drug design

Summary

Summary: The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.

Top Publications

  1. ncbi Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy
    Richard A Friesner
    Department of Chemistry, Columbia University, New York, New York 10036, USA
    J Med Chem 47:1739-49. 2004
  2. ncbi A novel integrated framework and improved methodology of computer-aided drug design
    Calvin Yu chian Chen
    College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China
    Curr Top Med Chem 13:965-88. 2013
  3. ncbi Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening
    Thomas A Halgren
    Schrodinger, L L C, 120 W 45th Street, New York, New York 10036, USA
    J Med Chem 47:1750-9. 2004
  4. ncbi Network pharmacology: the next paradigm in drug discovery
    Andrew L Hopkins
    Division of Biological Chemistry and Drug Discovery, College of Life Science, University of Dundee, Dundee, UK
    Nat Chem Biol 4:682-90. 2008
  5. ncbi Targeting cancer with small molecule kinase inhibitors
    Jianming Zhang
    Dana Farber Cancer Institute, Department of Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 9:28-39. 2009
  6. ncbi Natural products in drug discovery
    Alan L Harvey
    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, UK
    Drug Discov Today 13:894-901. 2008
  7. ncbi Drug repositioning: identifying and developing new uses for existing drugs
    Ted T Ashburn
    Dynogen Pharmaceuticals, Inc, 31 St James Avenue, Suite 905, Boston, Massachusetts 02116, USA
    Nat Rev Drug Discov 3:673-83. 2004
  8. ncbi Improved protein-ligand docking using GOLD
    Marcel L Verdonk
    Astex Technology, Ltd, Cambridge, United Kingdom
    Proteins 52:609-23. 2003
  9. ncbi Can the pharmaceutical industry reduce attrition rates?
    Ismail Kola
    Basic Research at Merck Research Labs, 126 East Lincoln Avenue, Rahway, New Jersey 07075, USA
    Nat Rev Drug Discov 3:711-5. 2004
  10. pmc DrugBank: a knowledgebase for drugs, drug actions and drug targets
    David S Wishart
    Department of Computing Science, University of Alberta, Edmonton, AB, Canada T6G 2E8
    Nucleic Acids Res 36:D901-6. 2008

Detail Information

Publications337 found, 100 shown here

  1. ncbi Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy
    Richard A Friesner
    Department of Chemistry, Columbia University, New York, New York 10036, USA
    J Med Chem 47:1739-49. 2004
    ..Glide is also found to be more accurate than the recently described Surflex method...
  2. ncbi A novel integrated framework and improved methodology of computer-aided drug design
    Calvin Yu chian Chen
    College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China
    Curr Top Med Chem 13:965-88. 2013
    Computer-aided drug design (CADD) is a critical initiating step of drug development, but a single model capable of covering all designing aspects remains to be elucidated...
  3. ncbi Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening
    Thomas A Halgren
    Schrodinger, L L C, 120 W 45th Street, New York, New York 10036, USA
    J Med Chem 47:1750-9. 2004
    ..Comparisons to results for the thymidine kinase and estrogen receptors published by Rognan and co-workers (J. Med. Chem. 2000, 43, 4759-4767) show that Glide 2.5 performs better than GOLD 1.1, FlexX 1.8, or DOCK 4.01...
  4. ncbi Network pharmacology: the next paradigm in drug discovery
    Andrew L Hopkins
    Division of Biological Chemistry and Drug Discovery, College of Life Science, University of Dundee, Dundee, UK
    Nat Chem Biol 4:682-90. 2008
    ..Advances in these areas are creating the foundation of the next paradigm in drug discovery: network pharmacology...
  5. ncbi Targeting cancer with small molecule kinase inhibitors
    Jianming Zhang
    Dana Farber Cancer Institute, Department of Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 9:28-39. 2009
    ..This Review provides a broad overview of some of the approaches currently used to discover and characterize new kinase inhibitors...
  6. ncbi Natural products in drug discovery
    Alan L Harvey
    Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, UK
    Drug Discov Today 13:894-901. 2008
    ..It is hoped that the more efficient and effective application of natural products will improve the drug discovery process...
  7. ncbi Drug repositioning: identifying and developing new uses for existing drugs
    Ted T Ashburn
    Dynogen Pharmaceuticals, Inc, 31 St James Avenue, Suite 905, Boston, Massachusetts 02116, USA
    Nat Rev Drug Discov 3:673-83. 2004
  8. ncbi Improved protein-ligand docking using GOLD
    Marcel L Verdonk
    Astex Technology, Ltd, Cambridge, United Kingdom
    Proteins 52:609-23. 2003
    ..Even at docking speeds of around 1-2 min/compound, the Goldscore function predicts binding energies with a standard deviation of approximately 10.5 kJ/mol...
  9. ncbi Can the pharmaceutical industry reduce attrition rates?
    Ismail Kola
    Basic Research at Merck Research Labs, 126 East Lincoln Avenue, Rahway, New Jersey 07075, USA
    Nat Rev Drug Discov 3:711-5. 2004
  10. pmc DrugBank: a knowledgebase for drugs, drug actions and drug targets
    David S Wishart
    Department of Computing Science, University of Alberta, Edmonton, AB, Canada T6G 2E8
    Nucleic Acids Res 36:D901-6. 2008
    ..Since its first release in 2006, DrugBank has been widely used to facilitate in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical ..
  11. ncbi Extended-connectivity fingerprints
    David Rogers
    J Chem Inf Model 50:742-54. 2010
    ..While the use of ECFPs has been widely adopted and validated, a description of their implementation has not previously been presented in the literature...
  12. ncbi Ligand efficiency: a useful metric for lead selection
    Andrew L Hopkins
    Drug Discov Today 9:430-1. 2004
  13. ncbi Drugs for bad bugs: confronting the challenges of antibacterial discovery
    David J Payne
    Infectious Diseases Centre of Excellence for Drug Discovery, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA
    Nat Rev Drug Discov 6:29-40. 2007
    ....
  14. ncbi Relating protein pharmacology by ligand chemistry
    Michael J Keiser
    Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th St, San Francisco California 94143 2550, USA
    Nat Biotechnol 25:197-206. 2007
    ..These predictions were subsequently confirmed experimentally. Relating receptors by ligand chemistry organizes biology to reveal unexpected relationships that may be assayed using the ligands themselves...
  15. ncbi iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan
    Tsung Ying Tsai
    Laboratory of Computational and Systems Biology, School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan
    J Comput Aided Mol Des 25:525-31. 2011
    ..iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file ..
  16. ncbi LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters
    Gerhard Wolber
    Inte Ligand GmbH, Mariahilferstrasse 74B 11, A 1070 Vienna, Austria
    J Chem Inf Model 45:160-9. 2005
    ..The algorithms for ligand extraction and interpretation as well as the pharmacophore creation technique from the automatically interpreted data are presented and applied to a rhinovirus capsid complex as application example...
  17. pmc Benchmarking sets for molecular docking
    Niu Huang
    Department of Pharmaceutical Chemistry, University of California San Francisco, QB3 Building, 1700 4th Street, Box 2550, San Francisco, California 94143 2550, USA
    J Med Chem 49:6789-801. 2006
    ..DUD is freely available online as a benchmarking set for docking at http://blaster.docking.org/dud/...
