azepines

Summary

Summary: Seven membered heterocyclic rings containing a NITROGEN atom.

Top Publications

  1. pmc Targeting MYC dependence in cancer by inhibiting BET bromodomains
    Jennifer A Mertz
    Constellation Pharmaceuticals, Inc, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 108:16669-74. 2011
  2. pmc Targeting MYCN in neuroblastoma by BET bromodomain inhibition
    Alexandre Puissant
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA
    Cancer Discov 3:308-23. 2013
  3. pmc Small-molecule inhibition of BRDT for male contraception
    Martin M Matzuk
    Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA
    Cell 150:673-84. 2012
  4. ncbi Myosin-II-dependent localization and dynamics of F-actin during cytokinesis
    Kausalya Murthy
    Department of Biology and Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, 01003, USA
    Curr Biol 15:724-31. 2005
  5. ncbi Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays
    Mark G Manfredi
    Millennium Pharmaceuticals, Inc, Cambridge, 40 Landsdowne Street, Cambridge, MA 02139, USA
    Clin Cancer Res 17:7614-24. 2011
  6. ncbi Drug-resistant aurora A mutants for cellular target validation of the small molecule kinase inhibitors MLN8054 and MLN8237
    Dominic A Sloane
    Yorkshire Cancer Research Institute for Cancer Studies, University of Sheffield, UK
    ACS Chem Biol 5:563-76. 2010
  7. pmc Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice
    Maxime Cazorla
    Neurobiology and Molecular Pharmacology, Centre de psychiatrie et Neurosciences, UMR 894 INSERM Université Paris Descartes, Paris, France
    J Clin Invest 121:1846-57. 2011
  8. ncbi Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase
    Stefan Kubicek
    Research Institute of Molecular Pathology, Vienna Biocenter, Dr Bohrgasse 7, A 1030 Vienna, Austria
    Mol Cell 25:473-81. 2007
  9. ncbi Concentration-dependent modulation of amyloid-beta in vivo and in vitro using the gamma-secretase inhibitor, LY-450139
    Thomas A Lanz
    Pfizer, Inc, Eastern Point Rd, MS 8220 4183, Groton, CT 06340, USA
    J Pharmacol Exp Ther 319:924-33. 2006
  10. pmc Besifloxacin, a novel fluoroquinolone, has broad-spectrum in vitro activity against aerobic and anaerobic bacteria
    Wolfgang Haas
    Bausch and Lomb, Inc, 1400 N Goodman St, Rochester, NY 14609, USA
    Antimicrob Agents Chemother 53:3552-60. 2009

