• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
YAN Pei, YE Lianbao, CHEN Weiqiang. Progress in therapeutic targets and development of drugs against chronic obstructive pulmonary disease[J]. Journal of China Pharmaceutical University, 2021, 52(2): 144-155. DOI: 10.11665/j.issn.1000-5048.20210202
Citation: YAN Pei, YE Lianbao, CHEN Weiqiang. Progress in therapeutic targets and development of drugs against chronic obstructive pulmonary disease[J]. Journal of China Pharmaceutical University, 2021, 52(2): 144-155. DOI: 10.11665/j.issn.1000-5048.20210202

Progress in therapeutic targets and development of drugs against chronic obstructive pulmonary disease

Funds: This study was supported by Guangdong Provincial Department of Education New Generation Information Technology Key Field Special Project (No.2020ZDZX3026)
More Information
  • Received Date: April 30, 2020
  • Revised Date: March 06, 2021
  • Chronic obstructive pulmonary disease (COPD), characterized by airflow constraint, is a chronic respiratory disease closely related to the chronic inflammatory response of the airways and lungs to harmful gases or toxic particles, which may further develop into pulmonary heart disease and respiratory failure.At present the complex pathogenesis of COPD is considered to be the result of the interaction of a variety of genetic and environmental factors, and there is stiu no safe and effective drug for the treatment. This article reviews the pathogenesis of COPD from such aspects as oxidative stress, protease/antiprotease imbalance, immune mechanism, cell aging and cell repair mechanism, cell necrosis and autophagy,withan introduction to the potential targets and clinical research progress of related drugs, including β2 receptor agonists, muscarinic antagonists, theophylline and its derivatives, drugs targeting inflammatory mediators, protease inhibitors, kinase inhibitors, PED4 inhibitors, glandular glycoside receptor modulators,and antioxidants, which may provide some reference for the development of new drugs for COPD.
  • [1]
    . Respirology, 2016, 21(1): 14-23.
    [2]
    Hogg JC. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease [J]. Lancet, 2004, 364(9435): 709-721.
    [3]
    Peiffer G, Underner M, Perriot J. Les effets respiratoires du tabagisme (The respiratory effects of smoking)[J]. Rev Pneumol Clin, 2018, 74(3): 133-144.
    [4]
    Toledo-Pons N, Cosío BG, Velasco MD. Chronic obstructive pulmonary disease in non-smokers [J]. Arch Bronconeumol, 2017, 53(2): 45-46.
    [5]
    Corhay JL, Frusch N, Louis R. Interrelations génétique-environnement: la broncho-pneumopathie chronique obstructive [COPD: genetics and environmental interactions] [J]. Rev Med Liege, 2012, 67(5-6): 292-297.
    [6]
    Raghavan D, Varkey A, Bartter T. Chronic obstructive pulmonary disease: the impact of gender [J]. Curr Opin Pulm Med, 2017, 23(2): 117-123.
    [7]
    Cortopassi F, Gurung P, Pinto-Plata V. Chronic obstructive pulmonary disease in elderly patients [J]. Clin Geriatr Med, 2017, 33(4): 539-552.
    [8]
    Postma DS, Bush A, van den Berge M. Risk factors and early origins of chronic obstructive pulmonary disease [J]. Lancet, 2015, 385(9971): 899-909.
    [9]
    McGuinness AJ, Sapey E. Oxidative stress in COPD: sources, markers, and potential mechanisms [J]. J Clin Med, 2017, 6(2): 21.
    [10]
    Stockley RA. Neutrophils and protease/antiprotease imbalance [J]. Am J Respir Crit Care Med, 1999, 160(5 Pt 2): S49-52.
    [11]
    Pauwels NS, Bracke KR, Dupont LL, et al. Role of IL-1α and the Nlrp3/caspase-1/IL-1β axis in cigarette smoke-induced pulmonary inflammation and COPD [J]. Eur Respir J, 2011, 38(5): 1019-1028.
    [12]
    Qiu SL, Zhang H, Tang QY, et al. Neutrophil extracellular traps induced by cigarette smoke activate plasmacytoid dendritic cells [J]. Thorax, 2017, 72(12): 1084-1093.
    [13]
    Jiang B, Guan Y, Shen HJ, et al. Akt/PKB signaling regulates cigarette smoke-induced pulmonary epithelial-mesenchymal transition [J]. Lung Cancer, 2018, 122: 44-53.
    [14]
    Eapen MS, Sharma P, Gaikwad AV, et al. Epithelial-mesenchymal transition is driven by transcriptional and post transcriptional modulations in COPD: implications for disease progression and new therapeutics [J]. Int J Chron Obstruct Pulmon Dis, 2019, 14: 1603-1610.
    [15]
    Barnes PJ. Senescence in COPD and its comorbidities [J]. Annu Rev Physiol, 2017, 79: 517-539.
    [16]
    Mercado N, Ito K, Barnes PJ. Accelerated ageing of the lung in COPD: new concepts [J]. Thorax, 2015, 70(5): 482-489.
    [17]
    Ghosh M, Miller YE, Nakachi I, et al. Exhaustion of airway basal progenitor cells in early and established chronic obstructive pulmonary disease [J]. Am J Respir Crit Care Med, 2018, 197(7): 885-896.
    [18]
    Galluzzi L, Vitale I, Aaronson SA, et al. Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018 [J]. Cell Death Differ, 2018, 25(3): 486-541.
    [19]
    Pouwels SD, Zijlstra GJ, van der Toorn M, et al. Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway inflammation in mice [J]. Am J Physiol Lung Cell Mol Physiol, 2016, 310(4): L377-386.
    [20]
    Wang Y, Zhou JS, Xu XC, et al. Endoplasmic reticulum chaperone GRP78 mediates cigarette smoke-induced necroptosis and injury in bronchial epithelium [J]. Int J Chron Obstruct Pulmon Dis, 2018, 13: 571-581.
    [21]
    Leermakers PA, AMWJSchols, Kneppers AEM, et al. Molecular signalling towards mitochondrial breakdown is enhanced in skeletal muscle of patients with chronic obstructive pulmonary disease (COPD) [J]. Sci Rep, 2018, 8(1): 15007.
    [22]
    Billington CK, Penn RB, Hall IP. β (2) agonists [J]. Handb Exp Pharmacol, 2017, 237: 23-40.
    [23]
    Williams DM, Rubin BK. Clinical pharmacology of bronchodilator medications [J]. Respir Care, 2018, 63(6): 641-654.
    [24]
    Yamada M, Ichinose M. The cholinergic pathways in inflammation: a potential pharmacotherapeutic target for COPD [J]. Front Pharmacol, 2018, 9: 1426.
    [25]
    Vogelmeier CF, Bateman ED, Pallante J, et al. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group study [J]. Lancet Respir Med, 2013, 1(1): 51-60.
    [26]
    Barnes PJ. Theophylline [J]. Am J Respir Crit Care Med, 2013, 188(8): 901-906.
    [27]
    Lazaar AL, Sweeney LE, MacDonald AJ, et al. A novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans [J]. Br J Clin Pharmacol, 2011, 72(2): 282-293.
    [28]
    Churg A, Wang R, Wang X, et al. Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs [J]. Thorax, 2007, 62(8): 706-713.
    [29]
    Barnes PJ. Kinases as novel therapeutic targets in asthma and chronic obstructive pulmonary disease [J]. Pharmacol Rev, 2016, 68(3): 788-815.
    [30]
    Doukas J, Eide L, Stebbins K, et al. Aerosolized phosphoinositide 3-kinase gamma/delta inhibitor TG100-115 [3-[2,4-diamino-6-(3-hydroxyphenyl)pteridin-7-yl]phenol] as a therapeutic candidate for asthma and chronic obstructive pulmonary disease [J]. J Pharmacol Exp Ther, 2009, 328(3): 758-765.
    [31]
    Erra M, Taltavull J, Gréco A, et al. Discovery of a potent, selective, and orally available PI3Kδ inhibitor for the treatment of inflammatory diseases [J]. ACS Med Chem Lett, 2016, 8(1): 118-123.
    [32]
    Fenwick PS, Macedo P, Kilty IC, et al. Effect of JAK inhibitors on release of CXCL9, CXCL10 and CXCL11 from human airway epithelial cells [J]. PLoS One, 2015, 10(6): e0128757.
    [33]
    Hegab AE, Sakamoto T, Nomura A, et al. Niflumic acid and AG-1478 reduce cigarette smoke-induced mucin synthesis: the role of hCLCA1 [J]. Chest, 2007, 131(4): 1149-1156.
    [34]
    Chong J, Leung B, Poole P. Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease [J]. Cochrane Database Syst Rev, 2017, 9(9): Cd002309.
    [35]
    Watz H, Mistry SJ, Lazaar AL. Safety and tolerability of the inhaled phosphodiesterase 4 inhibitor GSK256066 in moderate COPD [J]. Pulm Pharmacol Ther, 2013, 26(5): 588-595.
    [36]
    Yang Q, Wu FR, Wang JN, et al. Nox4 in renal diseases: an update [J]. Free Radic Biol Med, 2018, 124: 466-472.
    [37]
    Laleu B, Gaggini F, Orchard M, et al. First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis [J]. J Med Chem, 2010, 53(21): 7715-7730.
    [38]
    Soubhye J, Chikh Alard I, Aldib I, et al. Discovery of novel potent reversible and irreversible myeloperoxidase inhibitors using virtual screening procedure [J]. J Med Chem, 2017, 60(15): 6563-6586.
  • Related Articles

