Structure-based systems biology for analyzing off-target binding.
Structure-based systems biology for analyzing off-target binding.
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DOI：
10.1016/j.sbi.2011.01.004
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发表时间：
2011-04
影响因子：
6.8
通讯作者：
Bourne PE
中科院分区：
文献类型：
--
作者：
Xie L;Xie L;Bourne PE
在此，脱靶结合意味着具有治疗意义的小分子与蛋白质靶标而非其预期的主要靶标的结合。尽管药物设计合理，但越来越多的这种脱靶似乎是常态而不是例外，并且可能导致有害的副作用，或者有机会重新定位治疗剂以治疗不同的病症。毫不奇怪，人们对先验确定全蛋白质组范围内存在哪些脱靶非常感兴趣。除了确定推定的脱靶之外，还需要了解这种结合对整个生物系统的影响，最终目标是能够预测表型结果。虽然这是一个雄心勃勃的目标，但正在取得一些进展。
Here off-target binding implies the binding of a small molecule of therapeutic interest to a protein target other than the primary target for which it was intended. Increasingly such off-targeting appears to be the norm rather than the exception, rational drug design notwithstanding, and can lead to detrimental side-effects, or opportunities to reposition a therapeutic agent to treat a different condition. Not surprisingly, there is significant interest in determining a priori what off-targets exist on a proteome-wide scale. Beyond determining putative off-targets is the need to understand the impact of such binding on the complete biological system, with the ultimate goal of being able to predict the phenotypic outcome. While a very ambitious goal, some progress is being made.