Research Grants

Detail Information

Publications216 found, 100 shown here

  1. pmc Targeting MYC dependence in cancer by inhibiting BET bromodomains
    Jennifer A Mertz
    Constellation Pharmaceuticals, Inc, Cambridge, MA 02142, USA
    Proc Natl Acad Sci U S A 108:16669-74. 2011
    ..These findings demonstrate that pharmacologic inhibition of MYC is achievable through targeting BET bromodomains. Such inhibitors may have clinical utility given the widespread pathogenetic role of MYC in cancer...
  2. pmc Targeting MYCN in neuroblastoma by BET bromodomain inhibition
    Alexandre Puissant
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02215, USA
    Cancer Discov 3:308-23. 2013
    ..BET inhibition conferred a significant survival advantage in 3 in vivo neuroblastoma models, providing a compelling rationale for developing BET bromodomain inhibitors in patients with neuroblastoma...
  3. pmc Small-molecule inhibition of BRDT for male contraception
    Martin M Matzuk
    Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA
    Cell 150:673-84. 2012
    ..These data establish a new contraceptive that can cross the blood:testis boundary and inhibit bromodomain activity during spermatogenesis, providing a lead compound targeting the male germ cell for contraception...
  4. ncbi Myosin-II-dependent localization and dynamics of F-actin during cytokinesis
    Kausalya Murthy
    Department of Biology and Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, 01003, USA
    Curr Biol 15:724-31. 2005
    ..The mechanism(s) that contribute to the spatially and temporally regulated assembly and disassembly of the CR at the cell equator are poorly understood...
  5. ncbi Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays
    Mark G Manfredi
    Millennium Pharmaceuticals, Inc, Cambridge, 40 Landsdowne Street, Cambridge, MA 02139, USA
    Clin Cancer Res 17:7614-24. 2011
    ..Here, we describe preclinical characterization of alisertib (MLN8237), a selective AAK inhibitor, incorporating these novel pharmacodynamic assays...
  6. ncbi Drug-resistant aurora A mutants for cellular target validation of the small molecule kinase inhibitors MLN8054 and MLN8237
    Dominic A Sloane
    Yorkshire Cancer Research Institute for Cancer Studies, University of Sheffield, UK
    ACS Chem Biol 5:563-76. 2010
    ....
  7. pmc Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice
    Maxime Cazorla
    Neurobiology and Molecular Pharmacology, Centre de psychiatrie et Neurosciences, UMR 894 INSERM Université Paris Descartes, Paris, France
    J Clin Invest 121:1846-57. 2011
    ..We further propose that ANA-12 may be a valuable tool for studying BDNF/TrkB signaling and may constitute a lead compound for developing the next generation of therapeutic agents for the treatment of mood disorders...
  8. ncbi Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase
    Stefan Kubicek
    Research Institute of Molecular Pathology, Vienna Biocenter, Dr Bohrgasse 7, A 1030 Vienna, Austria
    Mol Cell 25:473-81. 2007
    ..Our data identify a biologically active HMTase inhibitor that allows for the transient modulation of H3K9me2 marks in mammalian chromatin...
  9. ncbi Concentration-dependent modulation of amyloid-beta in vivo and in vitro using the gamma-secretase inhibitor, LY-450139
    Thomas A Lanz
    Pfizer, Inc, Eastern Point Rd, MS 8220 4183, Groton, CT 06340, USA
    J Pharmacol Exp Ther 319:924-33. 2006
    ..These results suggest that LY-450139 modulates the gamma-secretase complex, eliciting Abeta lowering at high concentrations but Abeta elevation at low concentrations...
  10. pmc Besifloxacin, a novel fluoroquinolone, has broad-spectrum in vitro activity against aerobic and anaerobic bacteria
    Wolfgang Haas
    Bausch and Lomb, Inc, 1400 N Goodman St, Rochester, NY 14609, USA
    Antimicrob Agents Chemother 53:3552-60. 2009
    ..Besifloxacin demonstrated potent, broad-spectrum activity, which was particularly notable against gram-positive and gram-negative isolates that were resistant to other fluoroquinolones and classes of antibacterial agents...
  11. ncbi Oral administration of K-11706 inhibits GATA binding activity, enhances hypoxia-inducible factor 1 binding activity, and restores indicators in an in vivo mouse model of anemia of chronic disease
    Yoko Nakano
    Division of Hematology, Institute of Clinical Medicine, Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki 305 8575, Japan
    Blood 104:4300-7. 2004
    ..These results raise the possibility of using orally administered K-11706 for treating patients with ACD...
  12. ncbi Discovery of the dual orexin receptor antagonist [(7R)-4-(5-chloro-1,3-benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2H-1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the treatment of insomnia
    Christopher D Cox
    Department of Medicinal Chemistry, Merck Research Laboratories, P O Box 4, Sumneytown Pike, West Point, Pennsylvania 19486, USA
    J Med Chem 53:5320-32. 2010
    ....
  13. ncbi Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer's disease
    David B Henley
    Eli Lilly and Company, Lilly Corporate Center, Clinical Research Physician, Alzheimer s Team, DC 6161, Indianapolis, IN 46285 6161, USA
    Expert Opin Pharmacother 10:1657-64. 2009
    ..Therefore, pharmacological agents that reduce A beta formation may be of therapeutic benefit...
  14. pmc Myosin light chain kinase is involved in lipopolysaccharide-induced disruption of colonic epithelial barrier and bacterial translocation in rats
