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Artemisinin derivative SM934 in the treatment of autoimmune and inflammatory diseases: therapeutic effects and molecular mechanisms
Acta Pharmacologica Sinica ( IF 8.2 ) Pub Date : 2022-09-01 , DOI: 10.1038/s41401-022-00978-4
Xiao Tong 1, 2 , Li Chen 1, 2 , Shi-Jun He 1, 2 , Jian-Ping Zuo 1, 2
Affiliation  

Artemisinin and its derivatives are the well-known anti-malarial drugs derived from a traditional Chinese medicine. In addition to antimalarial, artemisinin and its derivatives possess distinguished anti-cancer, anti-oxidant, anti-inflammatory and anti-viral activities, but the poor solubility and low bioavailability hinder their clinical application. In the last decades a series of new water-soluble and oil-soluble derivatives were synthesized. Among them, we have found a water-soluble derivative β-aminoarteether maleate (SM934) that exhibits outstanding suppression on lymphocytes proliferation in immunosuppressive capacity and cytotoxicity screening assays with 35-fold higher potency than dihydroartemisinin. SM934 displays significant therapeutic effects on various autoimmune and inflammatory diseases, including systemic lupus erythematosus, antiphospholipid syndrome nephropathy, membranous nephropathy, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and dry eye disease. Here, we summarize the immunomodulatory effects, anti-inflammatory, anti-oxidative and anti-fibrosis activities of SM934 in disease-relevant animal models and present the probable pharmacological mechanisms involved in its therapeutic efficacy. This review also delineates a typical example of natural product-based drug discovery, which might further vitalize natural product exploration and development in pharmacotherapy.



中文翻译:

青蒿素衍生物 SM934 治疗自身免疫性疾病和炎症性疾病的疗效及分子机制

青蒿素及其衍生物是广为人知的抗疟疾药物,来源于传统中药。除抗疟疾外,青蒿素及其衍生物具有显着的抗癌、抗氧化、抗炎和抗病毒活性,但溶解度差和生物利用度低阻碍了其临床应用。在过去的几十年中,合成了一系列新的水溶性和油溶性衍生物。其中,我们发现了一种水溶性衍生物 β-氨基青蒿醚马来酸酯 (SM934),它在免疫抑制能力和细胞毒性筛选试验中表现出出色的淋巴细胞增殖抑制作用,效力比双氢青蒿素高 35 倍。SM934 对多种自身免疫性疾病和炎症性疾病具有显着的治疗作用,包括系统性红斑狼疮、抗磷脂综合征肾病、膜性肾病、类风湿性关节炎、多发性硬化症、炎症性肠病和干眼症。在这里,我们总结了 SM934 在疾病相关动物模型中的免疫调节作用、抗炎、抗氧化和抗纤维化活性,并介绍了其治疗功效可能涉及的药理学机制。这篇综述还描述了一个基于天然产物的药物发现的典型例子,这可能会进一步激发药物疗法中天然产物的探索和开发。SM934 在疾病相关动物模型中的抗氧化和抗纤维化活性,并介绍了其治疗功效中可能涉及的药理学机制。这篇综述还描述了一个基于天然产物的药物发现的典型例子,这可能会进一步激发药物疗法中天然产物的探索和开发。SM934 在疾病相关动物模型中的抗氧化和抗纤维化活性,并介绍了其治疗功效中可能涉及的药理学机制。这篇综述还描述了一个基于天然产物的药物发现的典型例子,这可能会进一步激发药物疗法中天然产物的探索和开发。

更新日期:2022-09-01
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