A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_F9348D9BBF74
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules.
Journal
ChemMedChem
Author(s)
Daina A., Zoete V.
ISSN
1860-7187 (Electronic)
ISSN-L
1860-7179
Publication state
Published
Issued date
06/06/2016
Peer-reviewed
Oui
Volume
11
Number
11
Pages
1117-1121
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.

Keywords
Biological Availability, Blood-Testis Barrier/metabolism, Brain/metabolism, Drug Design, Gastrointestinal Tract/metabolism, Humans, Models, Theoretical, Pharmaceutical Preparations/metabolism, Small Molecule Libraries/chemistry, Small Molecule Libraries/metabolism, blood-brain barrier, chemoinformatics, drug absorption, medicinal chemistry, physicochemical properties
Pubmed
Web of science
Open Access
Yes
Create date
05/02/2018 14:49
Last modification date
21/08/2019 7:11
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