title: A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules.
abstract: Apart from efficacy and toxicity, many drug development failures are imputable to poor pharmacokinetics and bioavailability. Gastrointestinal absorption and brain access are two pharmacokinetic behaviors crucial to estimate at various stages of the drug discovery processes. To this end, the Brain Or IntestinaL EstimateD permeation method (BOILED-Egg) is proposed as an accurate predictive model that works by computing the lipophilicity and polarity of small molecules. Concomitant predictions for both brain and intestinal permeation are obtained from the same two physicochemical descriptors and straightforwardly translated into molecular design, owing to the speed, accuracy, conceptual simplicity and clear graphical output of the model. The BOILED-Egg can be applied in a variety of settings, from the filtering of chemical libraries at the early steps of drug discovery, to the evaluation of drug candidates for development.
authors.affiliation: SIB Swiss Institute of Bioinformatics, Molecular Modeling Group, Quartier Sorge, Bâtiment Génopode, 1015, Lausanne, Switzerland.
authors.forename: Antoine
authors.initials: A
authors.lastname: Daina
authors.affiliation: SIB Swiss Institute of Bioinformatics, Molecular Modeling Group, Quartier Sorge, Bâtiment Génopode, 1015, Lausanne, Switzerland. vincent.zoete@sib.swiss.
authors.forename: Vincent
authors.initials: V
authors.lastname: Zoete
mesh_terms: D001682:Biological Availability; D001814:Blood-Testis Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D015195:Drug Design; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries
keywords: blood-brain barrier; chemoinformatics; drug absorption; medicinal chemistry; physicochemical properties