Research Topics
| S EkinsSummaryAffiliation: Eli Lilly and Company Country: USA Publications
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Detail Information
Publications
Molecular characterization of CYP2B6 substratesSean Ekins
Collaborations in Chemistry, 601 Runnymede Ave, Jenkintown, PA 19046 USA
Curr Drug Metab 9:363-73. 2008..We have shown that CYP2B6 substrates are generally small hydrophobic molecules that are frequently central nervous system active, which may be important for drug discovery research...
Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome p450 active sitesS Ekins
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
Drug Metab Dispos 29:936-44. 2001....- In silico ADME/Tox: the state of the artSean Ekins
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285 0730, USA
J Mol Graph Model 20:305-9. 2002.... - Three-dimensional quantitative structure-permeability relationship analysis for a series of inhibitors of rhinovirus replicationS Ekins
Lilly Research Laboratories, Eli Lilly and Co, Lilly Corporate Center, Indianapolis, IN 46285, USA
J Chem Inf Comput Sci 41:1578-86. 2001..In summary it would appear that the 3D techniques have considerable value in predicting passive permeability for a congeneric series of molecules, representing a valuable asset for drug discovery... - A pharmacophore for human pregnane X receptor ligandsSean Ekins
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 0730, Indianapolis, IN 46285, USA
Drug Metab Dispos 30:96-9. 2002..Ultimately, this will aid in the selection of molecules with a lesser capacity to be potent PXR ligands and thus avoid induction of numerous drug-metabolizing enzymes and MDR1... - Application of in silico approaches to predicting drug--drug interactionsS Ekins
Lilly Research Laboratories, Lilly Corporate Center, Drop Code 1730, Indianapolis, IN 46285, USA
J Pharmacol Toxicol Methods 45:65-9. 2001..The present paper briefly reviews the application of some computational tools applied to predicting DDIs and will provide the reader with an idea of their utility... - Present and future in vitro approaches for drug metabolismS Ekins
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 0730, Indianapolis, IN 46285, USA
J Pharmacol Toxicol Methods 44:313-24. 2000..This review will focus on and assess the nature of present in vitro metabolism approaches and indicate how they are likely to develop in the future... - Progress in predicting human ADME parameters in silicoS Ekins
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 0730, Indianapolis, IN 46285, USA
J Pharmacol Toxicol Methods 44:251-72. 2000..This review will assess how computational approaches for ADME parameters have evolved and how they are likely to progress... - Three-dimensional quantitative structure activity relationship computational approaches for prediction of human in vitro intrinsic clearanceS Ekins
Central Research Division, Pfizer Inc, Groton, Connecticut
J Pharmacol Exp Ther 295:463-73. 2000..These present models represent a preliminary application of QSAR software to modeling and prediction of human in vitro intrinsic clearance... - Three- and four-dimensional-quantitative structure activity relationship (3D/4D-QSAR) analyses of CYP2C9 inhibitorsS Ekins
Department of Drug Disposition, Lilly Research Laboratories, Eli Lilly and Co, Lilly Corporate Center, Indianapolis, Indiana, USA
Drug Metab Dispos 28:994-1002. 2000..These 3D- and 4D-QSAR models of CYP inhibition will aid in future prediction of drug-drug interactions... - Alterations of the catalytic activities of drug-metabolizing enzymes in cultures of human liver slicesM VandenBranden
Department of Drug Disposition, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA
Drug Metab Dispos 26:1063-8. 1998..Therefore, the development of culture methods for human liver slices that can improve the preservation of the drug-metabolizing capabilities may be required... - Examination of purported probes of human CYP2B6S Ekins
Department of Drug Disposition, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA
Pharmacogenetics 7:165-79. 1997..Furthermore, the specificity of both antibody and chemical inhibitor (ORP) probes previously suggested to be specific for CYP2B6 is also questioned... - (R)-, (S)-, and racemic fluoxetine N-demethylation by human cytochrome P450 enzymesJ M Margolis
Drug Metabolism Department, Candidate Synthesis, Enhancement, and Evaluation, Central Research Division, Pfizer Inc, Groton, Connecticut, USA
Drug Metab Dispos 28:1187-91. 2000..Together, these findings suggest a significant role for the polymorphically expressed CYP2D6 in fluoxetine clearance and are consistent with reports on the clinical pharmacokinetics of fluoxetine... - A novel method for visualizing nuclear hormone receptor networks relevant to drug metabolismSean Ekins
Computational Biology, GeneGo, Inc, 500 Renaissance Drive, Suite 106, St Joseph, MI 49085, USA
