S Ekins

Summary

Publications

  1. ncbi request reprint Quantitative structure activity relationships for the glucuronidation of simple phenols by expressed human UGT1A6 and UGT1A9
    Brian T Ethell
    Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, Dundee, United Kingdom
    Drug Metab Dispos 30:734-8. 2002
  2. ncbi request reprint In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitors
    Sean Ekins
    GeneGo, Inc, St Joseph, Michigan 49085, USA
    Pharm Res 22:512-7. 2005
  3. ncbi request reprint Computational prediction of human drug metabolism
    Sean Ekins
    GeneGo, Inc, 500 Renaissance Drive, Suite 106, St Joseph, MI 49085, USA
    Expert Opin Drug Metab Toxicol 1:303-24. 2005
  4. doi request reprint Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells
    Hongyu Zhou
    Department of Chemical Biology and Therapeutics, St Jude Research Hospital, Memphis, Tennessee 38105, USA
    J Med Chem 51:1242-51. 2008
  5. pmc Computational databases, pathway and cheminformatics tools for tuberculosis drug discovery
    Sean Ekins
    Collaborations in Chemistry, 601 Runnymede Avenue, Jenkintown, PA 19046, USA
    Trends Microbiol 19:65-74. 2011
  6. pmc Evaluation of computational docking to identify pregnane X receptor agonists in the ToxCast database
    Sandhya Kortagere
    Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
    Environ Health Perspect 118:1412-7. 2010
  7. doi request reprint Progress in computational toxicology
    Sean Ekins
    Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay Varina, NC 27526, USA Department of Pharmaceutical Sciences, University of Maryland, 20 Penn Street, Baltimore, MD 21201, USA Department of Pharmacology, Rutgers University Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599 7355, USA Electronic address
    J Pharmacol Toxicol Methods 69:115-40. 2014
  8. ncbi request reprint Bayesian models for screening and TB Mobile for target inference with Mycobacterium tuberculosis
    Sean Ekins
    Collaborative Drug Discovery, 1633 Bayshore Highway, Suite 342, Burlingame, CA 94010, USA Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay Varina, NC 27526, USA Electronic address
    Tuberculosis (Edinb) 94:162-9. 2014
  9. ncbi request reprint Curing TB with open science
    Sean Ekins
    Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay Varina, NC 27526, USA Collaborative Drug Discovery, 1633 Bayshore Highway, Suite 342, Burlingame, CA 94010, USA Electronic address
    Tuberculosis (Edinb) 94:183-5. 2014
  10. doi request reprint Combining computational methods for hit to lead optimization in Mycobacterium tuberculosis drug discovery
    Sean Ekins
    Collaborative Drug Discovery, 1633 Bayshore Highway, Suite 342, Burlingame, California, 94010, USA
    Pharm Res 31:414-35. 2014

Detail Information

Publications95

  1. ncbi request reprint Quantitative structure activity relationships for the glucuronidation of simple phenols by expressed human UGT1A6 and UGT1A9
    Brian 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...
  2. ncbi request reprint In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitors
    Sean Ekins
    GeneGo, Inc, St Joseph, Michigan 49085, USA
    Pharm Res 22:512-7. 2005
    ..We have taken an iterative in vitro and in silico approach to the discovery of molecules with hPEPT1 affinity...
  3. ncbi request reprint Computational prediction of human drug metabolism
    Sean 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...
  4. doi request reprint Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells
    Hongyu 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...
  5. pmc Computational databases, pathway and cheminformatics tools for tuberculosis drug discovery
    Sean Ekins
    Collaborations in Chemistry, 601 Runnymede Avenue, Jenkintown, PA 19046, USA
    Trends Microbiol 19:65-74. 2011
    ..We suggest that these computational approaches should be optimally integrated within a workflow with experimental approaches to accelerate TB drug discovery...
  6. pmc Evaluation of computational docking to identify pregnane X receptor agonists in the ToxCast database
    Sandhya Kortagere
    Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
    Environ Health Perspect 118:1412-7. 2010
    ..The pregnane X receptor (PXR) is a key transcriptional regulator of many genes [e.g., cytochrome P450s (CYP2C9, CYP3A4, CYP2B6), MDR1] involved in xenobiotic metabolism and excretion...
