Jacob Golenser, Nicholas H. Hunt, Ida Birman, Charles L. Jaffe, Johanna Zech, Karsten Mäder, Daniel Gold
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引用次数: 0
摘要
对已获准用于人类的药物采用新的治疗适应症具有明显的优势,包括降低成本和缩短时间,因为不需要药物开发和监管的一些常规步骤。这项工作集中于青蒿素类药物(ARTS)的重新定向,这些药物已被批准用于疟疾的临床治疗,或正在对其进行研究。青蒿素类药物有几种作用机制,其中只有几种已在体内成功检验,主要是诱导氧化应激和抗炎作用。尽管这些作用看似相互矛盾,但 ARTS 仍被建议用于治疗炎症性疾病以及由病毒、细菌、真菌和寄生虫感染引起的各种类型的疾病。治疗病原体的预期结果是减少致病因子和/或其炎症损害。一般来说,ARTS 的再利用只有在极少数情况下才能取得成功,特别是当使用额外的治疗剂和适当的给药方式可以针对有效机制时。再利用研究应包括优化药物组合,然后在相关细胞系、有机体和动物模型中进行检查,最后再进行临床试验。
Applicability of Redirecting Artemisinins for New Targets
Employing new therapeutic indications for drugs that are already approved for human use has obvious advantages, including reduced costs and timelines, because some routine steps of drug development and regulation are not required. This work concentrates on the redirection of artemisinins (ARTS) that already are approved for clinical use, or investigated, for malaria treatment. Several mechanisms of action are suggested for ARTS, among which only a few have been successfully examined in vivo, mainly the induction of oxidant stress and anti-inflammatory effects. Despite these seemingly contradictory effects, ARTS are proposed for repurposing in treatment of inflammatory disorders and diverse types of diseases caused by viral, bacterial, fungal, and parasitic infections. When pathogens are treated the expected outcome is diminution of the causative agents and/or their inflammatory damage. In general, repurposing ARTS is successful in only a very few cases, specifically when a valid mechanism can be targeted using an additional therapeutic agent and appropriate drug delivery. Investigation of repurposing should include optimization of drug combinations followed by examination in relevant cell lines, organoids, and animal models, before moving to clinical trials.