Back to the future: can physical models of passive membrane permeability help reduce drug candidate attrition and move us beyond QSPR?

ABSTRACT: It is widely recognized that adsorption, distribution, metabolism, excretion, and toxicology liabilities kill the majority of drug candidates that progress to clinical trials. The development of computational models to predict small molecule membrane permeability is therefore of considerable scientific and public health interest. Empirical qualitative structure permeability relationship models of permeability have been a mainstay in industrial applications, but lack a deep understanding of the underlying biologic physics. Others and we have shown that implicit solvent models to predict passive permeability for small molecules exhibit mediocre predictive performance when validated across experimental test sets. Given the vast increase in computer power, more efficient parallelization scheme

SUBMITTER: Swift RV 

PROVIDER: S-EPMC3527668 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature