Key Laboratory of Molecular Target & Clinical Pharmacology, State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital , Guangzhou Medical University , Guangzhou 511436 , P. R. China.
Division of Theoretical Chemistry and Biology, School of Biotechnology , Royal Institute of Technology (KTH) , AlbaNova University Center , Stockholm SE-100 44 , Sweden.
J Med Chem. 2019 Jul 11;62(13):5944-5978. doi: 10.1021/acs.jmedchem.8b01520. Epub 2019 Feb 12.
Chronic obstructive pulmonary disease (COPD) is a very common and frequently fatal airway disease. Current therapies for COPD depend mainly on long-acting bronchodilators, which cannot target the pathogenic mechanisms of chronic inflammation in COPD. New pharmaceutical therapies for the inflammatory processes of COPD are urgently needed. Several anti-inflammatory targets have been identified based on increased understanding of the pathogenesis of COPD, which raises new hopes for targeted treatment of this fatal respiratory disease. In this review, we discuss the recent advances in bioactive low-molecular-weight drugs (LMWDs) for the treatment of COPD and, in addition to the first-line drug bronchodilators, focus particularly on low-molecular-weight anti-inflammatory agents, including modulators of inflammatory mediators, inflammasome inhibitors, protease inhibitors, antioxidants, PDE4 inhibitors, kinase inhibitors, and other agents. We also provide new insights into targeted COPD treatments using LMWDs, particularly small-molecule agents.
慢性阻塞性肺疾病(COPD)是一种非常常见且经常致命的气道疾病。目前 COPD 的治疗主要依赖于长效支气管扩张剂,但这些药物并不能针对 COPD 慢性炎症的发病机制。因此,迫切需要针对 COPD 炎症过程的新药物疗法。基于对 COPD 发病机制的深入了解,已经确定了几种抗炎靶点,为这种致命性呼吸系统疾病的靶向治疗带来了新的希望。在这篇综述中,我们讨论了用于治疗 COPD 的生物活性低分子量药物(LMWD)的最新进展,除了一线药物支气管扩张剂外,我们还特别关注低分子量抗炎药物,包括炎症介质调节剂、炎症小体抑制剂、蛋白酶抑制剂、抗氧化剂、PDE4 抑制剂、激酶抑制剂和其他药物。我们还提供了使用 LMWD 进行靶向 COPD 治疗的新见解,特别是小分子药物。