  18. pmc APD2: the updated antimicrobial peptide database and its application in peptide design
    Guangshun Wang
    Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198 6805, USA
    Nucleic Acids Res 37:D933-7. 2009
    ..Using frequently occurring residues, we demonstrate database-aided peptide design in different ways. Among the three peptides designed, GLK-19 showed a higher activity against Escherichia coli than human LL-37...
  19. pmc ZINC--a free database of commercially available compounds for virtual screening
    John J Irwin
    Department of Pharmaceutical Chemistry, University of California San Francisco, Genentech Hall, 600 16th Street, San Francisco, California 94143, USA
    J Chem Inf Model 45:177-82. 2005
    ..Users can process their own molecules by uploading them to a server. Our hope is that this database will bring virtual screening libraries to a wide community of structural biologists and medicinal chemists...
  20. ncbi The efficiency of multi-target drugs: the network approach might help drug design
    Peter Csermely
    Department of Medical Chemistry, Semmelweis University, PO Box 260, H 1444 Budapest 8, Hungary
    Trends Pharmacol Sci 26:178-82. 2005
    Despite considerable progress in genome- and proteome-based high-throughput screening methods and rational drug design, the number of successful single-target drugs did not increase appreciably during the past decade...
  21. ncbi The evolving role of natural products in drug discovery
    Frank E Koehn
    Wyeth Research, 401 North Middletown Road, Pearl River, New York 10965, USA
    Nat Rev Drug Discov 4:206-20. 2005
    ....
  22. ncbi Potential mechanisms of atypical antipsychotic-induced metabolic derangement: clues for understanding obesity and novel drug design
    Roberto Coccurello
    Institute of Neuroscience, National Research Council C N R, Via del Fosso di Fiorano, 64 00143 Roma, Italy
    Pharmacol Ther 127:210-51. 2010
    ..For this reason, recently identified obesogenic and diabetogenic mechanisms are the background on which the present work is built and some novel forthcoming lines of investigation suggested...
  23. ncbi A 'rule of three' for fragment-based lead discovery?
    Miles Congreve
    Astex Technology Ltd, 436 Cambridge Science Park, Milton Road, CB4 0QA, Cambridge, UK
    Drug Discov Today 8:876-7. 2003
  24. ncbi A critical assessment of docking programs and scoring functions
    Gregory L Warren
    GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA
    J Med Chem 49:5912-31. 2006
    ..For prediction of compound affinity, none of the docking programs or scoring functions made a useful prediction of ligand binding affinity...
  25. pmc SuperTarget and Matador: resources for exploring drug-target relationships
    Stefan Günther
    Structural Bioinformatics Group, Institute of Molecular Biology and Bioinformatics, Charite University Medicine Berlin, Arnimallee 22, 14195 Berlin, Germany
    Nucleic Acids Res 36:D919-22. 2008
    ..SuperTarget and Matador are available at http://insilico.charite.de/supertarget and http://matador.embl.de...
  26. ncbi Docking and scoring in virtual screening for drug discovery: methods and applications
    Douglas B Kitchen
    Department of Computer Aided Drug Discovery, Albany Molecular Research, Inc, 21 Corporate Circle, Albany, New York 12212 5098, USA
    Nat Rev Drug Discov 3:935-49. 2004
    ..Here, we review key concepts and specific features of small-molecule-protein docking methods, highlight selected applications and discuss recent advances that aim to address the acknowledged limitations of established approaches...
  27. ncbi Soft drug design: general principles and recent applications
    N Bodor
    Center for Drug Discovery, University of Florida, Health Science Center, P O Box 100497, Gainesville, Florida 32610 0497, USA
    Med Res Rev 20:58-101. 2000
    Soft drug design represents a new approach aimed to design safer drugs with an increased therapeutic index by integrating metabolism considerations into the drug design process...
  28. pmc Integrated Modeling Program, Applied Chemical Theory (IMPACT)
    Jay L Banks
    Schrodinger, Inc, New York, NY 10036, USA
    J Comput Chem 26:1752-80. 2005
    ....
  29. ncbi Natural products as leads to potential drugs: an old process or the new hope for drug discovery?
    David J Newman
    Natural Products Branch, Developmental Therapeutics Program, DCTD, National Cancer Institute Frederick, P O Box B, Frederick, Maryland 21702, USA
    J Med Chem 51:2589-99. 2008
  30. pmc Novel inhibitor design for hemagglutinin against H1N1 influenza virus by core hopping method
    Xiao Bo Li
    Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics Theranostics, School of Pharmacy, Tianjin Medical University, Tianjin, China
    PLoS ONE 6:e28111. 2011
    ..to subsequently penetrate into the infected cell, hemagglutinin (HA) has become one of the main targets for drug design against influenza virus...
  31. pmc Small-molecule correctors of defective DeltaF508-CFTR cellular processing identified by high-throughput screening
    Nicoletta Pedemonte
    Department of Medicine, UCSF, San Francisco, California 94143 0521, USA
    J Clin Invest 115:2564-71. 2005
    ..Small-molecule correctors may be useful in the treatment of CF caused by the DeltaF508 mutation...
  32. ncbi Evolutionary and immunological implications of contemporary HIV-1 variation
    B Korber
    Division of Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico 98545, USA
    Br Med Bull 58:19-42. 2001
    ..The impact of HIV-1 variation on host immune response is reviewed in this context...
  33. ncbi The properties of known drugs. 1. Molecular frameworks
    G W Bemis
    Vertex Pharmaceuticals, Cambridge, Massachusetts 02139 4242, USA
    J Med Chem 39:2887-93. 1996
    ..We discuss the possible interpretations of these findings and the way they may be used to guide future drug discovery research...
  34. ncbi Pharmacogenomics: translating functional genomics into rational therapeutics
    W E Evans
    Department of Pharmaceutical Sciences, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Science 286:487-91. 1999
    ....
  35. ncbi Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK)
    J Jean Cui
    La Jolla Laboratories, Pfizer Worldwide Research and Development, San Diego, California 92121, USA
    J Med Chem 54:6342-63. 2011
    ..domain, revealed a novel ATP site environment, which served as the target to guide parallel, multiattribute drug design. A novel 2-amino-5-aryl-3-benzyloxypyridine series was created to more effectively make the key interactions ..
  36. ncbi The cystine knot motif in toxins and implications for drug design
    D J Craik
    Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia
    Toxicon 39:43-60. 2001
    ..and their unique structural scaffold can be harnessed for molecular engineering applications and in drug design. Applications of cystine knot molecules for the treatment of pain, and their potential use in antiviral and ..
  37. pmc Structure and functionality in flavivirus NS-proteins: perspectives for drug design
    Michela Bollati
    Department of Biomolecular Sciences and Biotechnology, University of Milano, Via Celoria 26, 20133 Milano, Italy
    Antiviral Res 87:125-48. 2010
    ..Nevertheless, up to few years ago flaviviruses were considered low interest candidates for drug design. At the start of the European Union VIZIER Project, in 2004, just two crystal structures of protein domains ..
  38. pmc Lessons learnt from assembling screening libraries for drug discovery for neglected diseases
    Ruth Brenk
    University of Dundee, College of Life Sciences, James Black Centre, Dow Street, Dundee DD1 5EH, UK
    ChemMedChem 3:435-44. 2008
    ..The implications of this study for compound selection, especially in an academic environment with limited resources, are considered...
