In silico modeling of protein tyrosine phosphatase 1B inhibitors with cellular activity

Protein tyrosine phosphatase 1B (PTP1B) is a potential drug target for the treatment of Type 2 diabetes and obesity. The design of PTP1B inhibitors as therapeutic agents has been hampered mostly owing to their poor cell permeability and oral bioavailability. In the present study, we investigated the cellular activity of PTP1B inhibitors in relation to the 3D structure using classical VolSurf analysis. A model based on the VolSurf descriptors for a set of 80 compounds of PTP1B inhibitors, half of which display cellular activity, was analyzed using the principal components analysis (PCA) approach. The PCA model was applied to predict the cellular activities of an external data set of 40 PTP1B inhibitors and satisfactory results were obtained. Further partial least squares (PLS) analysis revealed useful information about the behavior of the Volsurf descriptors in predicting the cell permeability and pharmacokinetic properties of PTP1B inhibitors. In silico ADME studies provide a valuable tool in the development of effective PTP1B inhibitors as drug candidates.