Ribeiro Eduarda, Vale Nuno
OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.
CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal.
Biomolecules. 2023 Aug 24;13(9):1296. doi: 10.3390/biom13091296.
Drug repurposing, also known as repositioning or reprofiling, has emerged as a promising strategy to accelerate drug discovery and development. This approach involves identifying new medical indications for existing approved drugs, harnessing the extensive knowledge of their bioavailability, pharmacokinetics, safety and efficacy. Levosimendan, a calcium sensitizer initially approved for heart failure, has been repurposed for oncology due to its multifaceted pharmacodynamics, including phosphodiesterase 3 inhibition, nitric oxide production and reduction of reactive oxygen species. Studies have demonstrated that levosimendan inhibits cancer cell migration and sensitizes hypoxic cells to radiation. Moreover, it exerts organ-protective effects by activating mitochondrial potassium channels. Combining levosimendan with traditional anticancer agents such as 5-fluorouracil (5-FU) has shown a synergistic effect in bladder cancer cells, highlighting its potential as a novel therapeutic approach. This drug repurposing strategy offers a cost-effective and time-efficient solution for developing new treatments, ultimately contributing to the advancement of cancer therapeutics and improved outcomes for patients. Further investigations and clinical trials are warranted to validate the effectiveness of levosimendan in oncology and explore its potential benefits in a clinical setting.
药物重新定位,也称为重新定向或重新剖析,已成为加速药物发现和开发的一种有前景的策略。这种方法涉及为现有已批准药物确定新的医学适应症,利用其关于生物利用度、药代动力学、安全性和有效性的广泛知识。左西孟旦,一种最初被批准用于治疗心力衰竭的钙敏化剂,由于其多方面的药效学特性,包括抑制磷酸二酯酶3、产生一氧化氮和减少活性氧,已被重新用于肿瘤学领域。研究表明,左西孟旦可抑制癌细胞迁移并使缺氧细胞对辐射敏感。此外,它通过激活线粒体钾通道发挥器官保护作用。将左西孟旦与传统抗癌药物如5-氟尿嘧啶(5-FU)联合使用已在膀胱癌细胞中显示出协同作用,突出了其作为一种新型治疗方法的潜力。这种药物重新定位策略为开发新疗法提供了一种经济高效且节省时间的解决方案,最终有助于推进癌症治疗并改善患者预后。有必要进行进一步的研究和临床试验,以验证左西孟旦在肿瘤学中的有效性,并探索其在临床环境中的潜在益处。