Home Latest Articles
Latest Articles
  • Hui-jie DENG, Li LIANG, Yan CHEN, Yu-hang GUO, Jin-min GUO, Bing LI, Xiao-jian LIU
    Chinese Journal of New Drugs. 2023, 32(8): 858-864.
    Objective:

    To retrospectively analyze the cardiac adverse events and death cases of EGFR inhibitors through data mining of FDA adverse reaction reporting system (FAERS), so as to better understand the safety of EGFR inhibitors.

    Methods:

    The data in a total of 36 quarters in FAERS database from 2013 to 2021 were mined and analyzed by reporting odds ratio (ROR).

    Results:

    A total of 30 728 493 adverse events were reported in FAERS database from 2013 to 2021, including 735 693 cardiac adverse events. The effective signals were cetuximab [ROR=1.16, 95%CI (1.07,1.26)], rituximab [ROR=2.94, 95%CI (1.61,5.36)], dactinib [ROR=3.73, 95%CI (2.10,6.62)], and ositinib [ROR=1.55, 95%CI (1.44,1.66)]. McAbs were more likely to cause tachycardia. All heart-related effective signals of TKIs contained pericardial effusion. The significant death signals were panizumab [ROR=1.71, 95%CI (1.54,1.89)], gefitinib [ROR=2.93, 95%CI (2.64,3.25)], erlotinib [ROR=6.72, 95%CI (6.54,6.91)], afatinib [ROR=1.30, 95%CI(1.17,1.45)], dactinib [ROR=14.24, 95%CI (11.27,17.99)], and ositinib [ROR=15.03, 95%CI (14.53,15.54)].

    Conclusion:

    EGFR receptor inhibitors can cause adverse cardiac events with serious outcomes and increase the risk of death, which are worthy of clinical attention. Due to the limitations of database and detection methods, long-term data are still needed to verify these results to further understand the safety of EGFR inhibitors.

  • Jia-min ZHAO, Peng-gao CHENG, Wei DU, Na TANG, Dong WANG
    Chinese Journal of New Drugs. 2023, 32(8): 847-852.
    Objective:

    To determine the key influencing factors on formation of prasugrel hydrogen sulfate polymorph during the reactive crystallization of prasugrel free alkali and sulfuric acid, clarify the rule of the influences of solvent, temperature, and supersaturation, and reveal the mechanism of prasugrel hydrogen sulfate polymorph formation.

    Methods:

    Based on combined application of X-ray diffraction spectroscopy (PXRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), this study focused on the crystallization thermodynamics and reactive crystallization process of prasugrel hydrogen sulfate. The stability relationship between the polymorphs of prasugrel hydrogen sulfate and the influencing rule of polymorph formation during reaction crystallization were investigated.

    Results:

    It was shown that solvent and supersaturation were the key factors affecting the formation of prasugrel hydrogen sulfate polymorphs.

    Conclusion:

    Prasugrel hydrogen sulfate form Ⅰ and form Ⅱ are monotropically related systems, and form Ⅱ is a stable form. Solvent plays a leading role in the formation of prasugrel hydrogen sulfate polymorphs, and the formation of polymorphs in butanol obeys to the Ostwald's rule.

  • Jiao XUE, Qian CAO
    Chinese Journal of New Drugs. 2023, 32(8): 761-767.

    3CL protease is an ideal target for the research and development of anti-new coronavirus drugs. In this paper, the patent application situation of 3CL protease inhibitors in the field of anti-SARS-CoV-2 was analyzed. The focuses were put on the application time distribution, profile of patent applicants, and status of key products related to 3CL protease inhibitors, to reflect the global patent application trend, reveal the patent barriers faced by our country in the research and development of the drug, and provide support for the drug research and development. Combined with the results of patent analysis, this paper suggested that Chinese applicants expand their research and development ideas based on traditional Chinese medicine resources, and at the same time pay attention to the layout of overseas patents, and accelerate the in-depth integration of production, education, and research.

  • Zhi-yuan LIANG, Zhi-ying HUANG, Xing-chao GENG, Zhi LIN, Zhe QU
    Chinese Journal of New Drugs. 2023, 32(8): 787-792.

    Primary brain cancer is a heterogeneous group of tumors arising from cells within the central nervous system. The cure rate and survival period of patients with common malignant primary brain cancers are low, and their treatment methods and therapeutic effects are also quite limited. Therefore, it is necessary to construct appropriate tumor models to study the molecular biology of the disease, preclinical pharmacodynamic and safety evaluation of new anti-tumor drugs and/or the therapeutic methods. This review summarizes the research progress of in vitro and in vivo models of primary brain cancer. In vitro models mainly include the culture of brain cancer cell line, organoids and the brain slices. In vivo models mainly include the rodent models and other model organisms such as the fruit fly and zebrafish. At present, lots of primary brain cancer disease models with their own advantages and disadvantages have been developed, but these models cannot fully simulate the complexities of brain tumors in humans. Therefore, researchers are developing more complex disease models based on the existing models to study the primary brain tumor treatment methods, screen and evaluate therapeutic drugs.

  • Hui-ying WANG, Ai-nan ZHOU, Jian-wei WU, Peng XIE, Jian-qi LI
    Chinese Journal of New Drugs. 2023, 32(7): 676-686.

    At present, the listed antidepressants have certain limitations, and the different mechanisms of which are closely related to their efficacy and safety. Therefore, the discovery of antidepressants with novel mechanisms is an important research direction in the field of antidepressants. This paper reviews some major antidepressants currently under clinical research stage, and analyzes their mechanisms of action, so as to provide reference for the development of antidepressants with new mechanisms of action.

  • Yong-yi WANG, Lu HUANG, Cheng JIANG
    Chinese Journal of New Drugs. 2023, 32(7): 657-661.

    Daridorexant is a dual orexin receptor antagonist (DORA), which was approved by the U.S. FDA on January 10, 2022 (trade name: Quviviq) for the treatment of adults with insomnia, characterized by diffculties with sleep onset and/or sleep maintenance. Unlike traditional sedative-hypnotic drugs, daridorexant inhibits the actions of the wake-promoting orexin neuropeptides, by specific binding to both orexin receptor.In this paper, the mechanism of action, pharmacodynamics, pharmacokinetics, safety, and clinical research of daridorexant are reviewed.

  • Jue WU, Xu DU, Jing LIU, Hui JIANG, Yun SUN
    Chinese Journal of New Drugs. 2023, 32(7): 724-727.

    In the ethical review of the qualification of principal investigators, some problems such as insufficient certification materials to fully reflect the qualification of principal investigator, lack of qualification standard system of principal investigator, simple review method and single form, insufficient attention, weak awareness and low degree of independence were found. To further standardize the operation of the ethics committee and to improve the comprehensive review capacity, it is suggested to clearly specify the certification materials for qualification submission, building a comprehensive evaluation index system of qualification, taking a variety of review forms and strengthening the capacity-building of the ethics committee, so as to provide experience and reference.

  • Meng ZHENG, Yan WANG, Feng-qing FU, Li-yan MIAO
    Chinese Journal of New Drugs. 2023, 32(7): 687-694.

    Recently, radioimmunotherapy (RIT) has attracted much attention because of its precision targeted therapy. It is a therapeutic mode with great clinical application value to select an appropriate target molecule for radioimmunotherapy. B7-H3, also known as CD276, is an immune checkpoint molecule belonging to the B7 immunoglobin superfamily, which makes it an ideal candidate for RIT agents due to its unique expression characteristics and biological functions. Herein, we summarize the expression characteristics and biological functions of B7-H3. We also review the latest developments in radioimmunotherapy targeting B7-H3 in the context of cancer therapeutic.

  • Shuo QIN, Xiao-li DU
    Chinese Journal of New Drugs. 2023, 32(7): 662-665.

    Lonapegsomatropin-tcgd (tradename: SkytrofaTM) is the first long-acting new drug approved by FDA for the treatment of growth hormone deficiency in children. It can continuously release growth hormone and needs to be injected for only once a week. Lonapegsomatropin-tcpd improves patient compliance by reducing dosing frequency compared to traditional daily somatropin injection therapy. Clinical studies confirmed that weekly treatment of lonapegsomatropin-tcpd showed a higher annual growth velocity at week 52 compared with somatropin. In this article, the mechanism, pharmacokinetics, pharmacodynamics, clinical evaluation, safety, drug interaction and storage of lonapegsomatropin-tcpd are reviewed.

  • Jian ZHANG, Xiao-ke SHI, Zhong CHEN, Wen-jing XIAO, Yu-bo LI, Zai-yuan ZHANG, Dong-yi CAO, Fei WANG, Yong-he HU
    Chinese Journal of New Drugs. 2023, 32(7): 735-741.

    Objective: To investigate the mechanism of inhibitory effect of hydroxy-γ-isosanshool on estrogen synthesis in human ovarian granulosa cells.Methods:The effects of four kinds of sanshool on the proliferation of human ovarian granulosa cell line (KGN cell line) were detected by CCK-8. The effects of four kinds of sanshool on estradiol synthesis in KGN cells were detected by Elisa. Aromatase gene in KGN cells was detected by RT-qPCR, and aromatase protein and related pathway proteins were detected by Western Blot.Results:Hydroxy-γ-isosanshool had the strongest inhibitory effect on estradiol biosynthesis [IC50=(16.63±0.39) μmol·L-1], while had no significant inhibitory effect on the proliferation of KGN cells at the same concentration. The expression levels of aromatase gene and protein decreased significantly after the intervention of hydroxy-γ-isosanshool (P<0.05), and the activity of aromatase was not significantly affected. Hydroxy-γ-isosanshool significantly reduced the protein expressions of P-CERB, P-AKT and P-p38 (P<0.05).Conclusion:Hydroxy-γ-isosanshool may inhibit aromatase transcription and estrogen biosynthesis in KGN cells by inhibiting the activation of p38/MAPK and PI3K/AKT pathways and reducing the level of CREB phosphorylation, inhibit aromatase transcription, and ultimately inhibit the estrogen biosynthesis of KGN cells.