优化的阿里洛米辛是一种新的克拉姆阴性抗生素
Peter A Smith1, Michael F T Koehler2, Hany S Girgis3
1Department of Infectious Diseases, Genentech, South San Francisco, CA, USA. smith.peter@gene.com.
Nature
|September 14, 2018
概括
科学家们优化了天然产品阿里洛米辛, 制造出G0775, 一种有效的抗生素, 这种新药针对I型细菌信号酶,
科学领域:
- 微生物学
- 医学化学
- 药物发现
背景情况:
- 多种耐药性细菌,特别是格拉姆阴性病原体, 构成了全球健康的重大威胁.
- 在过去的50多年里,没有针对格拉姆阴性细菌的新类抗生素得到批准,这凸显了迫切需要新的治疗策略.
- 自然产品一直是抗生素开发的重要来源.
研究的目的:
- 在化学上优化具有有限光谱和活性的天然产品, 开发抗 Gram 阴性细菌的有效药物.
- 识别和描述新型抗生素对当代多抗药性临床隔离物的有效性.
- 探索抗生素对重要细菌点的新分子机制.
主要方法:
- 对自然产品的化学优化.
- 对包括多药耐药菌株在内的格兰阴性细菌组进行抗菌活性评估.
- 在体外和体内感染模型中评估疗效.
- 研究分子作用机制,重点是细菌I型信号酶抑制.
主要成果:
- 研发G0775,一种优化的阿里洛米辛类似物,具有强大,广泛的抗葛兰氏阴性细菌活性.
- 在实验室中,G0775对当前多药耐药的格拉姆阴性临床分离物有显著的疗效.
- 在几种体内模型中,该化合物成功治疗了感染.
- G0775通过一种前所未有的机制抑制了细菌I型信号酶,绕过了现有的抗药性途径.
结论:
- 像G0775这样的优化阿里洛米辛类药物代表了一种有前途的新型抗生素.
- G0775的新作用机制和广泛的活性为抗多药性格兰氏阴性感染提供了潜在的治疗策略.
- 进一步开发G0775可以解决对抗具有挑战性的细菌病原体的有效治疗的关键未满足需求.
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