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重新利用已批准用于心血管疾病的药物:机会还是幻影?

Repurposing of drugs approved for cardiovascular diseases: Opportunity or mirage?

机构信息

Department of Pharmaceutical Sciences, University of Milan, Milan, Italy.

Department of Pharmaceutical Sciences, University of Milan, Milan, Italy; Centro Cardiologico Monzino IRCCS, Milan, Italy.

出版信息

Biochem Pharmacol. 2020 Jul;177:113895. doi: 10.1016/j.bcp.2020.113895. Epub 2020 Mar 4.

Abstract

Drug repurposing is a promising way in drug discovery to identify new therapeutic uses -different from the original medical indication- for existing drugs. It has many advantages over traditional approaches to de novo drug discovery, since it can significantly reduce healthcare costs and development timeline. In this review, we discuss the possible repurposing of drugs approved for cardiovascular diseases, such as β-blockers, angiotensin converting enzyme inhibitors (ACE-Is), angiotensin II receptor blockers (ARBs), statins, aspirin, cardiac glycosides and low-molecular-weight heparins (LMWHs). Indeed, numerous experimental and epidemiological studies have reported promising anti-cancer activities for these drugs. It is worth mentioning, however, that the results of these studies are often controversial and very few data were obtained by controlled prospective clinical trials. Therefore, no final conclusion has yet been reached in this area and no final recommendations can be made. Moreover, β-blockers, ARBs and statins showed promising results in randomised controlled trials (RCTs) where pathological conditions other than cancer were considered. The results obtained have led or may lead to new indications for these drugs. For each drug or class of drugs, the potential molecular mechanisms of action justifying repurposing, results obtained in vitro and in animal models and data from epidemiological and randomized studies are described.

摘要

药物重定位是一种有前途的药物发现方法,可用于确定现有药物的新治疗用途(与原始医疗适应证不同)。与从头开始的新药发现传统方法相比,它具有许多优势,因为它可以显著降低医疗保健成本和开发时间。在这篇综述中,我们讨论了已批准用于心血管疾病的药物(如β受体阻滞剂、血管紧张素转换酶抑制剂(ACE-Is)、血管紧张素 II 受体阻滞剂(ARBs)、他汀类药物、阿司匹林、强心苷和低分子量肝素(LMWHs))的可能重定位。事实上,许多实验和流行病学研究报告了这些药物具有有希望的抗癌活性。值得一提的是,这些研究的结果往往存在争议,并且很少有数据是通过对照前瞻性临床试验获得的。因此,在这一领域尚未得出最终结论,也无法提出最终建议。此外,β受体阻滞剂、ARBs 和他汀类药物在考虑除癌症以外的病理状况的随机对照试验(RCT)中显示出有希望的结果。所获得的结果导致或可能导致这些药物的新适应证。对于每种药物或药物类别,描述了 justifies 重定位的潜在分子作用机制、在体外和动物模型中获得的结果以及来自流行病学和随机研究的数据。

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