Drug Metab Dispos 33:474-81. 2005..The database represents a novel knowledge mining and analytical tool that, to be relevant, requires continual updating to evolve alongside other key storage systems and sources of biological knowledge... - In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitorsSean Ekins
GeneGo, Inc, St Joseph, Michigan 49085, USA
Pharm Res 22:512-7. 2005.... - Human pregnane X receptor antagonists and agonists define molecular requirements for different binding sitesSean Ekins
ACT LLC, 601 Runnymede Avenue, Jenkintown, PA 19046, USA
Mol Pharmacol 72:592-603. 2007..These observations bear significant implications for future discovery of molecules that are more selective and potent antagonists... - Prediction of human drug metabolizing enzyme inductionDayna C Mankowski
Rib-X Pharmaceuticals, Inc, New Haven, CT 06511, USA
Curr Drug Metab 4:381-91. 2003..This review will cover the various in vitro and in silico methods developed for prediction of key inducers of CYPs and other proteins, as well as the limitations of such technologies and applications in the future... - Computational approaches that predict metabolic intermediate complex formation with CYP3A4 (+b5)David R Jones
Indiana University School of Medicine, Department of Medicine, Division of Clinical Pharmacology, Wishard Memorial Hospital, Myers Bldg W7123, Indianapolis, IN 46220, USA
Drug Metab Dispos 35:1466-75. 2007..The preliminary pharmacophores provide structural insights that complement those for CYP3A4 inhibitors and substrates... - In vitro and pharmacophore insights into CYP3A enzymesSean Ekins
Concurrent Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA
Trends Pharmacol Sci 24:161-6. 2003.... - A ligand-based approach to understanding selectivity of nuclear hormone receptors PXR, CAR, FXR, LXRalpha, and LXRbetaSean Ekins
Concurrent Pharmaceuticals Inc, Fort Washington, Pennsylvania 19034, USA
Pharm Res 19:1788-800. 2002..Simultaneously, we might learn which came first: the transporter, the enzyme, or the nuclear hormone receptor?.. - Comprehensive computational assessment of ADME properties using mapping techniquesKonstantin V Balakin
Chemical Diversity, Inc, 11558 Sorrento Valley Road, San Diego, CA 92121, USA
Curr Drug Discov Technol 2:99-113. 2005.... 
Computational discovery of novel low micromolar human pregnane X receptor antagonistsSean Ekins
Collaborations in Chemistry, Jenkintown, PA 19046, USA
Mol Pharmacol 74:662-72. 2008..8 microM), that seems to be a PXR antagonist in vitro. These observations are important for predicting whether further molecules may interact with PXR as antagonists in vivo with potential therapeutic applications...- The PXR crystal structure: the end of the beginningSean Ekins
Trends Pharmacol Sci 23:49-50. 2002 - Methods for predicting human drug metabolismLarry J Jolivette
Preclinical Drug Discovery, Cardiovascular and Urogenital Centre of Excellence in Drug Discovery, GlaxoSmithKline, King of Prussia, Pennsylvania, USA
Adv Clin Chem 43:131-76. 2007..The utilization of these methods for pharmaceutical and other applications as well as their integration is discussed as it is likely that hybrid methods will provide the most success... - Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitorsSean Ekins
Computational Biology, ACT LLC, 601 Runnymede Ave, Jenkintown, PA 19046, USA
Drug Metab Dispos 35:493-500. 2007..This study has demonstrated the potential for ligand-based computational pharmacophore modeling of human CYP51 and enables a high-throughput screening system for drug discovery and data base mining... - Classification of metabolites with kernel-partial least squares (K-PLS)Mark J Embrechts
ACT LLC, 601 Runnymede Ave, Jenkintown, PA 19046, USA
Drug Metab Dispos 35:325-7. 2007..Improvements can be achieved using considerably larger datasets that contain more positive examples for the less frequently occurring metabolite rules, as well as the external evaluation of novel molecules... - Computational models to assign biopharmaceutics drug disposition classification from molecular structureAkash Khandelwal
Department of Pharmaceutical Sciences, University of Maryland, 20 Penn Street, Baltimore, Maryland 21201, USA
Pharm Res 24:2249-62. 2007..We applied in silico methods to automatically classify drugs according to the Biopharmaceutics Drug Disposition Classification System (BDDCS)... - Improving the drug selection and development process for combination devicesMaggie A Z Hupcey
PA Consulting Group, 600 College Road East, Suite 1120, Princeton, NJ 08540, USA
Drug Discov Today 12:844-52. 2007..This review addresses the many dimensions including opportunities and challenges of combination device development from both the device and pharmaceutical perspectives... - Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cellsHongyu Zhou
Department of Chemical Biology and Therapeutics, St Jude Research Hospital, Memphis, Tennessee 38105, USA