  7. doi request reprint Progress in computational toxicology
    Sean Ekins
    Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay Varina, NC 27526, USA Department of Pharmaceutical Sciences, University of Maryland, 20 Penn Street, Baltimore, MD 21201, USA Department of Pharmacology, Rutgers University Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599 7355, USA Electronic address
    J Pharmacol Toxicol Methods 69:115-40. 2014
    ..Computational methods have been widely applied to toxicology across pharmaceutical, consumer product and environmental fields over the past decade. Progress in computational toxicology is now reviewed...
  8. ncbi request reprint Bayesian models for screening and TB Mobile for target inference with Mycobacterium tuberculosis
    Sean Ekins
    Collaborative Drug Discovery, 1633 Bayshore Highway, Suite 342, Burlingame, CA 94010, USA Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay Varina, NC 27526, USA Electronic address
    Tuberculosis (Edinb) 94:162-9. 2014
    ..tuberculosis target annotations. These predictions may serve as a mechanism for prioritizing compounds for further optimization. ..
  9. ncbi request reprint Curing TB with open science
    Sean Ekins
    Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay Varina, NC 27526, USA Collaborative Drug Discovery, 1633 Bayshore Highway, Suite 342, Burlingame, CA 94010, USA Electronic address
    Tuberculosis (Edinb) 94:183-5. 2014
    ..There is little if any global coordination or collaboration and subsequently there are likely to be huge data silos and duplication of efforts. We now propose steps to remedy this by fostering more open science in TB research. ..
  10. doi request reprint Combining computational methods for hit to lead optimization in Mycobacterium tuberculosis drug discovery
    Sean Ekins
    Collaborative Drug Discovery, 1633 Bayshore Highway, Suite 342, Burlingame, California, 94010, USA
    Pharm Res 31:414-35. 2014
    ..We have used this data for building computational models as an approach to minimize the number of compounds tested...
  11. pmc A generalizable pre-clinical research approach for orphan disease therapy
    Chandree L Beaulieu
    Children s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada
    Orphanet J Rare Dis 7:39. 2012
    ..In addition to enabling academic pre-clinical research, strategies such as this may also aid in seeding startup companies, as well as further engaging the pharmaceutical industry in the treatment of rare genetic disease...
  12. pmc Dispensing processes impact apparent biological activity as determined by computational and statistical analyses
    Sean Ekins
    Collaborations in Chemistry, Fuquay Varina, North Carolina, USA
    PLoS ONE 8:e62325. 2013
    ..In short, traditional dispensing processes are another important source of error in high-throughput screening that impacts computational and statistical analyses. These findings have far-reaching implications in biological research...
  13. pmc Enhancing hit identification in Mycobacterium tuberculosis drug discovery using validated dual-event Bayesian models
    Sean Ekins
    Collaborative Drug Discovery, Burlingame, California, United States of America
    PLoS ONE 8:e63240. 2013
    ..The computational models developed herein and the commercially available molecules derived from them are now available to any group pursuing Mtb drug discovery...
  14. pmc TB Mobile: a mobile app for anti-tuberculosis molecules with known targets
    Sean Ekins
    Collaborative Drug Discovery, 1633 Bayshore Highway, Suite 342, Burlingame, CA 94010, USA
    J Cheminform 5:13. 2013
    ..An increasing number of researchers are focused on strategies for developing inhibitors of Mycobacterium tuberculosis (Mtb) as tuberculosis (TB) drugs...
  15. pmc Bayesian models leveraging bioactivity and cytotoxicity information for drug discovery
    Sean Ekins
    Collaborative Drug Discovery, 1633 Bayshore Highway, Suite 342, Burlingame, CA 94010, USA
    Chem Biol 20:370-8. 2013
    ..The most potent hit exhibits the in vitro activity and in vitro/in vivo safety profile of a drug lead. These Bayesian models offer significant economies in time and cost to drug discovery...
  16. doi request reprint Four disruptive strategies for removing drug discovery bottlenecks
    Sean Ekins
    Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay Varina, NC 27526, USA
    Drug Discov Today 18:265-71. 2013
    ..We describe four strategies to rectify the current unsustainable situation...
