期刊
TRENDS IN PHARMACOLOGICAL SCIENCES
卷 37, 期 10, 页码 831-842出版社
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2016.06.008
关键词
-
资金
- Innovative Medicines Initiative Joint Undertaking (IMI JU) [115366]
- EU's Seventh Framework Programme
- European Federation of Pharmaceutical Industries and Associations (EFPIA)
It is generally accepted that, in conjunction with pharmacokinetics, the first order rate constant of target dissociation is a major determinant of the time course and duration of in vivo target occupancy. Here we show that the second order rate constant of target association can be equally important. On the basis of the commonly used mathematical models for drug target binding, it is shown that a high target association rate constant can increase the (local) concentration of the drug, which decreases the rate of decline of target occupancy. The increased drug concentration can also lead to increased off-target binding and decreased selectivity. Therefore, the kinetics of both target association and dissociation need to be taken into account in the selection of drug candidates with optimal pharmacodynamic properties.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据