Ma Zhenkun, Lynch Anthony Simon
TenNor Therapeutics Ltd. , 218 Xinghu Street, Suzhou Industrial Park, Suzhou 215123, China.
Janssen Research & Development LLC. , 1400 McKean Road, Spring House, Pennsylvania 18940, United States.
J Med Chem. 2016 Jul 28;59(14):6645-57. doi: 10.1021/acs.jmedchem.6b00485. Epub 2016 Jul 9.
The clinical management of prosthetic joint infections and other persistent bacterial infections represents a major unmet medical need. The rifamycins are one of the most potent antibiotic classes against persistent bacterial infections, but bacteria can develop resistance to rifamycins rapidly and the clinical utility of the rifamycin class is typically limited to antibiotic combinations to minimize the development of resistance. To develop a better therapy against persistent bacterial infections, a series of rifamycin based bifunctional molecules were designed, synthesized, and evaluated with the goal to identify a dual-acting drug that maintains the potent activity of rifamycins against persistent pathogens and at the same time minimize the development of rifamycin resistance. TNP-2092 was identified as a drug candidate and is currently in an early stage of clinical development for the treatment of prosthetic joint infections.
人工关节感染及其他持续性细菌感染的临床管理是一项尚未满足的重大医疗需求。利福霉素类是对抗持续性细菌感染最有效的抗生素类别之一，但细菌可迅速对利福霉素产生耐药性，且利福霉素类的临床应用通常限于抗生素联合使用，以尽量减少耐药性的产生。为开发更好的针对持续性细菌感染的治疗方法，设计、合成并评估了一系列基于利福霉素的双功能分子，目标是鉴定一种双效药物，既能保持利福霉素对持续性病原体的强效活性，又能同时尽量减少利福霉素耐药性的产生。TNP-2092被鉴定为候选药物，目前正处于治疗人工关节感染的临床开发早期阶段。
