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Rationally repurposed nitroxoline inhibits preclinical models of Epstein–Barr virus-associated lymphoproliferation
The Journal of Antibiotics ( IF 2.1 ) Pub Date : 2021-06-23 , DOI: 10.1038/s41429-021-00433-2
Maite Ibáñez de Garayo 1, 2 , Wendi Liu 3 , Nicole C Rondeau 1 , Christopher B Damoci 3 , J J L Miranda 1
Affiliation  

Repurposing of currently used drugs for new indications benefits from known experience with those agents. Rational repurposing can be achieved when newly uncovered molecular activities are leveraged against diseases that utilize those mechanisms. Nitroxoline is an antibiotic with metal-chelating activity used to treat urinary tract infections. This small molecule also inhibits the function of bromodomain and extraterminal (BET) proteins that regulate oncogene expression in cancer. Lymphoproliferation driven by the Epstein–Barr virus (EBV) depends on these same proteins. We therefore tested the efficacy of nitroxoline against cell culture and small animal models of EBV-associated lymphoproliferation. Nitroxoline indeed reduces cell and tumor growth. Nitroxoline also acts faster than the prototype BET inhibitor JQ1. We suggest that this rational repurposing may hold translational promise.



中文翻译:

合理改变用途的硝唑啉抑制 EB 病毒相关淋巴细胞增殖的临床前模型

将目前使用的药物重新用于新的适应症受益于这些药物的已知经验。当新发现的分子活动被用于对抗利用这些机制的疾病时,可以实现合理的再利用。Nitroxoline 是一种具有金属螯合活性的抗生素,用于治疗尿路感染。这种小分子还抑制调节癌症癌基因表达的溴结构域和末端外 (BET) 蛋白的功能。爱泼斯坦-巴尔病毒 (EBV) 驱动的淋巴细胞增殖依赖于这些相同的蛋白质。因此,我们测试了硝唑啉对 EBV 相关淋巴增殖的细胞培养和小动物模型的功效。Nitroxoline 确实可以减少细胞和肿瘤的生长。Nitroxoline 的作用也比原型 BET 抑制剂 JQ1 更快。

更新日期:2021-06-23
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