  39. ncbi The resurgence of covalent drugs
    Juswinder Singh
    Avila Therapeutics, 100 Beaver Street, Waltham, Massachusetts 02453, USA
    Nat Rev Drug Discov 10:307-17. 2011
    ....
  40. pmc High-throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv
    Subramaniam Ananthan
    Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA
    Tuberculosis (Edinb) 89:334-53. 2009
    ..taacf.org), a large, medicinally relevant chemical library was screened against M. tuberculosis strain H37Rv. The screening methods and a medicinal chemistry analysis of the results are reported herein...
  41. ncbi Ligand-based dual target drug design for H1N1: swine flu--a preliminary first study
    Chien yu Chen
    Laboratory of Pharmacoinformatics and Nanotechnology Department of Biological Science and Technology, China Medical University Taichung, 40402, Taiwan
    J Biomol Struct Dyn 27:171-8. 2009
    ..Nevertheless, the present study is clear, consistent and could give a rational explanation for the binding mode of the best selected ligand...
  42. pmc Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt Medical Center, 1215 Light Hall, Nashville, Tennessee 37232, USA
    Nat Rev Drug Discov 8:41-54. 2009
    ..These compounds provide high selectivity, novel modes of efficacy and may lead to novel therapeutic agents for the treatment of multiple psychiatric and neurological human disorders...
  43. ncbi Metabonomics: a platform for studying drug toxicity and gene function
    Jeremy K Nicholson
    Biological Chemistry Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, South Kensington, London SW7 2AZ, UK
    Nat Rev Drug Discov 1:153-61. 2002
    ..Metabonomics is a systems approach for studying in vivo metabolic profiles, which promises to provide information on drug toxicity, disease processes and gene function at several stages in the discovery-and-development process...
  44. pmc Antibiotics for emerging pathogens
    Michael A Fischbach
    Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 325:1089-93. 2009
    ....
  45. ncbi Comparative assessment of scoring functions on a diverse test set
    Tiejun Cheng
    State Key Laboratory of Bioorganic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, P R China
    J Chem Inf Model 49:1079-93. 2009
    Scoring functions are widely applied to the evaluation of protein-ligand binding in structure-based drug design. We have conducted a comparative assessment of 16 popular scoring functions implemented in main-stream commercial software or ..
  46. ncbi Further development and validation of empirical scoring functions for structure-based binding affinity prediction
    Renxiao Wang
    Medical Chemistry and Comprehensive Cancer Center, University of Michigan, Ann Arbor 48109 0934, USA
    J Comput Aided Mol Des 16:11-26. 2002
    ..Our results show that this consensus scoring function improves the docking accuracy considerably when compared to the conventional force field computation used for molecular docking...
  47. ncbi Transient pockets on protein surfaces involved in protein-protein interaction
    Susanne Eyrisch
    Center for Bioinformatics, Building C7 1, P O Box 151150, D 66041 Saarbruecken, Germany
    J Med Chem 50:3457-64. 2007
    ....
  48. ncbi Therapeutic potential of venom peptides
    Richard J Lewis
    Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Australia
    Nat Rev Drug Discov 2:790-802. 2003
    ..Here we survey the pharmacology of venom peptides and assess their therapeutic prospects...
  49. ncbi Escape from flatland: increasing saturation as an approach to improving clinical success
    Frank Lovering
    Wyeth Research, Chemical Sciences, Cambridge, Massachusetts 02140, USA
    J Med Chem 52:6752-6. 2009
    ..In an attempt to explain these observations, we further demonstrate that saturation correlates with solubility, an experimental physical property important to success in the drug discovery setting...
  50. ncbi Subcellular targeting strategies for drug design and delivery
    Lawrence Rajendran
    Systems and Cell Biology of Neurodegeneration, Division of Psychiatry Research, University of Zurich, Zurich, Switzerland
    Nat Rev Drug Discov 9:29-42. 2010
    Many drug targets are localized to particular subcellular compartments, yet current drug design strategies are focused on bioavailability and tissue targeting and rarely address drug delivery to specific intracellular compartments...
  51. ncbi Calculation of protein-ligand binding affinities
    Michael K Gilson
    Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA
    Annu Rev Biophys Biomol Struct 36:21-42. 2007
    ..Ultimately, major improvements in modeling accuracy will likely require advances on multiple fronts, as well as continued validation against experiment...
  52. pmc DrugBank: a comprehensive resource for in silico drug discovery and exploration
    David S Wishart
    Department of Computing Science, University of Alberta, Edmonton, AB, Canada T6G 2E8
    Nucleic Acids Res 34:D668-72. 2006
    ..Potential applications of DrugBank include in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical ..
  53. pmc Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus
    John J Dwyer
    Trimeris Inc, 3500 Paramount Parkway, Morrisville, NC 27560, USA
    Proc Natl Acad Sci U S A 104:12772-7. 2007
    ..The potent antiviral activity against resistant viruses, the difficulty in generating resistant virus, and the extended half-life in vivo make this class of fusion inhibitor peptide attractive for further development...
  54. ncbi Structural biology of insulin and IGF1 receptors: implications for drug design
    Pierre De Meyts
    Receptor Biology Laboratory, Hagedorn Research Institute, Niels Steensens Vej 6, DK 2820 Gentofte, Denmark
    Nat Rev Drug Discov 1:769-83. 2002
    ....
  55. ncbi Intramolecular hydrogen bonding in medicinal chemistry
    Bernd Kuhn
    Discovery Chemistry, F Hoffmann La Roche AG, CH 4070 Basel, Switzerland
    J Med Chem 53:2601-11. 2010
    ..A number of general guidelines for medicinal chemists emerge from this study...
  56. pmc An introduction to QT interval prolongation and non-clinical approaches to assessing and reducing risk
    Chris E Pollard
    Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, Cheshire, UK
    Br J Pharmacol 159:12-21. 2010
    ..The non-clinical data are essential to inform decisions about compound progression and to optimize the design of clinical QT studies...
  57. ncbi Similarity-based virtual screening using 2D fingerprints
    Peter Willett
    Krebs Institute for Biomolecular Research and Department of Information Studies, University of Sheffield, 211 Portobello, Sheffield S1 4DP, UK
    Drug Discov Today 11:1046-53. 2006
    ..We demonstrate the effectiveness of this approach to screening, and also describe an approximate form of group fusion, turbo similarity searching, that can be used when just a single reference structure is available...
  58. ncbi HIV vaccine design and the neutralizing antibody problem
    Dennis R Burton
    Departments of Immunology and Molecular Biology, Scripps Research Institute, La Jolla, California, USA
    Nat Immunol 5:233-6. 2004
  59. ncbi Structural biology in fragment-based drug design
    Christopher W Murray
    Astex Therapeutics Ltd, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom
    Curr Opin Struct Biol 20:497-507. 2010
    ..We focus on antimicrobial research where fragment-based drug discovery allows control of the physical properties of the emerging lead molecule...
  60. ncbi ADMET in silico modelling: towards prediction paradise?
    Han van de Waterbeemd
    Pfizer Global Research and Development, PDM, Sandwich, Kent CT13 9NJ, UK
    Nat Rev Drug Discov 2:192-204. 2003
    ..Here, we describe how in silico approaches will further increase our ability to predict and model the most relevant pharmacokinetic, metabolic and toxicity endpoints, thereby accelerating the drug discovery process...
  61. ncbi The many roles of computation in drug discovery
    William L Jorgensen
    Department of Chemistry, Yale University, New Haven, CT 06520 8107, USA
    Science 303:1813-8. 2004
    ..Particular emphasis is placed on virtual screening, de novo design, evaluation of drug-likeness, and advanced methods for determining protein-ligand binding...
  62. ncbi Multi-target therapeutics: when the whole is greater than the sum of the parts
    Grant R Zimmermann
    CombinatoRx Inc, 245 First Street, Cambridge, MA 02142, USA
    Drug Discov Today 12:34-42. 2007
    ....
  63. ncbi Novel computational approaches to polypharmacology as a means to define responses to individual drugs
    Lei Xie
    Department of Computer Science, Hunter College, The City University of New York, New York, New York 10065, USA
    Annu Rev Pharmacol Toxicol 52:361-79. 2012
    ..Although such is a future objective, we review recent progress and challenges in computational techniques that enable the prediction and analysis of in vitro and in vivo drug-response phenotypes...
  64. ncbi A semiempirical free energy force field with charge-based desolvation
    Ruth Huey
    Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92102, USA
    J Comput Chem 28:1145-52. 2007
    ..The force field shows improvement in redocking simulations over the previous AutoDock3 force field...
  65. pmc Structure of protein interaction networks and their implications on drug design
    Takeshi Hase
    Department of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo ku, Tokyo, Japan
    PLoS Comput Biol 5:e1000550. 2009
    ..Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects...
  66. ncbi Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design
    Paul G Wyatt
    Astex Therapeutics Ltd, 436 Cambridge Science Park, Milton Road, Cambridge, CB4 0QA, United Kingdom
    J Med Chem 51:4986-99. 2008
    ..Optimisation of cellular activity and characterization of pharmacokinetic properties led to the identification of 33 (AT7519), which is currently being evaluated in clinical trials for the treatment of human cancers...
  67. pmc Structural basis for understanding oncogenic p53 mutations and designing rescue drugs
    Andreas C Joerger
    Cambridge University Chemical Laboratory and Cambridge Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom
    Proc Natl Acad Sci U S A 103:15056-61. 2006
    ..g., temperature sensitivity). Some mutants have the potential of being rescued by a generic stabilizing drug. In addition, a mutation-induced crevice is a potential target site for a mutant-selective stabilizing drug...
  68. ncbi The state of the art in anti-malarial drug discovery and development
    Jeremy N Burrows
    Medicines for Malaria Venture, ICC, Geneva, Switzerland
    Curr Top Med Chem 11:1226-54. 2011
    ..This review summarises the antimalarials developed and registered thus far, as well as describing some of the new small molecule therapy approaches being developed as a contribution towards the malaria eradication agenda...
  69. ncbi Atomic interactions and profile of small molecules disrupting protein-protein interfaces: the TIMBAL database
    Alicia P Higueruelo
    Department of Biochemistry, University of Cambridge, UK
    Chem Biol Drug Des 74:457-67. 2009
    ..The database provides a resource that will allow further insights into the types of molecules favoured by protein interfaces and provide a background to continuing work in this area. Access at http://www-cryst.bioc.cam.ac.uk/timbal...
  70. ncbi Surflex-Dock 2.1: robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search
    Ajay N Jain
    Department of Biopharmaceutical Sciences, UCSF Cancer Research Institute, University of California San Francisco, Box 0128, San Francisco, CA 94143 0128, USA
    J Comput Aided Mol Des 21:281-306. 2007
    ....
  71. ncbi Combining docking and molecular dynamic simulations in drug design
    Hernán Alonso
    Computational Proteomics Group, John Curtin School of Medical Research, The Australian National University, Canberra ACT 0200, Australia
    Med Res Rev 26:531-68. 2006
    ..Despite a shaky early history, computer-aided drug design techniques can now be effective in reducing costs and speeding up drug discovery...
  72. ncbi From in silico target prediction to multi-target drug design: current databases, methods and applications
    Alexios Koutsoukas
    Unilever Centre for Molecular Sciences Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom
    J Proteomics 74:2554-74. 2011
    ..Finally, we will conclude with the prospective application of databases to not only predict, retrospectively, the protein targets of a small molecule, but also how to design ligands with desired polypharmacology in a prospective manner...
  73. ncbi Amphipathic alpha helical antimicrobial peptides
    A Giangaspero
    Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, Italy
    Eur J Biochem 268:5589-600. 2001
    ..The simple guidelines obtained in this study allowed the design of highly active shortened AMPs and may be generally useful in the development of this type of peptides as anti-infective agents...
  74. pmc Enterovirus 71 and coxsackievirus A16 3C proteases: binding to rupintrivir and their substrates and anti-hand, foot, and mouth disease virus drug design
    Guangwen Lu
    Chinese Academy of Sciences, Beijing 100101, China
    J Virol 85:10319-31. 2011
    ..In conclusion, the detailed characterization of both proteases in this study could direct us to a proposal for rational design of EV71/CVA16 3C inhibitors...
  75. ncbi G-quadruplexes: targets in anticancer drug design
    Tian Miao Ou
    School of Pharmaceutical Science, Sun Yat Sen University, Guangzhou 510080, People s Republic of China
    ChemMedChem 3:690-713. 2008
    ..As drug design targets, the topology and structural characteristics of quadruplexes, their possible biological roles, and the ..
  76. pmc Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria
    Richard T Eastman
    Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, Hammer Health Sciences Center, Room 1502, 701 West 168th Street, New York 10032, New York, USA
    Nat Rev Microbiol 7:864-74. 2009
    ..This Review article discusses our current knowledge about the mode of action of ACTs, their pharmacological properties and the proposed mechanisms of drug resistance...
  77. ncbi Improved therapeutic targeting of the androgen receptor: rational drug design improves survival in castration-resistant prostate cancer
    Ai Chiin Lim
    Section of Medicine, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, United Kingdom
    Curr Drug Targets 14:408-19. 2013
    ..Rationally-designed approaches combining different strategies for targeting the AR or associated pathways also warrant clinical evaluation...
  78. ncbi Structure-based and ligand-based drug design for HER 2 receptor
    Hung jin Huang
    Laboratory of Computational and Systems Biology, School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan, ROC
    J Biomol Struct Dyn 28:23-37. 2010
    ..In this study, both structure-based and ligand-based drug design were employed to design novel HER2 inhibitors from traditional Chinese medicine (TCM)...
  79. doi Recent developments in fragment-based drug discovery
    Miles Congreve
    Astex Therapeutics Ltd, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK
    J Med Chem 51:3661-80. 2008
  80. ncbi 970 million druglike small molecules for virtual screening in the chemical universe database GDB-13
    Lorenz C Blum
    Department of Chemistry and Biochemistry, University of Berne, Freiestrasse 3, CH 3012 Berne, Switzerland
    J Am Chem Soc 131:8732-3. 2009
    ..With 977,468,314 structures, GDB-13 is the largest publicly available small organic molecule database to date...
  81. ncbi Binding properties of human telomeric quadruplex multimers: a new route for drug design
    Annunziata Cummaro
    Department of Chemistry P Corradini, University of Naples Federico II, Via Cintia, 4, I 80126 Napoli, Italy
    Biochimie 93:1392-400. 2011
    ..The existence of quadruplex-quadruplex interfaces in the full length telomeric overhang may provide an advantageous factor in drug design to enhance both affinity and selectivity for DNA telomeric quadruplexes.
  82. ncbi Scoring functions and their evaluation methods for protein-ligand docking: recent advances and future directions
    Sheng You Huang
    Department of Physics and Astronomy, Department of Biochemistry, Dalton Cardiovascular Research Center, and Informatics Institute, University of Missouri, Columbia, MO 65211, USA
    Phys Chem Chem Phys 12:12899-908. 2010
    The scoring function is one of the most important components in structure-based drug design. Despite considerable success, accurate and rapid prediction of protein-ligand interactions is still a challenge in molecular docking...
  83. ncbi MIND-BEST: Web server for drugs and target discovery; design, synthesis, and assay of MAO-B inhibitors and theoretical-experimental study of G3PDH protein from Trichomonas gallinae
    Humberto Gonzalez-Diaz
    Department of Microbiology and Parasitology, University of Santiago de Compostela, Spain
    J Proteome Res 10:1698-718. 2011
    ..and MAO-A and MAO-B pharmacological assay of eight rasagiline derivatives, promising for anti-Parkinson drug design. In experiment 2, we report sampling, parasite culture, sample preparation, 2-DE, MALDI-TOF and -TOF/TOF MS, ..
  84. ncbi Recent progress in fragment-based lead discovery
    Michèle N Schulz
    YSBL, University of York, York YO10 5YW, United Kingdom
    Curr Opin Pharmacol 9:615-21. 2009
    ..Here, we provide a brief summary of the key elements of fragment-based lead discovery (FBLD), review recent progress and provide a perspective on the challenges that remain for the field...
  85. pmc Crystal engineering of HIV-1 reverse transcriptase for structure-based drug design
    Joseph D Bauman
    Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ, USA
    Nucleic Acids Res 36:5083-92. 2008
    ..The new RTs enable rapid crystallization and yield high-resolution structures that are useful in designing/developing new anti-AIDS drugs...
  86. pmc Computer-aided drug-discovery techniques that account for receptor flexibility
    Jacob D Durrant
    Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA
    Curr Opin Pharmacol 10:770-4. 2010
    ....
  87. ncbi Casein Kinase II: an attractive target for anti-cancer drug design
    Ismail Muhamad Hanif
    Experimental Therapeutics Centre, Agency for Science, Technology and Research A STAR, Singapore
    Int J Biochem Cell Biol 42:1602-5. 2010
    ..Here we provide a succinct account of the biology of CK2, its cellular substrates, its pro-survival and pro-proliferation activity, and highlight evidence for its involvement in human cancer...
  88. pmc Customizing scoring functions for docking
    Tuan A Pham
    University of California, San Francisco, Box 0128, San Francisco, CA 94143 0128, USA
    J Comput Aided Mol Des 22:269-86. 2008
    ..Analysis of the changes to the scoring function suggest that modifications can be learned that are related to protein-specific features such as active-site mobility...
  89. ncbi Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery
    Stéphanie Pérot
    Universite Paris Diderot, 75013 Paris, France
    Drug Discov Today 15:656-67. 2010
    Detection, comparison and analyses of binding pockets are pivotal to structure-based drug design endeavors, from hit identification, screening of exosites and de-orphanization of protein functions to the anticipation of specific and non-..
  90. ncbi Structure of a human Tcf4-beta-catenin complex
    F Poy
    Department of Cancer Biology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Nat Struct Biol 8:1053-7. 2001
    ..The structure reveals anticipated similarities with the closely related XTcf3 complex but unexpectedly lacks one component observed in the XTcf3 structure...
  91. ncbi The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design
    Rupert J Russell
    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Nature 443:45-9. 2006
    ..Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs...
  92. ncbi Drug design against a shifting target: a structural basis for resistance to inhibitors in a variant of influenza virus neuraminidase
    J N Varghese
    Biomolecular Research Institute 343 Royal Parade, Parkville, 3052, Australia
    Structure 6:735-46. 1998
    ..This study seeks to clarify the structural and functional consequences of replacing the glycerol sidechain of the inhibitor with other chemical constituents...
  93. ncbi Molecule-pharmacophore superpositioning and pattern matching in computational drug design
    Gerhard Wolber
    Inte Ligand GmbH, Mariahilferstrasse 74B 11, 1070 Vienna, Austria
    Drug Discov Today 13:23-9. 2008
    ....
  94. ncbi Functionalized carbon nanotubes in drug design and discovery
    Maurizio Prato
    Dipartimento di Scienze Farmaceutiche, Universita di Trieste, 34127 Trieste, Italy
    Acc Chem Res 41:60-8. 2008
    ....
  95. ncbi Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry
    Miklos Feher
    SignalGene Inc, 335 Laird Road, Unit 2, Guelph, Ontario, N1G 4P7, Canada
    J Chem Inf Comput Sci 43:218-27. 2003
    ..It is suggested that by mimicking certain distribution properties of natural compounds, combinatorial products might be made that are substantially more diverse and have greater biological relevance...
  96. ncbi Molecular lipophilicity in protein modeling and drug design
    Roman G Efremov
    M M Shemyakin and Yu A Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul Miklukho Maklaya, 16 10, Moscow V 437, 117997 GSP, Russia
    Curr Med Chem 14:393-415. 2007
    ..properties of these molecules is indispensable for the development of efficient computational methods in drug design. One possible solution to the problem lies in application of a concept of the 3-dimensional molecular ..
  97. ncbi Definition of the G protein-coupled receptor transmembrane bundle binding pocket and calculation of receptor similarities for drug design
    David E Gloriam
    Department of Medicinal Chemistry, Pharmaceutical Faculty, Copenhagen University, Universitetsparken 2, 2100 Copenhagen, Denmark
    J Med Chem 52:4429-42. 2009
    ..This has wide applicability to GPCR drug design problems across many disease areas.
  98. pmc Design of polymeric nanoparticles for biomedical delivery applications
    Mahmoud Elsabahy
    Department of Chemistry, Texas A and M University, P O Box 30012, 3255 TAMU, College Station, Texas 77842 3012, USA
    Chem Soc Rev 41:2545-61. 2012
    ..This tutorial review highlights the importance of well-defined chemistries, with detailed ties to specific biological hurdles and opportunities, in the design of nanostructures for various biomedical delivery applications...
  99. ncbi Computational drug design targeting protein-protein interactions
    Rachelle J Bienstock
    National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Curr Pharm Des 18:1240-54. 2012
    ..area, can comprise a discontinuous epitope, and is more amorphous and less well defined than the typical drug design target, a small contained enzyme-binding pocket...
  100. pmc A new drug design targeting the adenosinergic system for Huntington's disease
    Nai Kuei Huang
    National Research Institute of Chinese Medicine, Taipei, Taiwan
    PLoS ONE 6:e20934. 2011
    ..The expanded CAG repeats are translated into polyglutamine (polyQ), causing aberrant functions as well as aggregate formation of mutant Htt. Effective treatments for HD are yet to be developed...
  101. pmc Protein-ligand interaction prediction: an improved chemogenomics approach
    Laurent Jacob
    Mines ParisTech, Centre for Computational Biology, 35 rue Saint Honore, F 77305 Fontainebleau, Institut Curie and INSERM, U900, F 75248, Paris, France
    Bioinformatics 24:2149-56. 2008
    ..However, the accuracy of ligand-based models quickly degrades when the number of known ligands decreases, and in particular the approach is not applicable for orphan receptors with no known ligand...

