Literature DB >> 26199424

Making Transporter Models for Drug-Drug Interaction Prediction Mobile.

Sean Ekins1, Alex M Clark2, Stephen H Wright2.   

Abstract

The past decade has seen increased numbers of studies publishing ligand-based computational models for drug transporters. Although they generally use small experimental data sets, these models can provide insights into structure-activity relationships for the transporter. In addition, such models have helped to identify new compounds as substrates or inhibitors of transporters of interest. We recently proposed that many transporters are promiscuous and may require profiling of new chemical entities against multiple substrates for a specific transporter. Furthermore, it should be noted that virtually all of the published ligand-based transporter models are only accessible to those involved in creating them and, consequently, are rarely shared effectively. One way to surmount this is to make models shareable or more accessible. The development of mobile apps that can access such models is highlighted here. These apps can be used to predict ligand interactions with transporters using Bayesian algorithms. We used recently published transporter data sets (MATE1, MATE2K, OCT2, OCTN2, ASBT, and NTCP) to build preliminary models in a commercial tool and in open software that can deliver the model in a mobile app. In addition, several transporter data sets extracted from the ChEMBL database were used to illustrate how such public data and models can be shared. Predicting drug-drug interactions for various transporters using computational models is potentially within reach of anyone with an iPhone or iPad. Such tools could help prioritize which substrates should be used for in vivo drug-drug interaction testing and enable open sharing of models.
Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

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Year:  2015        PMID: 26199424      PMCID: PMC4576675          DOI: 10.1124/dmd.115.064956

Source DB:  PubMed          Journal:  Drug Metab Dispos        ISSN: 0090-9556            Impact factor:   3.922


  25 in total

1.  Open Source Bayesian Models. 2. Mining a "Big Dataset" To Create and Validate Models with ChEMBL.

Authors:  Alex M Clark; Sean Ekins
Journal:  J Chem Inf Model       Date:  2015-06-03       Impact factor: 4.956

2.  Why we should be vigilant: drug cytotoxicity observed with in vitro transporter inhibition studies.

Authors:  Xiaowan Zheng; Lei Diao; Sean Ekins; James E Polli
Journal:  Biochem Pharmacol       Date:  2010-06-23       Impact factor: 5.858

3.  The ChEMBL database: a taster for medicinal chemists.

Authors:  George Papadatos; John P Overington
Journal:  Future Med Chem       Date:  2014-03       Impact factor: 3.808

4.  Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling.

Authors:  Matthias B Wittwer; Arik A Zur; Natalia Khuri; Yasuto Kido; Alan Kosaka; Xuexiang Zhang; Kari M Morrissey; Andrej Sali; Yong Huang; Kathleen M Giacomini
Journal:  J Med Chem       Date:  2013-01-22       Impact factor: 7.446

5.  Structure-activity relationship for FDA approved drugs as inhibitors of the human sodium taurocholate cotransporting polypeptide (NTCP).

Authors:  Zhongqi Dong; Sean Ekins; James E Polli
Journal:  Mol Pharm       Date:  2013-02-12       Impact factor: 4.939

6.  Computational models for drug inhibition of the human apical sodium-dependent bile acid transporter.

Authors:  Xiaowan Zheng; Sean Ekins; Jean-Pierre Raufman; James E Polli
Journal:  Mol Pharm       Date:  2009 Sep-Oct       Impact factor: 4.939

7.  Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions.

Authors:  Alexander Sedykh; Denis Fourches; Jianmin Duan; Oliver Hucke; Michel Garneau; Hao Zhu; Pierre Bonneau; Alexander Tropsha
Journal:  Pharm Res       Date:  2012-12-27       Impact factor: 4.200

8.  Quantitative NTCP pharmacophore and lack of association between DILI and NTCP Inhibition.

Authors:  Zhongqi Dong; Sean Ekins; James E Polli
Journal:  Eur J Pharm Sci       Date:  2014-09-16       Impact factor: 4.384

9.  Open Source Bayesian Models. 1. Application to ADME/Tox and Drug Discovery Datasets.

Authors:  Alex M Clark; Krishna Dole; Anna Coulon-Spektor; Andrew McNutt; George Grass; Joel S Freundlich; Robert C Reynolds; Sean Ekins
Journal:  J Chem Inf Model       Date:  2015-06-03       Impact factor: 4.956

10.  New target prediction and visualization tools incorporating open source molecular fingerprints for TB Mobile 2.0.

Authors:  Alex M Clark; Malabika Sarker; Sean Ekins
Journal:  J Cheminform       Date:  2014-08-04       Impact factor: 5.514

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  8 in total

1.  Lack of Influence of Substrate on Ligand Interaction with the Human Multidrug and Toxin Extruder, MATE1.

Authors:  Lucy J Martínez-Guerrero; Mark Morales; Sean Ekins; Stephen H Wright
Journal:  Mol Pharmacol       Date:  2016-07-14       Impact factor: 4.436

2.  Inhibitory Effects of Triptolide on Human Liver Cytochrome P450 Enzymes and P-Glycoprotein.

Authors:  Hanhua Zhang; Guangkui Ya; Hongbing Rui
Journal:  Eur J Drug Metab Pharmacokinet       Date:  2017-02       Impact factor: 2.441

Review 3.  The Next Era: Deep Learning in Pharmaceutical Research.

Authors:  Sean Ekins
Journal:  Pharm Res       Date:  2016-09-06       Impact factor: 4.200

4.  Data Mining and Computational Modeling of High-Throughput Screening Datasets.

Authors:  Sean Ekins; Alex M Clark; Krishna Dole; Kellan Gregory; Andrew M Mcnutt; Anna Coulon Spektor; Charlie Weatherall; Nadia K Litterman; Barry A Bunin
Journal:  Methods Mol Biol       Date:  2018

Review 5.  Molecular and cellular physiology of organic cation transporter 2.

Authors:  Stephen H Wright
Journal:  Am J Physiol Renal Physiol       Date:  2019-11-04

6.  Multiple Computational Approaches for Predicting Drug Interactions with Human Equilibrative Nucleoside Transporter 1.

Authors:  Siennah R Miller; Thomas R Lane; Kimberley M Zorn; Sean Ekins; Stephen H Wright; Nathan J Cherrington
Journal:  Drug Metab Dispos       Date:  2021-05-12       Impact factor: 3.579

7.  Machine Learning Model Analysis and Data Visualization with Small Molecules Tested in a Mouse Model of Mycobacterium tuberculosis Infection (2014-2015).

Authors:  Sean Ekins; Alexander L Perryman; Alex M Clark; Robert C Reynolds; Joel S Freundlich
Journal:  J Chem Inf Model       Date:  2016-07-01       Impact factor: 4.956

8.  Capturing the applicability of in vitro-in silico membrane transporter data in chemical risk assessment and biomedical research.

Authors:  Laure-Alix Clerbaux; Sandra Coecke; Annie Lumen; Tomas Kliment; Andrew P Worth; Alicia Paini
Journal:  Sci Total Environ       Date:  2018-07-14       Impact factor: 7.963

  8 in total

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