Drug Delivery, Disposition & Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
Future Med Chem. 2016 Jun;8(10):1017-25. doi: 10.4155/fmc-2016-0091. Epub 2016 Jun 21.
Polymyxins have emerged as an important last-line of defense against Gram-negative 'superbugs'. Unfortunately, the effective use of polymyxins in the clinic has been hampered by their nephrotoxic side effects. Over the last 10 years various industry and academic groups across the globe have been trying to develop new polymyxins that are safer and more efficacious than the currently approved polymyxin B and colistin. However these drug discovery programs are yet to deliver a new and improved polymyxin drug into the clinic. In this piece we provide an overview of the current state of these polymyxin drug discovery programs from a medicinal chemistry perspective as well as some thoughts on how future drug discovery efforts may ultimately find success.
多黏菌素已成为对抗革兰氏阴性“超级细菌”的重要最后防线。不幸的是，多黏菌素在临床上的有效应用受到其肾毒性副作用的阻碍。在过去的 10 年中，全球各地的各种行业和学术团体一直在努力开发比目前批准的多黏菌素 B 和黏菌素更安全、更有效的新多黏菌素。然而，这些药物发现计划尚未将一种新的改良多黏菌素药物推向临床。在这篇文章中，我们从药物化学的角度概述了这些多黏菌素药物发现计划的现状，并就未来的药物发现工作如何最终取得成功提出了一些看法。
