Fragment contribution models for predicting skin permeability using HuskinDB

Abstract

AbstractMathematical models to predict skin permeation tend to be based on animal derived experimental data as well as knowing physicochemical properties of the compound under investigation, such as molecular volume, polarity and lipophilicity. This paper presents a strikingly contrasting model to predict permeability, formed entirely from simple chemical fragment (functional group) data and a recently released, freely accessible human (i.e. non-animal) skin permeation database, known as the ‘Human Skin Database – HuskinDB’. Data from within the database allowed development of several fragment-based models, each including a calculable effect for all of the most commonly encountered functional groups present in compounds within the database. The developed models can be applied to predict human skin permeability (logKp) for any compound containing one or more of the functional groups analysed from the dataset with no need to know any other physicochemical properties, solely the type and number of each functional group within the chemical structure itself. This approach simplifies mathematical prediction of permeability for compounds with similar properties to those used in this study.