    Raphael Moriez
    Institut National de la Recherche Agronomique, Neuro Gastroenterology and Nutrition Unit, 180 chemin de Tournefeuille, BP 3, 31931 Toulouse Cedex 9, France
    Am J Pathol 167:1071-9. 2005
    ..Inhibition of MLCK-dependent colonocyte cytoskeleton contraction by ML-7 prevents the LPS-induced alterations of CPP and its subsequent effects...
  15. ncbi Unexpected blockade of adipocyte differentiation by K-7174: implication for endoplasmic reticulum stress
    Tsuyoshi Shimada
    Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 409 3898, Japan
    Biochem Biophys Res Commun 363:355-60. 2007
    ..These results indicated a possibility that ER stress suppresses adipocyte differentiation and that GATA inhibitor K-7174 has the potential for interfering with adipogenesis through induction of ER stress...
  16. pmc Initial testing of the aurora kinase A inhibitor MLN8237 by the Pediatric Preclinical Testing Program (PPTP)
    John M Maris
    Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104 4318, USA
    Pediatr Blood Cancer 55:26-34. 2010
    ..MLN8237 is a small molecule inhibitor of Aurora Kinase A (AURKA) that is currently in early phase clinical testing. AURKA plays a pivotal role in centrosome maturation and spindle formation during mitosis...
  17. pmc Ca2+-store-dependent and -independent reversal of Stim1 localization and function
    Jeremy T Smyth
    Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, PO Box 12233, Research Triangle Park, NC 27709, USA
    J Cell Sci 121:762-72. 2008
    ..We conclude that SOCE is tightly coupled to formation of Stim1 puncta, and both SOCE and puncta formation involve a dynamic, reversible signaling complex that probably consists of components in addition to Stim1 and Orai channels...
  18. ncbi Pharmacological properties of GABAA receptors containing gamma1 subunits
    S Khom
    Department of Pharmacology and Toxicology, University of Vienna, Austria
    Mol Pharmacol 69:640-9. 2006
    ..05). These data provide new insight into the pharmacological properties of GABA(A) receptors containing gamma(1) subunits and may aid in the design of specific ligands for this receptor subtype...
  19. ncbi Phagocytosis of apoptotic and necrotic thymocytes is inhibited by PAF-receptor antagonists and affects LPS-induced COX-2 expression in murine macrophages
    Soraya Imon de Oliveira
    Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Av Prof Lineu Prestes, 1730, 05508 900 Sao Paulo, Brazil
    Prostaglandins Other Lipid Mediat 80:62-73. 2006
    ..These findings indicate that apoptotic and necrotic cells share common ligands with PAF and oxLDL and suggest the involvement of PAF-like receptors in the enhanced clearance of these cells...
  20. ncbi Cyclic stretch-induced stress fiber dynamics - dependence on strain rate, Rho-kinase and MLCK
    Chin Fu Lee
    Department of Biomedical Engineering, Texas A and M University, College Station, TX 77843 3120, United States
    Biochem Biophys Res Commun 401:344-9. 2010
    ..These results shed new light on the mechanism by which stress fibers reorient in response to cyclic stretch in different regions of the actin cytoskeleton...
  21. pmc Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL
    Qiang Wen
    Division of Hematology Oncology, Northwestern University, Chicago, IL 60611, USA
    Cell 150:575-89. 2012
    ..Our findings provide a rationale to support clinical trials of MLN8237 and other inducers of polyploidization and differentiation in AMKL...
  22. ncbi Securinine induces p73-dependent apoptosis preferentially in p53-deficient colon cancer cells
    Sonia Rana
    Invenio Therapeutics, Cleveland, Ohio, USA
    FASEB J 24:2126-34. 2010
    ..These studies reveal a novel approach to specifically target colon cancer cells lacking p53 as well as identify a novel clinically relevant pathway to selectively induce p73 in p53-null cells...
  23. pmc A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system
    Randall J Bateman
    Department of Neurology, Washington University School of Medicine, St Louis, MO, USA
    Ann Neurol 66:48-54. 2009
    ..The objective of this study was to determine the effects of a gamma-secretase inhibitor on the production of Abeta in the human CNS...
  24. pmc Growth inhibition and differentiation of human breast cancer cells by the PAFR antagonist WEB-2086
    C Cellai
    Department of Experimental Pathology and Oncology, School of Medicine, University of Florence, Viale G B Morgagni 50, 50134 Florence, Italy
    Br J Cancer 94:1637-42. 2006
    ..Overall, WEB-2086 can be proposed as an effective antiproliferative and differentiative agent with interesting translational opportunities to treat breast cancers in support to conventional chemotherapy...
  25. pmc Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancer
    Takeshi Shimamura
    Authors Affiliations Department of Molecular Pharmacology and Therapeutics, Oncology Research Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois Departments of Medical Oncology and Radiation Oncology Belfer Institute for Applied Cancer Science Ludwig Center at Dana Farber Harvard Cancer Center Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute Department of Medicine, Brigham and Women s Hospital Department of Medicine, Harvard Medical School, Boston, Massachusetts Departament de Fisiologia, Facultat de Farmacia, Universitat de Valencia, Valencia, Spain and Department of Pediatrics, Columbia University Medical Center, New York, New York