Research Grants76

  1. Nanoliter Lab-on-a-chip for Protein Crystallization
    Vamsee Pamula; Fiscal Year: 2007
    ..to determine their 3D structure which needs to be understood for any effective protein engineering, rational drug design, or controlled drug delivery...
  2. STRUCTURE-BASED TUBERCULOSIS DRUG DESIGN TARGETED AT ACYL-COA CARBOXYLASE
    Shiou Chuan Tsai; Fiscal Year: 2010
    ..PERFORMANCE SITE(S) (organization, city, state) University of California, Irvine, CA 92697, USA REVISED ABSTRACT SECTION ..
  3. Structural and molecular basis of drug-induced IKACh reduction
    SAMI FOUAD NOUJAIM; Fiscal Year: 2013
    ..antiarrhythmic drug-ion channel interactions remain poorly understood, and that incomplete knowledge and poor drug design may underlie the inefficacy of currently available antiarrhythmics. The Kir3.1 and Kir3...
  4. Structural and molecular basis of drug-induced IKACh reduction
    SAMI FOUAD NOUJAIM; Fiscal Year: 2012
    ..antiarrhythmic drug-ion channel interactions remain poorly understood, and that incomplete knowledge and poor drug design may underlie the inefficacy of currently available antiarrhythmics. The Kir3.1 and Kir3...
  5. Characterization of new toxins (YmgD and YdfD) from E.coli, targeting cell wall
    Hisako Masuda; Fiscal Year: 2012
    ..cell wall and cause rapid cell lysis, our investigation will directly provide us a new means to examine the basic biology of cell wall biosynthesis, and will reveal a new target of drug design and also lead to develop novel antibiotics.
  6. Deacetylation of mitochondrial proteins protect neurons from ischemic injury
    Conrad Alano; Fiscal Year: 2013
    ..to identify and characterize the protective effect of Sirt3 in order to identify small molecule modulators and drug design for treatment intervention...
  7. Varicella zoster virus: molecular controls of cell fusion-dependent pathogenesis
    Ann Arvin; Fiscal Year: 2013
    ..of polykaryocyte formation for pathogenesis, deciphering how VZV regulates this process has the potential to yield new strategies for vaccine virus attenuation and antiviral drug design to ease the burden on vulnerable populations.
  8. Inhibitors of S. aureus bNOS for adjunctive therapy
    Donald T Moir; Fiscal Year: 2013
    ..most promising validated hits into lead compounds by optimizing their activity and specificity using rational drug design and evaluate them for efficacy and toxicity in animal models of infection...
  9. X-ray Studies of Sugar-Modifying Enzymes
    Hazel Holden; Fiscal Year: 2013
    ..Some of the proteins in these biosynthetic pathways may ultimately serve as targets for antimicrobial drug design. In addition, the proposed investigations will reveal unprecedented chemistries and will provide fundamental ..
  10. Development of inhibitors of AMP Deaminase Isoform 2 as a Mechanism for Treating
    RICHARD JOSEPH JOHNSON; Fiscal Year: 2010
    ..By combining the expertise of the basic science laboratory of Dr. Johnson with the highly experienced drug design team from Amidaerus, we expect to develop the first AMPD2 inhibitor that will be ready for Phase I trials at ..
  11. Structure and function of chloride channels and transporters
    Alessio Accardi; Fiscal Year: 2013
    ..and pathological processes marks them as ideal targets for the development of therapeutic treatments and drug design. This progress is, however, stunted by our lack of knowledge of the basic structural and mechanistic ..
  12. The role fo the TPP1 peotein in telomerase function and cancer cell survival
    Jayakrishnan Nandakumar; Fiscal Year: 2013
    ..somatic cells, but is overexpressed in 90% of cancer cells, it serves as an attractive target for anti-cancer drug design. A multi- protein complex known as shelterin associates specifically with telomeric DNA to repress illicit DNA ..
  13. Novel Small Molecules For Acute Liver Failure
    Prakash Narayan; Fiscal Year: 2009
    ..the SF/HGF receptor c-Met's tyrosine kinase domain and using a product discovery engine combining rational drug design with preclinical biology, we have identified SF/HGF-like small molecules centered around a phthalazin-1 (2H)- ..
  14. Using PET isotopes to identify drug targets and to diagnose infectious diseases
    Peter J Tonge; Fiscal Year: 2010
    ..order to create affinity matrices or photoaffinity labels, and will provide critical information for rational drug design. The use of PET radioisotopes has several advantages compared to methods that relay on conventional radiolabels ..
  15. Oxidative Stress: A Recipe for Anxiety
    Samina Salim; Fiscal Year: 2012
    ..Mechanistic insights obtained from our proposal would lead to the identification of novel targets for drug design in the treatment of anxiety disorders...
  16. Transferrin Conjugates for Oral Protein Drug Delivery
    Wei Chiang Shen; Fiscal Year: 2013
    ..This proposal utilizes a fusion protein drug design for oral delivery based on transferrin (Tf) receptor (TfR)-mediated transcytosis in intestinal epithelial cells,..
  17. Enzymology of Post-translational Modifications
    Carol A Fierke; Fiscal Year: 2013
    ..Overall, our studies will assist in targeted drug design by describing the specific interactions that dictate substrate specificity and by identifying novel regulatory ..
  18. TAM receptor tyrosine kinases in inflammatory bowel disease
    Carla Rothlin; Fiscal Year: 2013
    ..class of enzymes that are well established as tractable pharmacological targets and are attractive for rational drug design and discovery...
  19. Separation-of-function Mutants to Study the Biological Significance of Telomerase
    Jayakrishnan Nandakumar; Fiscal Year: 2012
    ..somatic cells, but is overexpressed in 90% of cancer cells, it serves as an attractive target for anti-cancer drug design. A multi- protein complex known as shelterin associates specifically with telomeric DNA to repress illicit DNA ..
  20. Blood Pressure -- Determinants &Controllers
    Allen W Cowley; Fiscal Year: 2012
    ..reflects a long-standing experience of shared ideas in a synergistic environment aimed toward advancing our understanding of hypertension and the identification of novel targets for drug design that may better control this disease.
  21. Targeted epigenetic silencing of oncogenic Transcription Factors (PQ18)
    Pilar Blancafort; Fiscal Year: 2013
    ..enzymatic activities and they lack small-molecule-binding pockets, these targets have been refractory to drug design. The oncogenic TFs Sox2 is over-expressed in breast cancers of advanced stage, while the gene is silenced and ..
  22. Development of Small Antimicrobial Peptide Mimics as Drug-Resistant and Susceptib
    Richard W Scott; Fiscal Year: 2013
    ..Therefore, it is crucial to discover new classes of drugs for anti-malarial drug design to combat resistant parasites...
  23. Novel Compounds to Inactivate Oncogenic Fusion Proteins
    Jeffrey A Toretsky; Fiscal Year: 2013
    ..Disordered proteins lack the rigid alpha-helical or beta sheet structures required for structure-based drug design. While disordered proteins require a more empiric approach to the discovery of small molecule protein-protein ..
  24. Rational Development of Anti-Trypanosoma Cruzi Drugs
    Michael H Gelb; Fiscal Year: 2013
    ..The group of scientists consisting of Drs. Buckner (biology), Gelb (chemistry), and Verlinde (structure-based drug design) has worked as a team on antiparasitic drug development for ~15 years with collectively >100 published ..