  17. doi request reprint Bottlenecks caused by software gaps in miRNA and RNAi research
    Sean Ekins
    Collaborative Drug Discovery, 1633 Bayshore Highway, Suite 342, Burlingame, California 94010, USA
    Pharm Res 29:1717-21. 2012
    ..For example a new software application could be created that provides interactive, comprehensive target analysis that leverages past datasets to lead to statistically stronger analyses...
  18. pmc A substrate pharmacophore for the human organic cation/carnitine transporter identifies compounds associated with rhabdomyolysis
    Sean Ekins
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, 20 Penn Street, Baltimore, Maryland 21201, USA
    Mol Pharm 9:905-13. 2012
    ....
  19. pmc Using molecular similarity to highlight the challenges of routine immunoassay-based drug of abuse/toxicology screening in emergency medicine
    Matthew D Krasowski
    Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
    BMC Emerg Med 9:5. 2009
    ..For immunoassays targeted at a particular class of drugs, there can also be false negatives if there is failure to detect some drugs or their metabolites within that class...
  20. pmc The evolution of farnesoid X, vitamin D, and pregnane X receptors: insights from the green-spotted pufferfish (Tetraodon nigriviridis) and other non-mammalian species
    Matthew D Krasowski
    Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA
    BMC Biochem 12:5. 2011
    ..We utilize homology modelling, docking, and pharmacophore studies to understand the structural features of the Tetraodon receptors...
  21. ncbi request reprint Application of data mining approaches to drug delivery
    Sean 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...
  22. doi request reprint In silico repositioning of approved drugs for rare and neglected diseases
    Sean Ekins
    Collaborations in Chemistry, 601 Runnymede Avenue, Jenkintown, PA 19046, USA
    Drug Discov Today 16:298-310. 2011
    ....
  23. doi request reprint Computational discovery of novel low micromolar human pregnane X receptor antagonists
    Sean 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...
  24. doi request reprint Finding promiscuous old drugs for new uses
    Sean Ekins
    Collaborations in Chemistry, 601 Runnymede Avenue, Jenkintown, Pennsylvania 19046, USA
    Pharm Res 28:1785-91. 2011
    ..We have created databases which can be searched by the public and envisage that these can be updated as more studies are published...
  25. ncbi request reprint Insights for human ether-a-go-go-related gene potassium channel inhibition using recursive partitioning and Kohonen and Sammon mapping techniques
    Sean 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...
  26. ncbi request reprint Future directions for drug transporter modelling
    S Ekins
    Collaborations in Chemistry, Jenkintown, PA, USA
    Xenobiotica 37:1152-70. 2007
    ..The implications of early assessment of transporter activity, current advances in QSAR, and other computational methods for future development of these and systems-based approaches will be discussed...
  27. ncbi request reprint 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...
  28. doi request reprint When pharmaceutical companies publish large datasets: an abundance of riches or fool's gold?
    Sean Ekins
    Collaborations in Chemistry, Jenkintown, PA 19046, USA
    Drug Discov Today 15:812-5. 2010
    ..We also suggest approaches that could enhance the value of such datasets to the community and theoretically offer an immediate benefit to the search for leads for other neglected diseases...
  29. doi request reprint Chemical space: missing pieces in cheminformatics
    Sean Ekins
    Collaborations in Chemistry, 601 Runnymede Avenue, Jenkintown, Pennsylvania 19046, USA
    Pharm Res 27:2035-9. 2010
    ..We describe the needs and opportunities which may benefit from the development of open cheminformatics technologies, mobile computing, the movement of software to the cloud and precompetitive initiatives...
  30. doi request reprint A predictive ligand-based Bayesian model for human drug-induced liver injury
    Sean Ekins
    Collaborations in Chemistry, 601 Runnymede Ave, Jenkintown, PA 19046, USA
    Drug Metab Dispos 38:2302-8. 2010
    ..These computational models may represent cost-effective selection criteria before in vitro or in vivo experimental studies...
  31. pmc Human pregnane X receptor antagonists and agonists define molecular requirements for different binding sites
    Sean 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...
  32. pmc In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling
    S Ekins
    ACT LLC, 1 Penn Plaza, New York, NY 10119, USA
    Br J Pharmacol 152:9-20. 2007
    ..Further applications of these methods to specific targets and their limitations will be discussed in the second accompanying part of this review...
  33. doi request reprint Evolving molecules using multi-objective optimization: applying to ADME/Tox
    Sean Ekins
    Collaborations in Chemistry, 601 Runnymede Avenue, Jenkintown, PA 19046, USA
    Drug Discov Today 15:451-60. 2010
    ..We provide several examples of how Pareto optimization implemented in Pareto Ligand Designer can be used to make trade-offs between these different predicted or real molecular properties to result in better predicted compounds...
  34. doi request reprint Precompetitive preclinical ADME/Tox data: set it free on the web to facilitate computational model building and assist drug development
    Sean Ekins
    Collaborations in Chemistry, Jenkintown, PA 19046, USA
    Lab Chip 10:13-22. 2010
    ....
  35. pmc Molecular characterization of CYP2B6 substrates
    Sean 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...
  36. ncbi request reprint Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors
    Sean 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...
  37. pmc In silico pharmacology for drug discovery: applications to targets and beyond
    S Ekins
    ACT LLC, 1 Penn Plaza, New York, NY 10119, USA
    Br J Pharmacol 152:21-37. 2007
    ....
  38. pmc Evolution of pharmacologic specificity in the pregnane X receptor
    Sean Ekins
    Collaborations in Chemistry, Inc, Jenkintown, PA, USA
    BMC Evol Biol 8:103. 2008
    ....
  39. ncbi request reprint Towards a new age of virtual ADME/TOX and multidimensional drug discovery
    Sean Ekins
    Concurrent Pharmaceuticals Inc, 502 West Office Center Drive, Fort Washington, PA 19034, USA
    Mol Divers 5:255-75. 2002
    ....
  40. pmc Challenges predicting ligand-receptor interactions of promiscuous proteins: the nuclear receptor PXR
    Sean Ekins
    Collaborations in Chemistry, Jenkintown, Pennsylvania, United States of America
    PLoS Comput Biol 5:e1000594. 2009
    ..This study emphasizes this aspect, illustrating modest success using the largest quantitative data set to date and multiple modeling approaches...
  41. ncbi request reprint Three-dimensional quantitative structure-activity relationship for inhibition of human ether-a-go-go-related gene potassium channel
    Sean Ekins
    Lilly Research Laboratories, Eli Lilly and Co, Indianapolis, IN, USA
    J Pharmacol Exp Ther 301:427-34. 2002
    ....
  42. ncbi request reprint Predicting undesirable drug interactions with promiscuous proteins in silico
    Sean Ekins
    Concurrent Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA
    Drug Discov Today 9:276-85. 2004
    ....
  43. ncbi request reprint Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein
    Sean Ekins
    Lilly Research Laboratories, Eli Lilly and Co, Lilly Corporate Center, Indianapolis, Indiana, USA
    Mol Pharmacol 61:964-73. 2002
    ..Utilization of such models may prove to be of value for prediction of molecules that may modulate one or more P-gp binding sites...
  44. ncbi request reprint Towards a new age of virtual ADME/TOX and multidimensional drug discovery
    Sean Ekins
    Concurrent Pharmaceuticals Inc, 502 West Office Center Drive, Fort Washington, PA 19034, USA
    J Comput Aided Mol Des 16:381-401. 2002
    ....
  45. ncbi request reprint Three- and four-dimensional-quantitative structure activity relationship (3D/4D-QSAR) analyses of CYP2C9 inhibitors
    S 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...
  46. ncbi request reprint Application of in silico approaches to predicting drug--drug interactions
    S 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...
  47. ncbi request reprint Examination of purported probes of human CYP2B6
    S 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...
  48. ncbi request reprint Progress in predicting human ADME parameters in silico
    S 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...
  49. ncbi request reprint Alterations of the catalytic activities of drug-metabolizing enzymes in cultures of human liver slices
    M 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...
  50. ncbi request reprint In vitro and pharmacophore insights into CYP3A enzymes
    Sean Ekins
    Concurrent Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA
    Trends Pharmacol Sci 24:161-6. 2003
    ....
