A Novel Approach for Predicting P-Glycoprotein (ABCB1) Inhibition Using Molecular Interaction Fields

• DOI: 10.1021/jm101421d
• Publication Date: 2011-02-22T16:43:32Z
• Authors: Fabio Broccatelli; Emanuele Carosati; Annalisa Neri; Maria Frosini; Laura Goracci; Tudor I. Oprea; Gabriele Cruciani
• Keywords: P-glycoprotein; Molecular model

P-glycoprotein (Pgp or ABCB1) is an ABC transporter protein involved in intestinal absorption, drug metabolism, and brain penetration, its inhibition can seriously alter a drug's bioavailability safety. In addition, inhibitors of Pgp be used to overcome multidrug resistance. Given this dual purpose, reliable silico procedures predict are great interest. A large accurate literature collection yielded more than 1200 structures; model was then constructed using various molecular interaction field-based technologies, considering pharmacophoric features those physicochemical properties related membrane partitioning. High accuracy demonstrated internally with two different validation sets and, moreover, number molecules, for which not experimentally available but evaluated in-house. All the validations confirmed robustness suitability help medicinal chemists discovery. The information derived from rationalized as pharmacophore competitive inhibition.