  25. Investigating SloR virulence gene metalloregulation in S. mutans.
    Grace A Spatafora; Fiscal Year: 2013
    ..environment, particularly iron and manganese, metal ion uptake mechanisms represent attractive targets for drug design aimed at combating cavities...
  26. Improved idiotype immunotherapy for lymphoma by RNA vaccine delivery
    ALISON ANNE MCCORMICK; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: Improving cancer vaccine therapy by rational drug design is a high priority of research scientists and the medical community...
  27. Novel lead molecule optimization targeting nicotinic receptor subtypes
    DENNIS BRIAN contact MCKAY; Fiscal Year: 2010
    ..Our target is the neuronal nicotinic acetylcholine receptor (nAChR). Structure-based drug design as a "rational" method has been quite successful, contributing to the introduction of ~50 compounds into ..
  28. Development of Inhibitors of the Leukemia Fusion Protein CBFbeta-SMMHC
    Roger A Rajewski; Fiscal Year: 2013
    ..We are proposing to further optimize the potency of this lead using structure-based drug design and medicinal chemistry approaches...
  29. Control of cAMP Mediated Glucagon Response by Bile Acids
    Norman H Lee; Fiscal Year: 2011
    ..and activation of PKC may have the added benefit of identifying novel molecular targets for rational drug design in the treatment of cholestatic hepatobiliary disorders, as well as diabetes...
  30. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2009
    ..There is good evidence that the polyamine biosynthetic pathway is a valid target for drug design. The planned experiments focus on studies of the synthesis, function and regulation of spermine levels in ..
  31. Pharmacology of Intravesical Antisense Based Therapy for Over Active Bladder
    Naoki Yoshimura; Fiscal Year: 2013
    ..gene-silencing mechanism is a promising approach for developing therapeutics agent based on rational gene-based drug design. In the current proposal, we propose to use this approach for silencing nerve growth factor (NGF) gene locally ..
  32. Investigating SloR virulence gene metalloregulation in S. mutans.
    Grace Spatafora; Fiscal Year: 2009
    ..environment, particularly iron and manganese, metal ion uptake mechanisms represent attractive targets for drug design aimed at combating cavities...
  33. Discovery of novel anti-HBV compounds targeting host factors
    Pavel A Petukhov; Fiscal Year: 2013
    ..of approaches: high- throughput screening (HTS) against HBV nucleocapsid promoter activity, computer-aided drug design (CADD), chemical biology, target identification methods, target-oriented rational drug design, medicinal ..
  34. Structural Rearrangements in GABA-A Receptors
    CYNTHIA M CZAJKOWSKI; Fiscal Year: 2012
    ....
  35. Structure-Function of the Shigella dysenteriae heme uptake operon (shu)
    Angela Wilks; Fiscal Year: 2012
    ..uptake and utilization in gram-negative pathogens as a step toward identifying therapeutic targets for future drug design and development...
  36. Identification of G6PD inhibitors for the development of novel antimalarial drugs
    Lars Bode; Fiscal Year: 2010
    ..Glucose-6-phosphate dehydrogenase (G6PD) is a novel target for antimalarial drug design based on observations that humans with a genetic deficiency in this enzyme are protected against malaria...
  37. Structural and Biochemical Basis of the Vitamin K cycle
    Weikai Li; Fiscal Year: 2013
    ..The studies will provide the basis for rational drug design. 2) We will determine structures of reaction intermediates to elucidate the pathway by which electrons flow ..
  38. Structural Genomics of Orphan Nuclear Receptors
    H Eric Xu; Fiscal Year: 2013
    ..these orphan nuclear receptors are ligand-regulated receptors, but will also serve as a rational template for drug design targeting of these receptors for cancers, metabolic diseases, and stem cell therapy for neurodegenerative ..
  39. Pneumocystis jirovecii Targeted Antiopportunistic Agents
    Aleem Gangjee; Fiscal Year: 2013
    ..determine the structural requirements for potent and selective inhibition of pjDHFR and will assist in future drug design and pharmacophore generation...
  40. The Mycobacterium Tuberculosis Dormancy Program
    MARTIN INUA VOSKUIL; Fiscal Year: 2013
    ..protocol and our limited understanding of relevant intermediary metabolic pathways limit a rational approach to drug design. Our preliminary data suggests we are at the brink of a fundamental understanding of Mtb anaerobic metabolism...
  41. Transport and Inhibition in a Biogenic Amine Transporter
    SATINDER KAUR SINGH; Fiscal Year: 2012
    ..binding sites and perhaps into the molecular basis for drug resistance, thereby opening the way to rational drug design efforts...
  42. Transport and Inhibition in a Biogenic Amine Transporter
    Satinder Singh; Fiscal Year: 2009
    ..binding sites and perhaps into the molecular basis for drug resistance, thereby opening the way to rational drug design efforts...
  43. The Role of the Central Melanocortin System in the Muscle Wasting of Cachexia
    THEODORE PAUL BRAUN; Fiscal Year: 2013
    ..A mechanistic understanding of this pathway will provide insight into the care of these patients and provide future targets for rational drug design.
  44. Matrix Metalloproteinase Inhibitors in Stroke
    GARY ALLEN ROSENBERG; Fiscal Year: 2010
    ..This proposal will combine the resources of experts in MMPI drug design and measurements of BBB damage in vivo and will utilize start-of-art MRI technology to identify the most ..
  45. CNS Delivery of Activated Antiviral Drugs with Reduced Neurotoxicity (Nano-NRTIs)
    Serguei V Vinogradov; Fiscal Year: 2013
    ..To address this hypothesis, we propose the following Specific aims: (1) to apply rational drug design and nanoengineering to the construction of nanocarriers loaded with pNRTI;(2) to optimize the antiviral effect ..
  46. Deciphering the Mechanism of Transporters by Design and Experiments
    HYUN JOONG CHO; Fiscal Year: 2013
    ..as well as fundamental to addressing relevant questions, such as disease etiology at the molecular level and drug design. Despite the importance, efforts to gain structural understanding of transport mechanism have long been ..
  47. Biochemistry of recombination in gametogenesis
    Wayne P Wahls; Fiscal Year: 2010
    ..They will also pave the way for rational drug design and high-throughput screening to identify potential contraceptive agents that affect specifically Rec12-..
  48. ALCOHOL AND CELL ADHESION
    MICHAEL EDWARD CHARNESS; Fiscal Year: 2013
    ..women who drink during pregnancy to bear children with FASD;and to provide a scientific foundation for rational drug design to prevent or mitigate FASD...
  49. Nitroalkene-Mediated Vascular Protection and Ischemic Stroke
    Yuqing Eugene Chen; Fiscal Year: 2013
    ..to a better understanding of endogenous signaling actions of nitroalkenes in ischemic stroke and will set strong basis for new perspectives on rational drug design and development of nitroalkene derivatives for the treatment of stroke.
  50. The Effect of Genetic Diversity on Mechanism-Based Inactivation of CYP2D6
    Laura L Furge; Fiscal Year: 2013
    ..studies will provide an understanding of how in activators interact with CYP2D6 and lead to new opportunities in rational drug design and evaluation of inter-individual differences in drug metabolism in the age of personalized medicine.
  51. Novel Topoisomerase I Inhibitors
    MARK S CUSHMAN; Fiscal Year: 2013
    ..be aided by crystallography inhibitor/enzyme/DNA of ternary complexes, which will facilitate structure-based drug design. A variety of synthetic methods will be employed in the syntheses of new Top I inhibitors, including ..