  51. ncbi request reprint Comprehensive computational assessment of ADME properties using mapping techniques
    Konstantin V Balakin
    Chemical Diversity, Inc, 11558 Sorrento Valley Road, San Diego, CA 92121, USA
    Curr Drug Discov Technol 2:99-113. 2005
    ....
  52. ncbi request reprint Present and future in vitro approaches for drug metabolism
    S 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...
  53. ncbi request reprint In silico ADME/Tox: the state of the art
    Sean Ekins
    Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285 0730, USA
    J Mol Graph Model 20:305-9. 2002
    ....
  54. ncbi request reprint Generation and validation of rapid computational filters for cyp2d6 and cyp3a4
    Sean Ekins
    Concurrent Pharmaceuticals Inc, Fort Washington, PA 19034, USA
    Drug Metab Dispos 31:1077-80. 2003
    ....
  55. ncbi request reprint Pharmacophore and three-dimensional quantitative structure activity relationship methods for modeling cytochrome p450 active sites
    S Ekins
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA
    Drug Metab Dispos 29:936-44. 2001
    ....
  56. ncbi request reprint A pharmacophore for human pregnane X receptor ligands
    Sean 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...
  57. ncbi request reprint Application of three-dimensional quantitative structure-activity relationships of P-glycoprotein inhibitors and substrates
    Sean Ekins
    Lilly Research Laboratories, Eli Lilly and Co, Lilly Corporate Center, Indianapolis, Indiana, USA
    Mol Pharmacol 61:974-81. 2002
    ..These 3D-QSAR models will be useful for future prediction of likely substrates and inhibitors of P-gp...
  58. ncbi request reprint Three-dimensional quantitative structure-permeability relationship analysis for a series of inhibitors of rhinovirus replication
    S 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...
  59. ncbi request reprint Kohonen maps for prediction of binding to human cytochrome P450 3A4
    Konstantin 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...
  60. doi request reprint Chemical target and pathway toxicity mechanisms defined in primary human cell systems
    Ellen L Berg
    BioSeek, Inc, 310 Utah 100, South San Francisco, CA 94080, USA
    J Pharmacol Toxicol Methods 61:3-15. 2010
    ..Approaches that detect and discriminate a broad range of mechanisms in testing formats that are predictive and yet cost-effective are needed...
  61. ncbi request reprint A novel method for visualizing nuclear hormone receptor networks relevant to drug metabolism
    Sean 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...
  62. ncbi request reprint 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...
  63. ncbi request reprint Methods for predicting human drug metabolism
    Larry 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...
  64. ncbi request reprint A ligand-based approach to understanding selectivity of nuclear hormone receptors PXR, CAR, FXR, LXRalpha, and LXRbeta
    Sean 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?..
  65. ncbi request reprint Quantitative structure-metabolism relationship modeling of metabolic N-dealkylation reaction rates
    Konstantin 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...
  66. ncbi request reprint In silico approaches to predicting drug metabolism, toxicology and beyond
    S Ekins
    Concurrent Pharmaceuticals Inc, 502 West Office Center Drive, Fort Washington, PA 19034, USA
    Biochem Soc Trans 31:611-4. 2003
    ..Some relatively simple approaches may have value when it comes to combining data from multiple models in order to improve and focus drug discovery on the molecules most likely to succeed...
  67. ncbi request reprint A combined approach to drug metabolism and toxicity assessment
    Sean 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...
  68. ncbi request reprint Prediction of human drug metabolizing enzyme induction
    Dayna 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...
  69. ncbi request reprint Pathway mapping tools for analysis of high content data
    Sean Ekins
    GeneGo, Jerkintown, PA, USA
    Methods Mol Biol 356:319-50. 2007
    ..We describe in detail the integrated data-mining tools applicable to building biological networks developed by GeneGo, namely, MetaCore and MetaDrug...
  70. doi request reprint Novel web-based tools combining chemistry informatics, biology and social networks for drug discovery
    Moses Hohman
    Collaborative Drug Discovery, Inc, Burlingame, CA 94403, USA
    Drug Discov Today 14:261-70. 2009
    ..We will illustrate several case studies for anti-malarial research enabled by this platform, which we suggest could be easily expanded more broadly for pharmaceutical research in general...
