Jiangsu Food and Pharmaceutical Science College Huaian 223003 China Department of Medicinal Chemistry China Pharmaceutical UniversityNanjing 211198China

Abnormal protein expression or activities are associated with many diseases,especially ***,down-regulating the proteins involved in cancer cell survival proved to be an effective strategy for cancer treatment—a number of drugs based on proteolysis-targeting chimaera(PROTAC)mechanism have demonstrated clinical *** progress in the PROTAC strategy includes identification of the structure of the first ternary eutectic complex,extra-terminal domain-4-PROTAC-VonHippel-Lindau(BRD4-PROTAC-VHL),and PROTAC ARV-110 has entered clinical trials for the treatment of prostate cancer in *** discoveries strongly proved the value of the PROTAC *** this review,we summarize recent meaningful research of PROTACs,including the molecular design and optimization strategy as well as clinical application of candidate *** hope to provide useful insights for rational design of PROTACs.

关键词： Protein degradation PROTAC Ubiquitin-proteasome system E3 ubiquitin ligase Target protein Heterobifunctional molecule

New insight into targeting the DNA damage response in the treatment of glioblastoma

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Chinese Journal of Natural Medicines 2024年第10期22卷 869-886页

作者： ZHEN Tengfei sun Tianyu XIONG Baichen LIU Hui WANG Lei CHEN Yao sun haopeng School of Pharmacy China Pharmaceutical UniversityNanjing 211198China Department of Chemistry Tsinghua UniversityBeijing 100084China School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China

Glioblastoma(GBM)is the most common invasive malignant tumor in human brain tumors,representing the most severe grade of *** existing therapeutic approaches,patient prognosis remains dismal,necessitating the exploration of novel strategies to enhance treatment efficacy and extend *** to the restrictive nature of the blood-brain barrier(BBB),smallmolecule inhibitors are prioritized in the treatment of central nervous system *** these,DNA damage response(DDR)inhibitors have garnered significant attention due to their potent therapeutic potential across various *** review provides a detailed analysis of DDR pathways as therapeutic targets in GBM,summarizes recent advancements,therapeutic strategies,and ongoing clinical trials,and offers perspectives on future directions in this rapidly evolving *** goal is to present a comprehensive outlook on the potential of DDR inhibitors in improving GBM management and outcomes.

关键词： Glioblastoma DNA damage response Small molecule inhibitors

Docking Study and Three-Dimensional Quantitative Structure- Activity Relationship （3D-QSAR） Analyses and Novel Molecular Design of a Series of 4-Aminoquinazolines as Inhibitors of Aurora B Kinase

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Chinese Journal of Chemistry 2011年第9期29卷 1785-1799页

作者： sun, haopeng Zhu, Jia Chen, Yadong sun, Yuan Zhi, Huijing Li, Hao You, Qidong Key Laboratory of Carcinogenesis and Intervention of Jiangsu Province China Pharmaceutical University Nanjing Jiangsu 210009 China Department of Medicinal Chemistry China Pharmaeeutical University Nanjing Jiangsu 210009 China

The Aurora proteins are critical regulators of major mitotic events and attractive targets for anticancer therapy. 3D-QSAR studies based on molecular docking were performed on a dataset of 40 4-aminoquinazolines compounds. The CoMSIA model produced significantly better results than CoMFA model, with q2=0.652 and r2=0.991. The contours analysis provides useful information about the structural requirements for 4-aminoquinazolines for inhib- iting Aurora B. Scaffold hopping method was used to generate new structures based on the maximum common sub- structure of the training and test set compounds. The ADMET property, binding affinity and inhibitory activity of the new designed compounds were predicted, respectively. Finally 16 compounds were identified as the novel in- hibitors for Aurora B kinase.

