Institution: | 1. University of Manchester, United Kingdom;2. AstraZeneca, United Kingdom;3. Sanofi, France;4. Simcyp Ltd., United Kingdom;5. Simulations Plus, Inc., United States;6. AbbVie, Germany;7. AstraZeneca, Sweden;8. AstraZeneca, United States;9. Bayer Pharma AG, Germany;10. Boehringer Ingelheim Pharma GmbH & Co. KG, Germany;11. GlaxoSmithKline, United Kingdom;12. Janssen, Belgium;13. Novartis, Switzerland;14. Pfizer, United Kingdom;15. Sanofi, United States;p. Sanofi, Germany;q. Uppsala University, Sweden |
Abstract: | Absorption of drugs is the first step after dosing, and it largely affects drug bioavailability. Hence, estimating the fraction of absorption (Fa) in humans is important in the early stages of drug discovery. To achieve correct exclusion of low Fa compounds and retention of potential compounds, we developed a freely available model to classify compounds into 3 levels of Fa capacity using only the chemical structure. To improve Fa prediction, we added predicted binary classification results of membrane permeability measured using Caco-2 cell line (Papp) and dried–dimethyl sulfoxide solubility (accuracy, 0.836; kappa, 0.560). The constructed models can be accessed via a web application. |