Predicting efflux ratios and blood-brain barrier penetration from chemical structure: combining passive permeability with active efflux by P-glycoprotein.

ABSTRACT: In order to reach their pharmacologic targets, successful central nervous system (CNS) drug candidates have to cross a complex protective barrier separating brain from the blood. Being able to predict a priori which molecules can successfully penetrate this barrier could be of significant value in CNS drug discovery. Herein we report a new computational approach that combines two mechanism-based models, for passive permeation and for active efflux by P-glycoprotein, to provide insight into the multiparameter optimization problem of designing small molecules able to access the CNS. Our results indicate that this approach is capable of distinguishing compounds with high/low efflux ratios as well as CNS+/CNS- compounds and provides advantage over estimating P-glycoprotein efflux or passive pe

SUBMITTER: Dolghih E 

PROVIDER: S-EPMC3582291 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature