High confidence predictions of drug-drug interactions: predicting affinities for cytochrome P450 2C9 with multiple computational methods

Journal of Medicinal Chemistry
Matthew G HudelsonJeffrey P Jones

Abstract

Four different models are used to predict whether a compound will bind to 2C9 with a K(i) value of less than 10 microM. A training set of 276 compounds and a diverse validation set of 50 compounds were used to build and assess each model. The modeling methods are chosen to exploit the differences in how training sets are used to develop the predictive models. Two of the four methods develop partitioning trees based on global descriptions of structure using nine descriptors. A third method uses the same descriptors to develop local descriptions that relate activity to structures with similar descriptor characteristics. The fourth method uses a graph-theoretic approach to predict activity based on molecular structure. When all of these methods agree, the predictive accuracy is 94%. An external validation set of 11 compounds gives a predictive accuracy of 91% when all methods agree.

References

Aug 10, 2001·IEEE Engineering in Medicine and Biology Magazine : the Quarterly Magazine of the Engineering in Medicine & Biology Society·D J CookI Jonyer
Oct 2, 2002·Journal of Biomolecular Structure & Dynamics·Grazyna D Szklarz, Mark D Paulsen
Jul 23, 2003·Journal of Chemical Information and Computer Sciences·Roberta G Susnow, Steven L Dixon
Mar 27, 2004·Molecular Pharmacology·Leslie J DickmannAllan E Rettie
Jun 2, 2004·Biochemistry·Charles W LocusonJeffrey P Jones
Jun 8, 2004·The Journal of Biological Chemistry·Michael R WesterEric F Johnson
Feb 18, 2005·Journal of Medicinal Chemistry·Sean E O'Brien, Marcel J de Groot
Apr 12, 2005·Annual Review of Pharmacology and Toxicology·Allan E Rettie, Jeffrey P Jones
Jul 11, 2006·Journal of Medicinal Chemistry·Matthew G Hudelson, Jeffrey P Jones

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Citations

Aug 4, 2012·Journal of Chemical Information and Modeling·Yunierkis Pérez-CastilloAnn Nowé
Dec 5, 2008·Journal of Medicinal Chemistry·Chi-Chi PengJeffrey P Jones
Aug 15, 2014·Nature Protocols·Santiago VilarNicholas P Tatonetti
Feb 25, 2009·Expert Opinion on Drug Metabolism & Toxicology·Paul CzodrowskiThomas Fox
May 20, 2008·Expert Opinion on Drug Metabolism & Toxicology·Eva StjernschantzChris Oostenbrink
Nov 26, 2010·Expert Opinion on Drug Metabolism & Toxicology·Chao Xu, Donald E Mager
Jul 19, 2012·Molecular Systems Biology·Assaf GottliebRoded Sharan
May 24, 2011·Chemico-biological Interactions·Jeffrey P JonesDennis R Koop
Jan 25, 2019·Current Topics in Medicinal Chemistry·Alexander V DmitrievVladimir V Poroikov
Feb 2, 2017·Beilstein Journal of Organic Chemistry·Sumudu P Leelananda, Steffen Lindert
Feb 23, 2020·Healthcare Informatics Research·Selma Dere, Serkan Ayvaz
Mar 30, 2010·Archives of Biochemistry and Biophysics·Chi-Chi PengJeffrey P Jones

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