Kim Dahyun, Kim Young-Rok, Hwang Hee-Jong, Ciufolini Marco A, Lee Jusuk, Lee Hakyeong, Clovis Shyaka, Jung Sungji, Oh Sang-Hun, Son Young-Jin, Kwak Jin-Hwan
A&J Science Co., Ltd., 80 Chumbok Ro, Dong Gu, Daegu 41061, Korea.
School of Life Science, Handong Global University, 558 Handong Ro, Heunghae-Eup, Buk-Gu, Pohang 37554, Korea.
Pharmaceuticals (Basel). 2022 May 19;15(5):623. doi: 10.3390/ph15050623.
The US Centers for Disease Control and Prevention (CDC) lists as an urgent bacterial threat. Yet, only two drugs, vancomycin and fidaxomicin, are approved by the FDA for the treatment of infections as of this writing, while the global pipeline of new drugs is sparse at best. Thus, there is a clear and urgent need for new antibiotics against that organism. Herein, we disclose that AJ-024, a nitroimidazole derivative of a 26-membered thiopeptide, is a promising anti- lead compound. Despite their unique mode of action, thiopeptides remain largely unexploited as anti-infective agents. AJ-024 combines potent in vitro activity against various strains of with a noteworthy safety profile and desirable pharmacokinetic properties. Its time-kill kinetics against a hypervirulent ribotype 027 and in vivo (mouse) efficacy compare favorably to vancomycin, and they define AJ-024 as a valuable platform for the development of new anti- antibiotics.
美国疾病控制与预防中心（CDC）将其列为紧急细菌威胁。然而，截至撰写本文时，美国食品药品监督管理局（FDA）仅批准了两种药物，即万古霉素和非达霉素，用于治疗感染，而全球新药研发进展甚微。因此，迫切需要研发针对该病原体的新型抗生素。在此，我们披露AJ - 024，一种26元硫肽的硝基咪唑衍生物，是一种有前景的抗病原体先导化合物。尽管硫肽类具有独特的作用模式，但作为抗感染药物在很大程度上仍未得到充分利用。AJ - 024对多种病原体菌株具有强大的体外活性，同时具有良好的安全性和理想的药代动力学特性。其针对高毒力病原体核糖体分型027的杀菌动力学和体内（小鼠）疗效与万古霉素相比具有优势，这使AJ - 024成为开发新型抗病原体抗生素的宝贵平台。