J Med Chem 51:1242-51. 2008..Activities against P-gp-overexpressing and paclitaxel-resistant cell line H460 taxR and modeling using a previously validated P-gp substrate pharmacophore suggested that active compounds were not likely P-gp substrates... - Intrinsic disorder in nuclear hormone receptorsMatthew D Krasowski
Department of Pathology, University of Pittsburgh, Scaife Hall S 737, 3550 Terrace Street Pittsburgh, Pennsylvania 15261, USA
J Proteome Res 7:4359-72. 2008..This information enables further understanding of these therapeutic targets... - Machine learning methods and docking for predicting human pregnane X receptor activationAkash Khandelwal
Department of Pharmaceutical Sciences, University of Maryland, 20 Penn Street, Baltimore, Maryland 21201, USA
Chem Res Toxicol 21:1457-67. 2008..These methods could be used for high throughput virtual screening to assess for PXR activation, prior to in vitro testing to predict potential drug-drug interactions... - A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestineKazuto Yasuda
Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, Tennessee, USA
Drug Metab Dispos 36:1689-97. 2008..In summary, nafcillin, dicloxacillin, cephradine, tetracycline, sulfixoxazole, erythromycin, clindamycin, and griseofulvin exhibit a clear propensity to induce CYP3A4 and warrant further clinical investigation... - Bacterial peptide recognition and immune activation facilitated by human peptide transporter PEPT2Peter W Swaan
Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, USA
Am J Respir Cell Mol Biol 39:536-42. 2008..Based on these findings we report that PEPT2 plays a vital role in microbial recognition by NLR proteins, particularly with regard to airborne pathogens, thereby participating in host defense in the lung... - New predictive models for blood-brain barrier permeability of drug-like moleculesSandhya Kortagere
Department of Pharmacology and Environmental Bioinformatics and Computational Toxicology Center ebCTC, University of Medicine and Dentistry of New Jersey UMDNJ Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey, 08854, USA
Pharm Res 25:1836-45. 2008..The goals of the present study were to apply a generalized regression model and support vector machine (SVM) models with Shape Signatures descriptors, to the domain of blood-brain barrier (BBB) modeling... - Ligand specificity and evolution of liver X receptorsErica J Reschly
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, United States
J Steroid Biochem Mol Biol 110:83-94. 2008..The results suggest that LXRs have a long evolutionary history, with vertebrate LXRs diverging from invertebrate LXRs in ligand specificity... - Evolution of pharmacologic specificity in the pregnane X receptorSean Ekins
Collaborations in Chemistry, Inc, Jenkintown, PA, USA
BMC Evol Biol 8:103. 2008.... - Evolution of the bile salt nuclear receptor FXR in vertebratesErica J Reschly
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA
J Lipid Res 49:1577-87. 2008..Our observations present an integrated picture of the coevolution of bile salt structure and of the binding pocket of their target nuclear receptor FXR... - Pharmacophore-based discovery of ligands for drug transportersCheng Chang
Department of Pharmaceutical Sciences, School of Pharmacy, 20 Penn Street, HSF2-621, University of Maryland, Baltimore, Baltimore, MD 21201, USA
Adv Drug Deliv Rev 58:1431-50. 2006.... - Application of data mining approaches to drug deliverySean Ekins
ACT LLC, 1 Penn Plaza 36th floor, New York, NY 10119, USA
Adv Drug Deliv Rev 58:1409-30. 2006..We will discuss some areas of unmet needs in the area of data mining for drug delivery that can be addressed with new software tools or databases of relevance to future pharmaceutical projects... - Rapid identification of P-glycoprotein substrates and inhibitorsCheng Chang
Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD 21201, USA
Drug Metab Dispos 34:1976-84. 2006.... - Quantitative structure activity relationships for the glucuronidation of simple phenols by expressed human UGT1A6 and UGT1A9Brian T Ethell
Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, Dundee, United Kingdom
Drug Metab Dispos 30:734-8. 2002..The K(m) values for UGT1A9 showed a similar relationship to UGT1A6 but with much lower K(m) values and greater variability in range of this value... - Optimizing higher throughput methods to assess drug-drug interactions for CYP1A2, CYP2C9, CYP2C19, CYP2D6, rCYP2D6, and CYP3A4 in vitro using a single point IC(50)Feng Gao
Pfizer Global Research and Development, Groton, CT, USA
J Biomol Screen 7:373-82. 2002..In addition, the algorithmic approach we propose would obviously be applicable for other in vitro bioactivity and therapeutic target enzyme and receptor screens... - Structural biology and function of solute transporters: implications for identifying and designing substratesEric Y Zhang
Division of Pharmaceutics, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210-1291, USA
