一种在Mycobacterium tuberculosis的ATP合成酶上活跃的二甲基氨酸药物
Koen Andries1, Peter Verhasselt, Jerome Guillemont
1Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium. kandries@prdbe.jnj.com
Science (New York, N.Y.)
|December 14, 2004
概括
一种名为R207910的新药对药物敏感性和耐药性结核病 (TB) 具有强烈活性. 这种二甲基诺林在小鼠中加速治疗,是新的结核病治疗的有希望的候选人.
科学领域:
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
- 传染性疾病 传染性疾病
背景情况:
- 全球结核病发病率正在上升.
- 40年来,没有开发出新的结核病药物.
- 耐药结核病对公众健康构成重大威胁.
研究的目的:
- 识别和描述具有针对Mycobacterium tuberculosis的活性的新型化合物.
- 在结核病的临床前模型中评估R207910的疗效.
- 评估R207910在人类志愿者中的安全性和耐受性.
主要方法:
- 在体外测试R207910对药物敏感性和耐药性Mycobacterium tuberculosis的敏感性.
- 在肺结核小鼠模型中的体内疗效研究.
- 在健康人体志愿者中进行的药理动力学和安全性评估.
- 在体外选择耐药突变物以阐明药物的作用机制.
主要成果:
- 在试验室中,R207910证明了对Mycobacterium结核病的强烈抑制 (MIC 0.06μg/ml).
- 在小鼠中,R207910与异化和利法相比,表现出更高的杀菌活性.
- 在一线治疗方案中用R207910替代加速了杀菌活性,并在一些组合中导致了完整的培养转换.
- 一次剂量的R207910在体内抑制了菌根菌的生长一周.
- 这种药物在有效剂量的健康志愿者中耐受性很好.
- 突变选择研究表明,R207910的目标是腺三酸盐 (ATP) 合成酶的质子.
结论:
- R207910是一种强效的新型二甲基诺林,具有显著的杀菌活性,用于对药物敏感和耐药结核病.
- R207910加速治疗,并显示出良好的安全性,使其成为新的结核病治疗的有希望的候选者.
- 鉴定R207910的作用机制为结核病药物开发提供了一个新的目标.
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