Abstract
This review focuses on both physicochemical and theoretical QSAR methods for the prediction of drug transport across the blood-brain barrier (BBB). Special emphasis is given to the recent progress that has been made in the modeling of BBB penetration, with a particular focus on the models based on kinetic parameters of BBB permeability dataset. Physicochemical models based on partition coefficients and chromatographic capacity factors, as well as computerized parameters such as polar surface area and hydrogenbonding descriptors are described and their success and limitations are discussed. Theoretical models based on topological or molecular orbital calculations are summarized and assessed in terms of descriptors, model type, predictive performance and interpretability. Strengths and weaknesses of the various methods are described. Related issues that are mentioned include the transporter-mediated permeation of drugs across the BBB and its implications on the stability and predictive quality of QSAR models.
Keywords: pharmacokinetic (PK) profiles, QSAR models, organic anion transporters (OATs), ABC-transporters, CNS, Diffusion
Current Computer-Aided Drug Design
Title: QSAR Studies on Blood-Brain Barrier Permeation
Volume: 2 Issue: 1
Author(s): Juan M. Luco and Eduardo Marchevsky
Affiliation:
Keywords: pharmacokinetic (PK) profiles, QSAR models, organic anion transporters (OATs), ABC-transporters, CNS, Diffusion
Abstract: This review focuses on both physicochemical and theoretical QSAR methods for the prediction of drug transport across the blood-brain barrier (BBB). Special emphasis is given to the recent progress that has been made in the modeling of BBB penetration, with a particular focus on the models based on kinetic parameters of BBB permeability dataset. Physicochemical models based on partition coefficients and chromatographic capacity factors, as well as computerized parameters such as polar surface area and hydrogenbonding descriptors are described and their success and limitations are discussed. Theoretical models based on topological or molecular orbital calculations are summarized and assessed in terms of descriptors, model type, predictive performance and interpretability. Strengths and weaknesses of the various methods are described. Related issues that are mentioned include the transporter-mediated permeation of drugs across the BBB and its implications on the stability and predictive quality of QSAR models.
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Cite this article as:
Luco M. Juan and Marchevsky Eduardo, QSAR Studies on Blood-Brain Barrier Permeation, Current Computer-Aided Drug Design 2006; 2 (1) . https://dx.doi.org/10.2174/157340906776056437
DOI https://dx.doi.org/10.2174/157340906776056437 |
Print ISSN 1573-4099 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6697 |
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