关键词： 4-aminoquinazolines 3D-QSAR molecular modeling quantum chemistry CoMSIA aurora B inhibitors

Discovery of Tryptophan-tetrahydroisoquinoline Derivatives as Multifunctional Agents for Treatment of Alzheimer's Disease

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Chinese Journal of Chemistry 2022年第15期40卷 1821-1830页

作者： Xin Lu Yijun Liu Nan Qin Chenxi Du Yanyu Hu Yao Chen haopeng sun School of Pharmacy China Pharmaceutical UniversityNanjingJiangsu 211198China School of Pharmacy Nanjing University of Chinese MedicineNanjingJiangsu 210023China Department of Natural Medicinal Chemistry China Pharmaceutical UniversityNanjingJiangsu 211198China

Comprehensive Summary The cholinesterases are essential targets implicated in the pathogenesis of Alzheimer's disease(AD).We have identified tryptophan-tetrahydroisoquinoline derivatives as selective micro-nanomolar butyrylcholinesterase(BChE)*** docking was applied for the rational design and binding mode *** were defined according to their target inhibitory activity,low cytotoxicity,predicted permeability through the blood-brain barrier(BBB),and in vivo cognitive ***,the preferred compound showed ability to decrease self-induced Aβ1-42 aggregation and Aβ1-42 induced SH-SY5Y cell ***,these factors indicated their potential as unique lead compounds for AD treatment.

关键词： Alzheimer's disease Butyrylcholinesterase Inhibitors Molecular modeling Biological activity

A Practical and High-Affinity Fluorescent Probe for Butyrylcholinesterase:A Good Strategy for Binding Affinity Characterization

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Chinese Journal of Chemistry 2022年第11期40卷 1285-1292,I0002页

作者： Lei Wang Chenxi Du Hui Liu Weimin Qiu Xin Lu Yanyu Hu Yueqing Li Tianyu sun Yao Chen haopeng sun School of Pharmacy China Pharmaceutical UniversityNanjingJiangsu 211198China Department of Natural Medicinal Chemistry China Pharmaceutical UniversityNanjingJiangsu 211198China School of Pharmacy Nanjing University of Chinese MedicineNanjingJiangsu 210023China

Butyrylcholinesterase(BChE)is regarded as a promising target for the treatment of Alzheimer's disease(AD),as its level significantly increases along with the progress of this ***,the development of potent and high-affinity small-molecule BChE inhibi-tors may be a new strategy for the discovery of anti-AD ***,the current Ellman's method is unable to evaluate the affinity of compounds with BChE,and has a few deficiencies in drug ***,the first small-molecule fluorescence polarization(FP)probes for BChE were rationally designed based on a high affinity *** indicated that probe F6 exhibited satisfactory fluorescence intensity and suitable fluorescent properties that were compatible with the filters in the FP ***,probe F6 exhibited potent binding affinity to *** is feasible to be applied in detecting the affinity of non-fluorescent compounds to BChE,which lays a solid foundation for the development of small-molecule BChE *** the same time,it also can be applied as a val-uable chemical tool for better understanding the molecular biological mechanism of BChE.

关键词： Butyrylcholinesterase Alzheimer's disease Fluorescent probes Inhibitors High-throughput screening

QoS-Aware Power Allocation Scheme for Relay Satellite Networks

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Journal of Beijing Institute of Technology 2021年第1期30卷 82-90页

作者： Jin’ao Yu Xiaogang Tang Shibing Zhu haopeng sun Lunxin Zhong Guangyu Yang School Space Engineering UniversityBeijing 101416China School of Space Information Space Engineering UniversityBeijing 101416China

This paper investigated a QoS-aware power allocation for relay satellite *** the given QoS requirements,we analyzed the signal model of relay transmission and formulated the power minimization problem which is non-convex and difficult to *** find the optimal solution to the considered problem,we first analyzed the optimization problem and equivalently turn it into a convex optimization ***,we provided a Lagrangian dual-based method to obtain the closed-form of the power allocation and provided an iterative algorithm to the optimal ***,we also extended the results to the cooperative transmission ***,simulation results were provided to verify the superiority of the proposed algorithm.

