Development of an in silico model for human skin permeation based on a Franz cell skin permeability assay.
A multiple linear regression QSAR model was developed based on a set of 61 compounds with internally consistent permeability data measured across Franz cell. The data was normalized using a mean permeability value of a reference compound, 3-isobutyl-1-methylxanthine (IBMX). The QSAR model contained only five simple descriptors and had a correlation coefficient, r(2) of 0.77 between experimental and calculated values for skin permeability. The mean absolute error (MAE) was 0.3 for the entire set and the cross validation coefficient, q(2) was 0.71. The in silico skin permeability model was used as a filter for virtual libraries and to optimize skin permeation of specific compounds for several dermatology discovery projects.
Lee
Pil H
PH
Computer-Assisted Drug Discovery, Dynamics and Metabolism, Michigan Laboratories, Pfizer Global Research and Development, 2800 Plymouth Rd., Ann Arbor, MI 48105, United States.
Conradi
Robert
R
Shanmugasundaram
Veerabahu
V
D015056:1-Methyl-3-isobutylxanthine / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological; D021281:Quantitative Structure-Activity Relationship; D012869:Skin Absorption
D015056:1-Methyl-3-isobutylxanthine