Drug Metab Rev 34:709-50. 2002..Clearly the future growth in knowledge of SLC function will be led by integrated in vitro and in silico approaches... - Towards a new age of virtual ADME/TOX and multidimensional drug discoverySean Ekins
Concurrent Pharmaceuticals Inc, 502 West Office Center Drive, Fort Washington, PA 19034, USA
J Comput Aided Mol Des 16:381-401. 2002.... - Towards a new age of virtual ADME/TOX and multidimensional drug discoverySean Ekins
Concurrent Pharmaceuticals Inc, 502 West Office Center Drive, Fort Washington, PA 19034, USA
Mol Divers 5:255-75. 2002.... - Generation and validation of rapid computational filters for cyp2d6 and cyp3a4Sean Ekins
Concurrent Pharmaceuticals Inc, Fort Washington, PA 19034, USA
Drug Metab Dispos 31:1077-80. 2003.... - PXR and the regulation of apoA1 and HDL-cholesterol in rodentsKenneth Bachmann
Department of Pharmacology, University of Toledo, 2801 W Bancroft St, Toledo, OH 43606, USA
Pharmacol Res 50:237-46. 2004..These imidazoles have been shown to increase apoA1 and HDL-C in rats and mice. Taken together, these data suggest that PXR plays an important role in the regulation of apoA1 and HDL-C in rodents... - Kohonen maps for prediction of binding to human cytochrome P450 3A4Konstantin V Balakin
Chemical Diversity Labs, Inc, San Diego, CA, USA
Drug Metab Dispos 32:1183-9. 2004..This computational approach represents a novel method for use in the generation of metabolism models, enabling the scoring of libraries of compounds for their Km values to numerous P450s... - Quantitative structure-metabolism relationship modeling of metabolic N-dealkylation reaction ratesKonstantin V Balakin
Chemical Diversity Labs, Inc, San Diego, CA, USA
Drug Metab Dispos 32:1111-20. 2004..These models represent an initial approach to predicting the rate of P450-mediated metabolism and may be applied and integrated with other models for P450 binding to produce a systems-based approach for predicting drug metabolism... - Molecular determinants of substrate/inhibitor binding to the human and rabbit renal organic cation transporters hOCT2 and rbOCT2Wendy M Suhre
Department of Physiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA
Mol Pharmacol 67:1067-77. 2005..The current models enabled prediction of OCT2 affinity and may prove useful in the prediction of unwanted drug interactions at the level of the renal secretory process... - Techniques: application of systems biology to absorption, distribution, metabolism, excretion and toxicitySean Ekins
GeneGo, 500 Renaissance Drive, Suite 106, St Joseph, MI 49085, USA
Trends Pharmacol Sci 26:202-9. 2005..In this review, we focus on the most recent advances and applications in this area... - Comparative pharmacophore modeling of organic anion transporting polypeptides: a meta-analysis of rat Oatp1a1 and human OATP1B1Cheng Chang
Biophysics Program, The Ohio State University, Columbus, OH, USA
J Pharmacol Exp Ther 314:533-41. 2005..This approach can be extended to other transporters for which limited data are available... - Systems-ADME/Tox: resources and network approachesSean Ekins
GeneGo, 500 Renaissance Drive, Suite 106, St Joseph, MI 49085, USA
J Pharmacol Toxicol Methods 53:38-66. 2006..Examples of networks derived with important drug transporters and drug metabolizing enzymes are provided to demonstrate the network technologies... - Reengineering the pharmaceutical industry by crash-testing moleculesPeter W Swaan
Department of Pharmaceutical Sciences, University of Maryland, 20 Penn Street, Baltimore, MD 21201, USA
Drug Discov Today 10:1191-200. 2005..The successful application of these virtual crash-testing principles by any of its current proponents could revitalize the pharmaceutical industry so that failure is avoided... - A combined approach to drug metabolism and toxicity assessmentSean Ekins
Computational Biology, GeneGo, Inc, 500 Renaissance Drive, Suite 106, St Joseph, MI 49085, USA
Drug Metab Dispos 34:495-503. 2006..These case studies demonstrate the combination of QSARs and systems biology methods... - Insights for human ether-a-go-go-related gene potassium channel inhibition using recursive partitioning and Kohonen and Sammon mapping techniquesSean Ekins
ACT LLC, 601 Runnymede Avenue, Jenkintown, Pennsylvania 19046, USA
J Med Chem 49:5059-71. 2006..This study illustrates that patch clamping data from various literature sources can be combined to generate valid models of hERG inhibition for prospective predictions... - Computational prediction of human drug metabolismSean Ekins
GeneGo, Inc, 500 Renaissance Drive, Suite 106, St Joseph, MI 49085, USA
Expert Opin Drug Metab Toxicol 1:303-24. 2005..This will ultimately aid in hypothesis generation and the early triaging of molecules likely to have undesirable predicted properties or measured effects on key proteins and cellular functions... - Pharmacophore modeling of cytochromes P450Marcel J de Groot
Department of Molecular Informatics, Structure and Design, Pfizer Global Research and Development, Sandwich Laboratories, Kent CT13 9NJ, Sandwich, UK
Adv Drug Deliv Rev 54:367-83. 2002....