A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules.
A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules.
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DOI：
10.1002/cmdc.201600182
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发表时间：
2016-06-06
期刊：
影响因子：
3.4
通讯作者：
Zoete, Vincent
中科院分区：
文献类型：
--
作者：
Daina, Antoine;Zoete, Vincent
关键词：
除了疗效和毒性外，许多药物开发失败可归因于不良的药代动力学和生物利用度。胃肠道吸收和大脑通路是药物发现过程中两个重要的药代动力学行为。为此，通过计算小分子的亲脂性和极性，脑或肠估计渗透方法（煮鸡蛋）被提出作为一种准确的预测模型。由于模型的速度、准确性、概念简单性和清晰的图形输出，大脑和肠道渗透的伴随预测都是由相同的两个物理化学描述符获得的，并直接转化为分子设计。从药物发现早期的化学文库过滤，到候选药物开发的评估，煮沸鸡蛋可以应用于各种环境中。
Apart from efficacy and toxicity, many drug development failures are imputable to poor pharmacokinetics and bioavailability. Gastrointestinal absorption and brain access are two pharmacokinetic behaviors crucial to estimate at various stages of the drug discovery processes. To this end, the Brain Or IntestinaL EstimateD permeation method (BOILED‐Egg) is proposed as an accurate predictive model that works by computing the lipophilicity and polarity of small molecules. Concomitant predictions for both brain and intestinal permeation are obtained from the same two physicochemical descriptors and straightforwardly translated into molecular design, owing to the speed, accuracy, conceptual simplicity and clear graphical output of the model. The BOILED‐Egg can be applied in a variety of settings, from the filtering of chemical libraries at the early steps of drug discovery, to the evaluation of drug candidates for development.
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