Polymyxins: a new hope in combating Gram-negative superbugs?
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.
Drug Delivery, Disposition & Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
Tony
T
Velkov
Drug Delivery, Disposition & Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
Kade D
KD
Roberts
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
Philip E
PE
Thompson
Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, 19 Innovation Walk, Clayton 3800, Victoria, Australia.
Jian
J
Li
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002626:Chemistry, Pharmaceutical; D055808:Drug Discovery; D024901:Drug Resistance, Multiple, Bacterial; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D011113:Polymyxins / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
D000900:Anti-Bacterial Agents; D011113:Polymyxins
drug discovery; nephrotoxicity; polymyxins; resistance