BDDCS 能否为药物设计照亮目标？
Can BDDCS illuminate targets in drug design?
机构信息
Translational Informatics Division, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
出版信息
Drug Discov Today. 2019 Dec;24(12):2299-2306. doi: 10.1016/j.drudis.2019.09.021. Epub 2019 Oct 1.
The fact that pharmacokinetic (PK) properties of drugs influence their interaction with protein targets is a principle known for decades. The same cannot be said for the opposite, namely that targets influence the PK properties of drugs. Evidence confirming this possibility is introduced here for the first time, as we show that certain protein families have a clear preference for drugs with specific PK properties. We investigate this by cross-referencing 'druggable target' annotations for >1000 US Food and Drug Administration (FDA)-approved drugs with their PK profile, as defined by the Biopharmaceutics Drug Disposition Classification System (BDDCS) criteria, and then examine the BDDCS preference for several major target protein families and therapeutic categories. Our findings suggest a novel way to conduct drug discovery by focusing PK profiles at the very early stage of target selection.
事实上，药物的药代动力学（PK）特性会影响其与蛋白靶标的相互作用，这一原理已经为人所知数十年。但与之相反的情况却并非如此，即靶标会影响药物的 PK 特性。本文首次引入了证实这种可能性的证据，因为我们表明某些蛋白家族显然更偏爱具有特定 PK 特性的药物。我们通过交叉引用超过 1000 种美国食品和药物管理局 (FDA) 批准药物的“可成药靶标”注释及其 PK 特征（根据生物药剂学药物处置分类系统 (BDDCS) 标准定义），并检查了 BDDCS 对几个主要靶标蛋白家族和治疗类别的偏好，来研究这一问题。我们的研究结果表明，通过在选择靶标早期就重点关注 PK 特征，可以为药物发现提供一种新方法。
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