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  1. Book: Xia

    Wang, Shaozeng

    zi, ji, cong bu

    (Qing shi gao yi wen zhi shi yi : 清史稿藝文志拾遺 ; / Wang shao zeng zhu bian ; 2)

    2000  

    Series title Qing shi gao yi wen zhi shi yi : 清史稿藝文志拾遺
    / Wang shao zeng zhu bian ; 2
    Keywords China
    Language Chinese
    Size S. 1035-2560, 21 cm
    Edition Di 1 ban
    Publisher Zhong hua shu ju
    Publishing place Bei jing
    Document type Book
    ISBN 7101013643 ; 9787101013641
    Database Former special subject collection: coastal and deep sea fishing

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  2. Article ; Online: The Safety, Pharmacokinetics, and Pharmacodynamics of SHR2285, an Oral Small Molecule Factor XIa Inhibitor, in Healthy Chinese Volunteers.

    Xu, Junyu / Zhao, Nan / Huang, Jie / Li, Jinlei / Zhao, Xia / Xiang, Qian / Yang, Sibo / Dong, Yanli / Wang, Honghui / Li, Yijing / Yang, Guoping / Cui, Yimin

    Clinical drug investigation

    2023  Volume 43, Issue 6, Page(s) 435–445

    Abstract: Background and objective: There is an unmet need for a safer anticoagulant since bleeding remains a concern with currently approved anticoagulants. Coagulation factor XI (FXI) is an attractive anticoagulant drug target with limited a role in ... ...

    Abstract Background and objective: There is an unmet need for a safer anticoagulant since bleeding remains a concern with currently approved anticoagulants. Coagulation factor XI (FXI) is an attractive anticoagulant drug target with limited a role in physiological hemostasis. The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of SHR2285, a novel small molecule FXIa inhibitor, in healthy Chinese volunteers.
    Methods: The study consisted of single ascending doses part (part 1: 25-600 mg) and multiple ascending doses part (part 2: 100, 200, 300, and 400 mg). In both parts, subjects were randomized in a 3:1 ratio to receive SHR2285 or placebo orally. Blood, urine and feces samples were collected to describe its pharmacokinetic and pharmacodynamic profile.
    Results: In total, 103 healthy volunteers completed the study. SHR2285 was well tolerated. SHR2285 was absorbed rapidly with median time to maximum plasma concentration (T
    Conclusions: SHR2285 was generally safe and well tolerated in healthy subjects across a wide range of doses. SHR2285 exhibited a predictable pharmacokinetic profile and an exposure-related pharmacodynamic profile.
    Clinicaltrials: gov Identifier NCT04472819; registered on July 15, 2020.
    MeSH term(s) Humans ; Administration, Oral ; Anticoagulants/administration & dosage ; Anticoagulants/pharmacokinetics ; Anticoagulants/pharmacology ; Area Under Curve ; Dose-Response Relationship, Drug ; Double-Blind Method ; East Asian People ; Factor XIa/antagonists & inhibitors ; Healthy Volunteers
    Chemical Substances Anticoagulants ; Factor XIa (EC 3.4.21.27)
    Language English
    Publishing date 2023-06-16
    Publishing country New Zealand
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 1220136-4
    ISSN 1179-1918 ; 0114-2402 ; 1173-2563
    ISSN (online) 1179-1918
    ISSN 0114-2402 ; 1173-2563
    DOI 10.1007/s40261-023-01281-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Factor XIa Inhibitors in Anticoagulation Therapy: Recent Advances and Perspectives.

    Xie, Zhouling / Meng, Zhiwei / Yang, Xiaoxiao / Duan, Yajun / Wang, Qin / Liao, Chenzhong

    Journal of medicinal chemistry

    2023  Volume 66, Issue 8, Page(s) 5332–5363

    Abstract: Factor XIa (FXIa) in the intrinsic pathway of the coagulation process has been proven to be ...