    [1]ZHU Enni, WU Chaoran, LIAO Hong. Research progress of metabotropic glutamate receptor 5 in related central nervous system diseases[J]. Journal of China Pharmaceutical University, 2021, 52(6): 751-758. DOI: 10.11665/j.issn.1000-5048.20210614
    [2]WEI Yuanyuan, YANG Fan, TANG Jie, YU Lifang. Advances in the research of anti-tuberculosis drugs[J]. Journal of China Pharmaceutical University, 2020, 51(2): 231-239. DOI: 10.11665/j.issn.1000-5048.20200215
    [3]YIN Kunpeng, ZHENG Hao, XIE Binxin, LI Ping, ZHANG Lei, FAN Yong, ZHU Wei, QI Lianwen. Clinical metabolomics in diagnosis and therapy of coronary artery disease[J]. Journal of China Pharmaceutical University, 2017, 48(6): 629-634. DOI: 10.11665/j.issn.1000-5048.20170601
    [4]YANG Ruocong, DUAN Feipeng, CHAO Jiahong, TIAN Pengpeng, YAN Zhiyong, LI Shaojing. Advances of microRNA activity in innate immunity[J]. Journal of China Pharmaceutical University, 2017, 48(4): 396-406. DOI: 10.11665/j.issn.1000-5048.20170403
    [5]JIANG Lu, CHEN Dandan, SUN Minjie, PING Qineng, ZHANG Can. Advances of wax matrix tablets[J]. Journal of China Pharmaceutical University, 2016, 47(4): 497-502. DOI: 10.11665/j.issn.1000-5048.20160418
    [6]YAO Guilin, WANG Haiyong, LU Tao. Advances of the uricosuric drugs[J]. Journal of China Pharmaceutical University, 2016, 47(4): 491-496. DOI: 10.11665/j.issn.1000-5048.20160417
    [7]WU Weixin, YAN Jia, TAN Xiying, LI Bo, SU Mengxiang, YAN Fang, DI Bin. Advances in enrichment strategies for phosphoproteomics and its application in the research of disease[J]. Journal of China Pharmaceutical University, 2016, 47(1): 19-29. DOI: 10.11665/j.issn.1000-5048.20160103
    [8]YIN Lei, WANG Ying, CHEN Song, GAO Xiangdong. Advances of glucagon-like peptide-1 receptor agonists in the treatment of nervous system diseases[J]. Journal of China Pharmaceutical University, 2014, 45(4): 383-391. DOI: 10.11665/j.issn.1000-5048.20140401
    [9]DENG Danni, TIAN Hong, YAO Wenbing. Advances in therapeutic B-cell vaccines against chronic diseases[J]. Journal of China Pharmaceutical University, 2013, 44(5): 470-475. DOI: 10.11665/j.issn.1000-5048.20130517
    [10]XU Si-sheng, ZHANG Hui-bin, ZHOU Jin-pei, HUANG Jian-jun. Advances of new antidiabetic drugs[J]. Journal of China Pharmaceutical University, 2011, 42(2): 97-106.
  • Cited by

