PMID: 11911703Mar 26, 2002Paper

Predicting Caco-2 cell permeation coefficients of organic molecules using membrane-interaction QSAR analysis

Journal of Chemical Information and Computer Sciences
A KulkarniAnton J Hopfinger

Abstract

A methodology termed membrane-interaction QSAR (MI-QSAR) analysis has been developed in order to predict the behavior of organic compounds interacting with the phospholipid-rich regions of biological membranes. One important application of MI-QSAR analysis is to estimate ADME properties including the transport of organic solutes through biological membranes as a computational approach to forecasting drug intestinal absorption. A training set of 30 structurally diverse drugs, whose permeability coefficients across the cellular membranes of Caco-2 cells were measured, was used to construct significant MI-QSAR models of Caco-2 cell permeation. Cellular permeation is found to depend primarily upon aqueous solvation free energy (solubility) of the drug, the extent of drug interaction with a model phospholipid (DMPC) monolayer, and the conformational flexibility of the solute within the model membrane. A test set of eight drugs was used to evaluate the predictivity of the MI-QSAR models. The permeation coefficients of the test set compounds were predicted with the same accuracy as the compounds of the training set.

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Citations

Jun 4, 2011·Journal of Molecular Modeling·Ranajit N ShindeM Elizabeth Sobhia
May 25, 2012·Journal of Chemical Information and Modeling·Siegfried S F LeungMatthew P Jacobson
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Nov 24, 2004·Journal of Chemical Information and Computer Sciences·Dahua PanAnton J Hopfinger

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