    Abstract Factor XIa (FXIa) in the intrinsic pathway of the coagulation process has been proven to be an effective and safe target for anticoagulant discovery with limited or no bleeding. Numerous small-molecule FXIa inhibitors (SMFIs) with various scaffolds have been identified in the early stages of drug discovery. They have served as the foundation for the recent discovery of additional promising SMFIs with improved potency, selectivity, and pharmacokinetic profiles, some of which have entered clinical trials for the treatment of thrombosis. After reviewing the coagulation process and structure of FXIa, this perspective discusses the rational or structure-based design, discovery, structure-activity relationships, and development of SMFIs disclosed in recent years. Strategies for identifying more selective and druggable SMFIs are provided, paving the way for the design and discovery of more useful SMFIs for anticoagulation therapy.
    MeSH term(s) Humans ; Factor XIa ; Blood Coagulation ; Anticoagulants/pharmacology ; Thrombosis/drug therapy ; Drug Discovery
    Chemical Substances Factor XIa (EC 3.4.21.27) ; Anticoagulants
    Language English
    Publishing date 2023-04-10
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.2c02130
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Qing Xia Jie Yi Formula granules alleviated acute pancreatitis through inhibition of M1 macrophage polarization by suppressing glycolysis.

    Han, Xiao / Bao, Jingpiao / Ni, Jianbo / Li, Bin / Song, Pengli / Wan, Rong / Wang, Xingpeng / Hu, Guoyong / Chen, Congying

    Journal of ethnopharmacology

    2024  Volume 325, Page(s) 117750

    Abstract: ... of the study: This study aimed to evaluate the effect of Qing Xia Jie Yi Formula (QXJYF) granules on AP and ...

    Abstract Ethnopharmacological relevance: Herbal formulas from Traditional Chinese Medicine are common and well-established practice for treating acute pancreatitis (AP) patients. However, little is known about their bioactive ingredients and mechanisms, such as their targets and pathways to inhibit inflammation.
    Aim of the study: This study aimed to evaluate the effect of Qing Xia Jie Yi Formula (QXJYF) granules on AP and discuss the molecular mechanisms involved.
    Materials and methods: Major compounds in QXJYF granules were identified using UPLC-quadrupole-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). The effect of QXJYF granules on experimental AP models both in vitro and in vivo, and detailed mechanisms were clarified. Two AP models were induced in mice by intraperitoneally injections of caerulein or L-arginine, and QXJYF granules were used to treat AP mice in vivo. Histological evaluation of pancreas and lung, serum amylase and lipase levels, serum inflammatory cytokines, inflammatory cell infiltration and macrophage phenotype were assessed. Bone marrow derived macrophages (BMDMs) were cultured and treated with QXJYF granules in vitro. BMDM phenotype and glycolysis levels were measured. Lastly, clinical effect of QXJYF granules on AP patients was verified. Predicted severe AP (pSAP) patients eligible for inclusion were assessed for enrollment.
    Results: Nine major compounds were identified in QXJYF granules. Data showed that QXJYF granules significantly alleviated AP severity both in caerulein and L-arginine-induced AP models in vivo, pancreatic injury and inflammatory cell infiltration, systematic inflammation, lung injury and inflammatory cell infiltration were all improved after QXJYF treatment. QXJYF granules significantly reduced M1 macrophages during AP both in vivo and in vitro; besides, the mRNA expression levels of M1 genes such as inos, Tnfα, Il1β and Il6 were significantly lower after QXJYF treatment in M1 macrophages. Mechanistically, we found that HK2, PFKFB3, PKM, LDHα levels were increased in M1 macrophages, but significantly decreased after QXJYF treatment. Clinical data indicated that QXJYF granules could significantly reduce CRP levels and shorten the duration of organ failure, thereby reducing the incidence of SAP and preventing pSAP patients from progressing to SAP.
    Conclusion: QXJYF granules alleviated AP through the inhibition of M1 macrophage polarization by suppressing glycolysis.
    MeSH term(s) Humans ; Mice ; Animals ; Pancreatitis/metabolism ; Ceruletide/adverse effects ; Acute Disease ; Inflammation/drug therapy ; Macrophages ; Arginine
    Chemical Substances Ceruletide (888Y08971B) ; Arginine (94ZLA3W45F)
    Language English
    Publishing date 2024-01-10
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 134511-4
    ISSN 1872-7573 ; 0378-8741
    ISSN (online) 1872-7573
    ISSN 0378-8741
    DOI 10.1016/j.jep.2024.117750
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  5. Article ; Online: Antithrombotic Effects of the Novel Small-Molecule Factor XIa Inhibitor Milvexian in a Rabbit Arteriovenous Shunt Model of Venous Thrombosis.

