Patrignani Paola, Contursi Annalisa, Tacconelli Stefania, Steinhilber Dieter
Systems Pharmacology and Translational Therapeutics Laboratory, The Center for Advanced Studies and Technology (CAST), "G. d' Annunzio" University, Chieti, Italy.
Department of Neuroscience, Imaging and Clinical Science, "G. d Annunzio" University Medical School, Chieti, Italy.
Front Pharmacol. 2024 Aug 29;15:1472396. doi: 10.3389/fphar.2024.1472396. eCollection 2024.
Many drugs can act on multiple targets or disease pathways, regardless of their original purpose. Drug repurposing involves reevaluating existing compounds for new medical uses. This can include repositioning approved drugs, redeveloping unapproved drugs, or repurposing any chemical, nutraceutical, or biotherapeutic product for new applications. Traditional drug development is slow, expensive, and has high failure rates. Drug repurposing can speed up the process, costing less and saving time. This approach can save 6-7 years of early-stage research time. Drug repurposing benefits from existing compounds with optimized structures and approved for clinical use with associated structure-activity relationship publications, supporting the development of new effective compounds. Drug repurposes can now utilize advanced screening enabled by artificial intelligence (AI) and sophisticated tissue and organ-level models. These models more accurately replicate human physiology and improve the selection of existing drugs for further pre-clinical testing and, eventually, clinical trials for new indications. This mini-review discusses some examples of drug repurposing and novel strategies for further development of compounds for targets of the arachidonic acid cascade. In particular, we will delve into the prospect of repurposing antiplatelet agents for cancer prevention and addressing the emerging noncanonical functionalities of 5-lipoxygenase, potentially for leukemia therapy.
许多药物可作用于多个靶点或疾病途径,无论其最初用途如何。药物重新利用涉及重新评估现有化合物的新医学用途。这可以包括重新定位已批准的药物、重新开发未批准的药物,或为新应用重新利用任何化学、营养保健品或生物治疗产品。传统的药物开发缓慢、昂贵且失败率高。药物重新利用可以加快这一过程,成本更低且节省时间。这种方法可以节省6至7年的早期研究时间。药物重新利用受益于具有优化结构且已获批临床使用并伴有相关构效关系出版物的现有化合物,有助于开发新的有效化合物。药物重新利用现在可以利用人工智能(AI)支持的先进筛选以及复杂的组织和器官水平模型。这些模型能更准确地复制人体生理学,并改进对现有药物的选择,以便进一步进行临床前测试,并最终用于新适应症的临床试验。这篇小型综述讨论了一些药物重新利用的例子以及用于进一步开发花生四烯酸级联反应靶点化合物的新策略。特别是,我们将深入探讨将抗血小板药物重新用于癌症预防的前景,以及解决5-脂氧合酶新出现的非经典功能,这可能用于白血病治疗。