Development of a computational approach to predict blood-brain barrier permeability. Drug Metab Dispos 32:132–139.

Abstract

This article is available online at http://dmd.aspetjournals.org ABSTRACT: The objectives of this study were to generate a data set of bloodbrain barrier (BBB) permeability values for drug-like compounds and to develop a computational model to predict BBB permeability from structure. The BBB permeability, expressed as permeabilitysurface area product (PS, quantified as logPS), was determined for 28 structurally diverse drug-like compounds using the in situ rat brain perfusion technique. A linear model containing three descriptors, logD, van der Waals surface area of basic atoms, and polar surface area, was developed based on 23 compounds in our data set, where the penetration across the BBB was assumed to occur primarily by passive diffusion The blood-brain barrier (BBB 1 ) consists of a continuous layer of endothelial cells joined by tight junctions at the cerebral vasculature. It represents a physical and enzymatic barrier to restrict and regulate the penetration of compounds into and out of the brain and maintain the homeostasis of the brain microenvironmen