    Wang, Xinkang / Li, Qiu / Du, Fuyong / Shukla, Neetu / Nawrocki, Andrea R / Chintala, Madhu

    TH open : companion journal to thrombosis and haemostasis

    2023  Volume 7, Issue 2, Page(s) e97–e104

    Abstract: ... ...

    Abstract Background
    Language English
    Publishing date 2023-04-24
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2901738-5
    ISSN 2512-9465 ; 2567-3459
    ISSN (online) 2512-9465
    ISSN 2567-3459
    DOI 10.1055/a-2061-3311
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  6. Article ; Online: Design, expression and biological evaluation of DX-88mut as a novel selective factor XIa inhibitor for antithrombosis.

    Sun, Feilong / Wang, Weihao / Li, Zhengyang / Li, Yitong / Guo, Wei / Kong, Yi

    Bioorganic chemistry

    2023  Volume 142, Page(s) 106951

    Abstract: Thrombotic diseases, such as myocardial infarction, stroke, and deep vein thrombosis, severely threaten human health, and anticoagulation is an effective way to prevent such illnesses. However, most anticoagulant drugs in the clinic have different ... ...

    Abstract Thrombotic diseases, such as myocardial infarction, stroke, and deep vein thrombosis, severely threaten human health, and anticoagulation is an effective way to prevent such illnesses. However, most anticoagulant drugs in the clinic have different bleeding risks. Previous studies have shown that coagulation factor XI is an ideal target for safe anticoagulant drug development. Here, we designed the FXIa inhibitory peptide DX-88mut by replacing Loop1 (DGPCRAAHPR) and Loop2 (IYGGC) in DX-88, which is a clinical drug targeting PKa for the treatment of hereditary angioedema, using Loop1 (TGPCRAMISR) and Loop2 (FYGGC) in the FXIa inhibitory peptide PN2KPI, respectively. DX-88mut selectively inhibited FXIa against a panel of serine proteases with an IC
    MeSH term(s) Humans ; Rats ; Mice ; Animals ; Factor XIa/metabolism ; Factor XIa/pharmacology ; Blood Coagulation ; Anticoagulants/pharmacology ; Thrombosis/drug therapy ; Peptides/pharmacology
    Chemical Substances Factor XIa (EC 3.4.21.27) ; Anticoagulants ; Peptides
    Language English
    Publishing date 2023-10-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120080-x
    ISSN 1090-2120 ; 0045-2068
    ISSN (online) 1090-2120
    ISSN 0045-2068
    DOI 10.1016/j.bioorg.2023.106951
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  7. Article ; Online: Macrocyclic factor XIa inhibitors.

    Wang, Cailan / Corte, James R / Rossi, Karen A / Bozarth, Jeffrey M / Wu, Yiming / Sheriff, Steven / Myers, Joseph E / Luettgen, Joseph M / Seiffert, Dietmar A / Wexler, Ruth R / Quan, Mimi L

    Bioorganic & medicinal chemistry letters

    2017  Volume 27, Issue 17, Page(s) 4056–4060

    Abstract: A series of macrocyclic factor XIa (FXIa) inhibitors was designed based on an analysis ...

    Abstract A series of macrocyclic factor XIa (FXIa) inhibitors was designed based on an analysis of the crystal structures of the acyclic phenylimidazole compounds. Further optimization using structure-based design led to inhibitors with pM affinity for FXIa, excellent selectivity against a panel of relevant serine proteases, and good potency in the activated partial thromboplastin time (aPTT) clotting assay.
    MeSH term(s) Dose-Response Relationship, Drug ; Factor XIa/antagonists & inhibitors ; Factor XIa/metabolism ; Humans ; Imidazoles/chemical synthesis ; Imidazoles/chemistry ; Imidazoles/pharmacology ; Macrocyclic Compounds/chemical synthesis ; Macrocyclic Compounds/chemistry ; Macrocyclic Compounds/pharmacology ; Molecular Structure ; Serine Proteinase Inhibitors/chemical synthesis ; Serine Proteinase Inhibitors/chemistry ; Serine Proteinase Inhibitors/pharmacology ; Structure-Activity Relationship
    Chemical Substances Imidazoles ; Macrocyclic Compounds ; Serine Proteinase Inhibitors ; imidazole (7GBN705NH1) ; Factor XIa (EC 3.4.21.27)
    Language English
    Publishing date 2017--01
    Publishing country England
    Document type Journal Article
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2017.07.048
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  8. Book: Du Xia

    Wang, Aihe

    (Wuming (No Name) Painting Catalogue : 无名画集 ; / Ed. by Wang Aihe[...])