  71. ncbi request reprint Modeling of active transport systems
    Eric Y Zhang
    Division of Pharmaceutics, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210 1291, USA
    Adv Drug Deliv Rev 54:329-54. 2002
    ..Clearly the future growth in knowledge of transporter function will be led by integrated in vitro and in silico approaches...
  72. ncbi request reprint The PXR crystal structure: the end of the beginning
    Sean Ekins
    Trends Pharmacol Sci 23:49-50. 2002
  73. ncbi request reprint Effects of antipsychotic drugs on I(to), I (Na), I (sus), I (K1), and hERG: QT prolongation, structure activity relationship, and network analysis
    William J Crumb
    Department of Pediatrics Cardiology, Tulane University School of Medicine, New Orleans, Lousiana, USA
    Pharm Res 23:1133-43. 2006
    ..To evaluate in vitro and computationally model the effects of selected antipsychotic drugs on several ionic currents that contribute to changes in the action potential in cardiac tissue...
  74. ncbi request reprint Reengineering the pharmaceutical industry by crash-testing molecules
    Peter 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...
  75. ncbi request reprint Systems-ADME/Tox: resources and network approaches
    Sean 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...
  76. ncbi request reprint Comparative pharmacophore modeling of organic anion transporting polypeptides: a meta-analysis of rat Oatp1a1 and human OATP1B1
    Cheng 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...
  77. ncbi request reprint Techniques: application of systems biology to absorption, distribution, metabolism, excretion and toxicity
    Sean 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...
  78. ncbi request reprint PXR and the regulation of apoA1 and HDL-cholesterol in rodents
    Kenneth 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...
  79. ncbi request reprint Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1
    Dallas Bednarczyk
    Department of Physiology, University of Arizona, Tucson, Arizona, USA
    Mol Pharmacol 63:489-98. 2003
    ..These results indicate how a combination of computational and in vitro approaches may yield insight into the binding affinity of transporters and may be applicable to predicting these properties for new therapeutics...
  80. ncbi request reprint 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...
  81. ncbi request reprint Rapid identification of P-glycoprotein substrates and inhibitors
    Cheng Chang
    Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD 21201, USA
    Drug Metab Dispos 34:1976-84. 2006
    ....
  82. pmc Pharmacophore-based discovery of ligands for drug transporters
    Cheng 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
    ....
  83. doi request reprint A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine
    Kazuto 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...
  84. pmc Bacterial peptide recognition and immune activation facilitated by human peptide transporter PEPT2
    Peter 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...
  85. pmc New predictive models for blood-brain barrier permeability of drug-like molecules
    Sandhya 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...
  86. pmc Ligand specificity and evolution of liver X receptors
    Erica 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...
  87. pmc Evolution of the bile salt nuclear receptor FXR in vertebrates
    Erica 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...
  88. ncbi request reprint Improving the drug selection and development process for combination devices
    Maggie 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...
  89. ncbi request reprint Computational models to assign biopharmaceutics drug disposition classification from molecular structure
    Akash 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)...
  90. pmc Machine learning methods and docking for predicting human pregnane X receptor activation
    Akash 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...
  91. ncbi request reprint Pharmacophore modeling of cytochromes P450
    Marcel 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
    ....
  92. ncbi request reprint Structural biology and function of solute transporters: implications for identifying and designing substrates
    Eric 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...
  93. ncbi request reprint Molecular determinants of substrate/inhibitor binding to the human and rabbit renal organic cation transporters hOCT2 and rbOCT2
    Wendy 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...
  94. ncbi request reprint A novel method for generation of signature networks as biomarkers from complex high throughput data
    Yuri Nikolsky
    Computational Biology Genego Inc, 500 Renaissance Drive, Suite 106, St Joseph, MI 49085, USA
    Toxicol Lett 158:20-9. 2005
    ..These signature networks represent an approach to identify biomarkers and a general approach for discovering new relationships in complex high throughput toxicology data...
  95. pmc Intrinsic disorder in nuclear hormone receptors
    Matthew 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...