关键词： power allocation relay satellite network quality of service cooperative transmission

2-Diphenylphosphinoyl-acetyl as a Remote Directing Group for the Highly Stereoselective Synthesis ofβ-Glycosides

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Chinese Journal of Chemistry 2022年第4期40卷 443-452页

作者： Xianglai Liu Yetong Lin Ao Liu Qianhui sun Huiyong sun Peng Xu Guolong Li Yingying Song Weijia Xie haopeng sun Biao Yu Wei Li Department of Medicinal Chemistry School of PharmacyChina Pharmaceutical University639 Longmian AvenueNanjingJiangsu 211198China State Key Laboratory of Bioorganic and Natural Products Chemistry Shanghai Institute of Organic ChemistryChinese Academy of Sciences345 Lingling RoadShanghai 200032China

Comprehensive Summary The configuration of the anomeric glycosidic linkages is crucial for maintaining the biological functions and activities of carbohydrate ***,their stereochemistry control in glycosylation represe... 详细信息

关键词： Glycosylation Diastereoselectivity Hydrogen bonds 2-Diphenylphosphinoyl-acetyl 2-Deoxy sugars

Therapeutic strategies of glioblastoma (GBM):The current advances in the molecular targets and bioactive small molecule compounds

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1781-1804页

作者： Hui Liu Weimin Qiu Tianyu sun Lei Wang Chenxi Du Yanyu Hu Wenyuan Liu Feng Feng Yao Chen haopeng sun School of Pharmacy China Pharmaceutical UniversityNanjing 211198China School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China Jiangsu Drug Development Engineering Research Center for Central Degenerative Disease Jiangsu Food and Pharmaceuticals Science CollegeHuaian 223005China Department of Natural Medicinal Chemistry China Pharmaceutical UniversityNanjing 211198China Department of Pharmaceutical Analysis Key Laboratory of Drug Quality Control and PharmacovigilanceChina Pharmaceutical UniversityNanjing 211198China

Glioblastoma(GBM)is the most common aggressive malignant tumor in brain neuroepithelial tumors and remains incurable.A variety of treatment options are currently being explored to improve patient survival,including small molecule inhibitors,viral therapies,cancer vaccines,and monoclonal *** them,the unique advantages of small molecule inhibitors have made them a focus of attention in the drug discovery of ***,the most used chemotherapeutic agents are small molecule inhibitors that target key dysregulated signaling pathways in glioblastoma,including receptor tyrosine kinase,PI3K/AKT/mTOR pathway,DNA damage response,TP53 and cell cycle *** review analyzes the therapeutic benefit and clinical development of novel small molecule inhibitors discovered as promising anti-glioblastoma agents by the related targets of these major ***,the recent advances in temozolomide resistance and drug combination are also *** the last part,due to the constant clinical failure of targeted therapies,this paper reviewed the research progress of other therapeutic methods for glioblastoma,to provide patients and readers with a more comprehensive understanding of the treatment landscape of glioblastoma.

关键词： Glioblastoma Small molecule inhibitors Targeted therapy Clinical trials Temozolomide Combination therapy

破解数字异化：迈向数字社会主义——对克里斯蒂安·福克斯思想的批判性考察

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世界社会科学 2024年第3期 136-149+245页

作者：孙昊鹏复旦大学马克思主义学院

数字资本主义引发的数字异化现象已成为现代人面临的生存困境。福克斯借助“数字异化矩阵”,从经济、政治和文化三个维度，对数字资本主义展开批判，并结合马克思主义经典论述，提出数字社会主义将更为平等、民主和包容。在他看来，实... 详细信息

数字资本主义引发的数字异化现象已成为现代人面临的生存困境。福克斯借助“数字异化矩阵”,从经济、政治和文化三个维度，对数字资本主义展开批判，并结合马克思主义经典论述，提出数字社会主义将更为平等、民主和包容。在他看来，实现数字社会主义需发展批判性理论和批判性教育，依靠数字工人联合起来进行社会运动。这些观点虽有一定的抽象思辨色彩和革命浪漫主义倾向，但也继承了西方马克思主义现代性批判理论辩证性和现实性的特点。中国学者应致力于扩大数字中国的影响力，参与到国外关于数字社会主义的讨论中去。

关键词：福克斯数字异化数字社会主义数字中国