    Periodical cited type(17)

    1. 孙佳乐,崔雅璇,张新征,李群. 无创正压通气与经鼻高流量氧疗治疗慢性阻塞性肺疾病急性加重期轻度呼吸衰竭患者的疗效观察. 实用医院临床杂志. 2024(01): 68-71 .
    2. 卢丽君,田辉,郑洋,胡汉姣. 紫花牡荆素对脂多糖诱导的BEAS-2B细胞损伤和NF-κB-Keap1-Nrf2/ARE通路的影响. 中国免疫学杂志. 2024(03): 546-550 .
    3. 黄武祯,陈斯宁,黎展华. 利金方治疗慢性阻塞性肺疾病的作用机制探析. 今日药学. 2024(08): 636-640 .
    4. 薛晴,杨美玲,刘岩明. 比较不同剂量沙美特罗替卡松粉在治疗中重度稳定型慢性阻塞性肺疾病疗效. 罕少疾病杂志. 2024(10): 33-35 .
    5. 赵萌,赵育周,赵志娟,霍树芬. T淋巴细胞亚群在慢性阻塞性肺疾病发生、发展中的作用研究进展. 检验医学与临床. 2023(05): 705-709 .
    6. 葛进男,张晓风,葛蕾蕾,许晓霞. 早期肺康复对慢性阻塞性肺疾病急性加重期患者的影响. 当代护士(中旬刊). 2023(03): 27-30 .
    7. 张文硕,吴常柱. 无创呼吸机联合沙丁胺醇治疗慢性阻塞性肺疾病并发呼吸衰竭的效果及对炎症因子的影响. 系统医学. 2023(06): 19-23 .
    8. 郭春明,江露,范有明. 慢性阻塞性肺疾病中西医结合治疗研究进展. 中国药物经济学. 2023(07): 108-113 .
    9. 冷安明,杨静,张葵. 桑色素通过抑制MMP9表达改善慢性阻塞性肺疾病. 安徽医科大学学报. 2023(12): 1987-1994 .
    10. 刘海波,张敬敏,刘秀兰,王锋,刘明月,李建玲. 驱动压肺保护性通气策略对慢性阻塞性肺疾病大鼠呼吸功能和血液动力学的影响. 医学研究与战创伤救治. 2023(12): 1242-1249 .
    11. 贾健,吴建兵,张奕华,黄张建. 羧甲司坦L-精氨酸盐的合成及其对支气管上皮细胞的保护作用. 中国药科大学学报. 2022(02): 171-177 . 本站查看
    12. 韩雪,王婷婷,王惠琴. 沙丁胺醇联合布地奈德雾化吸入对慢性阻塞性肺疾病急性加重期患者气道重塑、炎症介质水平的影响. 临床医学研究与实践. 2022(17): 70-74 .
    13. 李明明,宋堃,王亚威. 基于PERMA模式的优质护理在老年慢阻肺患者中的应用观察. 包头医学. 2022(01): 54-56 .
    14. 陈建平,黄坤,牛犇. Boehringer Ingelheim关于噻托溴铵的工艺研究进展. 化工管理. 2022(24): 65-67 .
    15. 田晨,刘志辉,孟繁荣,李华,何湘蓉,胡锦兴. 香烟烟雾提取物诱导16HBE细胞MUC5AC上调的机制. 实用医学杂志. 2022(18): 2309-2317 .
    16. 高文. 辛伐他汀与雷芬那辛治疗慢性阻塞性肺疾病临床疗效及对肺循环阻力的影响对比. 基层医学论坛. 2022(31): 35-38 .
    17. 孙宁,于文晓,袁芳. 基于网络药理学和分子对接技术探讨桑梅止咳颗粒治疗COPD的作用机制. 湖南中医药大学学报. 2021(12): 1905-1913 .

    Other cited types(15)

Catalog

    Article views (923) PDF downloads (1402) Cited by(32)

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return