  52. HDAC Inhibitors Inspired by Natural Products
    Dennis L Wright; Fiscal Year: 2012
    ..These studies will ultimately support a structure-based drug design effort as we move forward with lead optimization...
  53. Age-Dependent Mechanisms in Thoracic Aortic Aneurysms
    John S Ikonomidis; Fiscal Year: 2013
    ..provide significant insight toward understanding the pathophysiology of TAA development, and will form the basis for novel, rational drug design for therapeutic modulation of TAA progression in patients with this devastating disease.
  54. MECHANISM OF CANALICULAR BILE FORMATION AND CHOLESTASIS
    MOHAMMED SAWKAT ANWER; Fiscal Year: 2010
    ..in an isoform specific manner, a better understanding of isoform specific effects should allow for a better drug design that could avoid potential liver toxicity...
  55. Mechanisms of receptor protein tyrosine phosphatase signaling in Drosophila devel
    Jessica E Treisman; Fiscal Year: 2013
    ..conservation of the components suggests that our results will be applicable to higher organisms, and may guide drug design to treat human diseases caused by receptor tyrosine phosphatase dysfunction such as cancer, diabetes and ..
  56. Chemical biology of voltage-gated sodium and potassium channels
    Christopher A Ahern; Fiscal Year: 2013
    ..a significant block to our understanding of ion permeation and channel gating, and ultimately, effective drug design. Here we propose to design and apply powerful synthetic tools, in the form of tailor-made unnatural amino acids,..
  57. NF-kappaB N-myc in Oncogenic Pathways of the CNS
    Raquel Sitcheran; Fiscal Year: 2010
    ..These studies have the potential to offer new insight into drug design targeting oncogenic pathways regulated by NF-KB and N-myc.
  58. Characterizing RNA-metal binding by Raman spectroscopy
    Paul R Carey; Fiscal Year: 2012
    ..In the clinical context it is both a target for drug design and a tool for regulating gene function...
  59. Molecular Activities of Angiogenin in the Nucleus
    KIMBERLY ANNE DICKSON; Fiscal Year: 2012
    ..roles in cancer and ALS, yet our meager knowledge of the molecular interactions of ANG is a critical barrier to drug design. The overarching goal of this research is to understand the specific molecular activities of human angiogenin (..
  60. LRH-1: Structure-based Approach to Drug Design for Gastrointestinal Tumors
    James Bayrer; Fiscal Year: 2013
    ..abstract_text> ..
  61. Signaling Crosstalk Controlled by a Mad Phosphoserine Code
    EDWARD V EIVERS; Fiscal Year: 2013
    ..a new complexity between BMP and Wg crosstalk exists, highlighting a further consideration in possible future drug design against either pathway;as targeting one pathway to treat a disease could unintentionally modify the signaling ..
  62. Safe and Efficacious Oral MIF Inhibitors for Rheumatoid Arthritis Treatment
    ANDERSON GAWECO; Fiscal Year: 2012
    ..entities of INV-88 lead scaffolds were discovered in silico using fragment-based coupled with structure-based drug design and are the first oral MIF inhibitors that target critical MIF pharmacophores taking advantage of emerging ..
  63. Trypanosoma cruzi Antioxidant Systems, Virulence and Parasite Persistence in Chag
    Rafael Radi; Fiscal Year: 2013
    ..process, 2) shed light on the contribution of the oxidant-antioxidant balance on parasite control, 3) determine the role of the parasite antioxidant network in disease severity and progression and 4) promote drug design and development.
  64. Development of an Algae-based Membrane Protein Expression System
    ALEXANDER ARAVANIS; Fiscal Year: 2009
    ..opportunities include the use of the system for production of important IMP samples for structure-based drug design (SBDD) studies...
  65. GENETIC ANALYSIS OF PURINE METABOLISM IN LEISHMANIA DONO
    Buddy Ullman; Fiscal Year: 2007
    ..of[unreadable] a rational, structure-based strategy of drug discovery, and ultimately[unreadable] drug design, for the treatment and prevention of leishmaniasis and other[unreadable] diseases of parasitic origin...
  66. Screening for Chemicals that Potentiate TRAIL-Induced Apoptosis of Cancer Cells
    DMITRI ROZANOV; Fiscal Year: 2007
    ..DESCRIPTION (provided by applicant): The purpose of this R03 application is to describe our proposed drug design effort designed to potentiate TRAIL-induced apoptosis in cancer cells...
  67. MOLECULAR RECOGNITION IN THE STREPTAVIDIN BIOTIN SYSTEM
    Patrick Stayton; Fiscal Year: 2001
    ..high- affinity, the principles elucidated here should prove generally useful to the field of structure-based drug design. In order to connect fundamental advances to drug design, the investigators have added a computational ..
  68. MOLECULAR RECOGNITION IN THE STREPTAVIDIN BIOTIN SYSTEM
    Patrick Stayton; Fiscal Year: 2002
    ..high- affinity, the principles elucidated here should prove generally useful to the field of structure-based drug design. In order to connect fundamental advances to drug design, the investigators have added a computational ..
  69. Apparatus for encapsulating integral membrane proteins for structural studies by
    RONALD WILLIAM PETERSON; Fiscal Year: 2010
    ..In the area of medicine and drug design the structure of the protein can greatly facilitate rational design of effective pharmaceuticals...
  70. Small Molecule Inhibitors of Anthrax Lethal Factor
    NORTON PEET; Fiscal Year: 2006
    ..providing a powerful tool, which we will use to guide the inhibitor refinement process through structure-based drug design. The overall goal of this project is to develop a small molecule LF inhibitor to treat anthrax...
  71. DRUG DESIGN FOR TREATING OPPORTUNISTIC INFECTION IN AIDS
    Kurt Krause; Fiscal Year: 2003
    ..These compounds will be engineered in a collaborative structure based drug design program based at the University of Houston...
  72. Targets for Drug Design In Flaviviral Infection
    Kurt Krause; Fiscal Year: 2004
    The broad, long-term objective of this proposal is to lay the foundation for a collaborative structure aided drug design effort aimed at developing lead compounds for flaviviral drug development...
  73. Anti-Cancer Drug Design Targeting Human Topoisomerase I
    Lance Stewart; Fiscal Year: 2002
    ..We now seek Phase 2 SBIR funds to conduct an integrated structure-based drug design cycle using our 2.0 angstrom structural information of Topotecan bound to the human topo I-DNA covalent complex...
  74. Computational Suite for RNA-Targeted Drug Design
    Erin Duffy; Fiscal Year: 2005
    ..Standard regression models will be attempted, and statistical measures will be monitored, focused on the goodness of fit (r2 and q2), the significance of individual molecular descriptors and the variance in the models. ..
  75. Development of Opioid Receptor Models for Rational Design of Bifunctional Ligands
    JUDITH HOBRATH; Fiscal Year: 2009
    ..These drug design efforts could gain a significant advantage if requirements of potent agonist and antagonist binding are ..
  76. THERAPEUTIC NA+ CHANNEL BLOCKERS: RECEPTOR & DRUG DESIGN
    GING WANG; Fiscal Year: 2007
    ..This information will in turn facilitate receptor-based drug design. Together, these studies should provide us new lead structures for the development of long-acting LAs that ..