The potential for new and resilient anti-cancer drugs based upon minor groove binders for DNA
The potential for new and resilient anti-cancer drugs based upon minor groove binders for DNA
复制标题
DOI：
10.18103/mra.v9i11.2592
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Fraser J. Scott;C. Suckling
中科院分区：
文献类型：
--
作者：
Fraser J. Scott;C. Suckling
抗感染和抗癌药物都有一个严重的问题，即随着时间的推移，抗药性发展到它们的作用，导致临床过时。斯特拉斯克莱德大学的研究发现了一种基于DNA的微小沟槽结合物的抗感染药物平台，这种结合物对其目标生物体(细菌、真菌和寄生虫)的耐药性发展具有非凡的弹性。这一性质与斯特拉斯克莱德小沟槽粘结剂(S-MBBS)作用于不止一个离散的分子靶标的事实有关。其中一种化合物已经成功完成了治疗艰难梭状芽胞杆菌感染的IIa期临床试验。其他几种化合物在体外显示了对一些癌细胞的活性，并在小鼠肺癌模型中显示了体内活性。本文将这些发现放在先前关于小沟槽粘结剂作为抗癌剂的研究的背景下，并考虑在抗感染应用中成功展示的多靶向的好处是否可以转化为抗癌应用。
Anti-infective and anticancer drugs share the serious problem that over time resistance develops to their effects leading to clinical obsolescence. Research at the University of Strathclyde has discovered a platform of anti-infective drugs based upon minor groove binders for DNA that have exceptional resilience to the development of resistance in their target organisms (bacteria, fungi, and parasites). This property is associated with the fact that the Strathclyde minor groove binders (S-MGBs) act at more than one discrete molecular target. One of the compounds has successfully completed a phase IIa clinical trial for the treatment of Clostridioides difficile infections. Several other compounds have shown activity against a number of cancer cell lines in vitro with indications of in vivo activity in a mouse model of lung cancer. This paper places these discoveries in the context of previous studies of minor groove binders as anticancer agents and considers whether the benefits of multitargeting successfully demonstrated in anti-infective applications can be translated to anticancer applications.