    2010  

    Series title Wuming (No Name) Painting Catalogue : 无名画集
    / Ed. by Wang Aihe[...]
    Language Chinese ; English
    Size 120 p, Mostly ill.
    Publisher Hong Kong University Press
    Publishing place Hong Kong
    Document type Book
    ISBN 9789888028214 ; 9888028219
    Database Former special subject collection: coastal and deep sea fishing

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  9. Article ; Online: Generation of a human induced pluripotent stem cell line (FDCHi010-A) from a patient with Xia-Gibbs syndrome carrying AHDC1 mutation (c.2062C > T).

    Yin, Tingting / Wu, Bingbing / Peng, Ting / Liao, Yunfei / Jiao, Shuangyun / Wang, Huijun

    Stem cell research

    2023  Volume 69, Page(s) 103118

    Abstract: ... the pathogenesis and drug therapy screening of Xia-Gibbs syndrome caused by the AHDC1 gene. ...

    Abstract A human induced pluripotent stem cell line (iPSC), FDCHi010-A, was derived from the peripheral blood of a 3-year-old patient with the c.2062C > T (p.R688*) mutation in the AHDC1 gene. The established cell line displayed a typical human embryonic stem cell-like morphology, exhibited a normal euploid karyotype, and fully expressed pluripotency markers. In addition, it retained the ability to differentiate to three germ layers. This cell line with a specific mutation may provide a useful tool for studying the pathogenesis and drug therapy screening of Xia-Gibbs syndrome caused by the AHDC1 gene.
    MeSH term(s) Humans ; Child, Preschool ; Induced Pluripotent Stem Cells/metabolism ; Mutation/genetics ; Cell Line ; DNA-Binding Proteins/genetics
    Chemical Substances AHDC1 protein, human ; DNA-Binding Proteins
    Language English
    Publishing date 2023-05-06
    Publishing country England
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2393143-7
    ISSN 1876-7753 ; 1873-5061
    ISSN (online) 1876-7753
    ISSN 1873-5061
    DOI 10.1016/j.scr.2023.103118
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  10. Article ; Online: Discovery of Potent and Orally Bioavailable Pyridine N-Oxide-Based Factor XIa Inhibitors through Exploiting Nonclassical Interactions.

    Xu, Guozhang / Liu, Zhijie / Wang, Xinkang / Lu, Tianbao / DesJarlais, Renee L / Thieu, Tho / Zhang, Jing / Devine, Zheng Huang / Du, Fuyong / Li, Qiu / Milligan, Cynthia M / Shaffer, Paul / Cedervall, Peder E / Spurlino, John C / Stratton, Christopher F / Pietrak, Beth / Szewczuk, Lawrence M / Wong, Victoria / Steele, Ruth A /
    Bruinzeel, Wouter / Chintala, Madhu / Silva, Jose / Gaul, Michael D / Macielag, Mark J / Nargund, Ravi

    Journal of medicinal chemistry

    2022  Volume 65, Issue 15, Page(s) 10419–10440

    Abstract: Activated factor XI (FXIa) inhibitors are promising novel anticoagulants with low bleeding risk compared with current anticoagulants. The discovery of potent FXIa inhibitors with good oral bioavailability has been challenging. Herein, we describe our ... ...

    Abstract Activated factor XI (FXIa) inhibitors are promising novel anticoagulants with low bleeding risk compared with current anticoagulants. The discovery of potent FXIa inhibitors with good oral bioavailability has been challenging. Herein, we describe our discovery effort, utilizing nonclassical interactions to improve potency, cellular permeability, and oral bioavailability by enhancing the binding while reducing polar atoms. Beginning with literature-inspired pyridine N-oxide-based FXIa inhibitor
    MeSH term(s) Animals ; Anticoagulants/chemistry ; Anticoagulants/pharmacology ; Dogs ; Drug Design ; Factor XIa/metabolism ; Pyridines/pharmacology ; Rabbits ; Rats
    Chemical Substances Anticoagulants ; Pyridines ; pyridine N-oxide (91F12JJJ4H) ; Factor XIa (EC 3.4.21.27)
    Language English
    Publishing date 2022-07-21
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.2c00442
    Database MEDical Literature Analysis and Retrieval System OnLINE

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