computational prediction of blood-brain barrier permeability using decision tree induction血脑屏障通透性的计算预测使用决策树归纳.pdfVIP

Molecules 2012, 17, 10429-10445; doi:10.3390/molecules170910429 OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Computational Prediction of Blood-Brain Barrier Permeability Using Decision Tree Induction Claudia Suenderhauf 1, Felix Hammann 1,2 and Jörg Huwyler 1,* 1 Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland 2 Psychiatric Hospital of the University of Basel, Wilhelm-Klein-Str. 27, 4012 Basel, Switzerland * Author to whom correspondence should be addressed; E-Mail: joerg.huwyler@unibas.ch; Tel.: +41-61-267-15-00. Received: 8 June 2012; in revised form: 17 August 2012 / Accepted: 27 August 2012 / Published: 31 August 2012 Abstract: Predicting blood-brain barrier (BBB) permeability is essential to drug development, as a molecule cannot exhibit pharmacological activity within the brain parenchyma without first transiting this barrier. Understanding the process of permeation, however, is complicated by a combination of both limited passive diffusion and active transport. Our aim here was to establish predictive models for BBB drug permeation that include both active and passive transport. A database of 153 compounds was compiled using in vivo surface permeability product (logPS) values in rats as a quantitative parameter for BBB permeability. The open source Chemical Development Kit (CDK