    Clin Cancer Res 19:6183-92. 2013
    ....
  26. ncbi WEB-2086 and WEB-2170 trigger apoptosis in both ATRA-sensitive and -resistant promyelocytic leukemia cells and greatly enhance ATRA differentiation potential
    A Laurenzana
    Department of Experimental Pathology and Oncology, University of Florence, Italy
    Leukemia 19:390-5. 2005
    ....
  27. pmc Relative inhibitory potency of molinate and metabolites with aldehyde dehydrogenase 2: implications for the mechanism of enzyme inhibition
    Erin M G Allen
    Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, Iowa 52242, USA
    Chem Res Toxicol 23:1843-50. 2010
    ..It was determined that molinate sulfone is capable of covalently modifying Cys residues, including catalytic Cys302 of ALDH, accounting for the observed enzyme inhibition...
  28. ncbi Efficacy and safety of besifloxacin ophthalmic suspension 0.6% compared with moxifloxacin ophthalmic solution 0.5% for treating bacterial conjunctivitis
    Marguerite B McDonald
    Corneal Specialist and Cataract and Refractive Surgery, Ophthalmic Consultants of Long Island, Lynbrook, NY, USA
    Ophthalmology 116:1615-1623.e1. 2009
    ..To compare the clinical and antimicrobial efficacy of besifloxacin ophthalmic suspension 0.6% with that of moxifloxacin ophthalmic solution 0.5% for the treatment of bacterial conjunctivitis...
  29. pmc Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294
    Yanqi Chang
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA
    Nat Struct Mol Biol 16:312-7. 2009
    ..The inhibitor resembles the bound conformation of histone H3 Lys4 to Arg8, and is positioned in place by residues specific for G9a and GLP through specific interactions...
  30. ncbi Pharmacological characterization of MK-0974 [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide], a potent and orally active calcitonin gene-related pept
    Christopher A Salvatore
    Merck Research Laboratories, WP26A 2000, West Point, PA 19486, USA
    J Pharmacol Exp Ther 324:416-21. 2008
    ..In conclusion, MK-0974 is a highly potent, selective, and orally bioavailable CGRP receptor antagonist, which may be valuable in the acute treatment of migraine...
  31. ncbi Suppression of cytokine response by GATA inhibitor K-7174 via unfolded protein response
    Yosuke Takano
    Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 409 3898, Japan
    Biochem Biophys Res Commun 360:470-5. 2007
    ..These results suggested a novel, UPR-dependent mechanism underlying the anti-inflammatory potential of K-7174...
  32. ncbi JNJ-39220675, a novel selective histamine H3 receptor antagonist, reduces the abuse-related effects of alcohol in rats
    Ruggero Galici
    Bristol Myers Squibb, 5 Research Parkway, Wallingford, CT 06492, USA
    Psychopharmacology (Berl) 214:829-41. 2011
    ..A few recent studies suggest that brain histamine levels and signaling via H(3) receptors play an important role in modulation of alcohol stimulation and reward in rodents...
  33. pmc Self-organized podosomes are dynamic mechanosensors
    Olivier Collin
    Department of Mechanical Science and Engineering, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Curr Biol 18:1288-94. 2008
    ..Our results suggest that podosomes are dynamic mechanosensors in which interactions of myosin tension and actin dynamics are crucial for regulating these self-organized structures in living cells...
  34. ncbi Specific PAF antagonist WEB-2086 induces terminal differentiation of murine and human leukemia cells
    Cristina Cellai
    Department of Experimental Pathology and Oncology, University of Florence, 50134, Firenze, Italy
    FASEB J 16:733-5. 2002
    ....
  35. ncbi Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine
    T W Ho
    Merck Research Laboratories, UG 4C 18, PO Box 1000, North Wales, PA 19454 1099, USA
    Neurology 70:1304-12. 2008
    ..To determine an effective and tolerable dose of a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, for the acute treatment of migraine...
  36. ncbi Ocular pharmacokinetics of besifloxacin following topical administration to rabbits, monkeys, and humans
    Joel W Proksch
    Global Research and Development, Bausch and Lomb, 1400 N Goodman Street, Rochester, NY 14609, USA
    J Ocul Pharmacol Ther 25:335-44. 2009
    ..Studies were conducted to evaluate the ocular penetration and systemic exposure to besifloxacin, a fluoroquinolone antibiotic, following topical ocular administration to animals and humans...
  37. pmc Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system
    Andrea Stephanie Link
    Biomedical Center Lund, Lund, Sweden
    J Headache Pain 9:5-12. 2008
    ..The purpose of this review is to give a short overview of the pathological background of migraine headache and to illustrate the mechanisms behind the actions of triptans and the promising CGRP receptor blockers...
  38. ncbi Excellent tolerability but relatively low initial clinical efficacy of telcagepant in migraine
    Peer Tfelt-Hansen
    Danish Headache Centre, Department of Neurology, University of Copenhagen, Glostrup Hospital, Glostrup, Denmark
    Headache 51:118-23. 2011
    ..The introduction of calcitonin gene-related peptide receptor antagonism in the acute treatment of migraine is a major step forward but so far mostly because of its specific mode of action and excellent tolerability...
  39. pmc Randomized, controlled trial of telcagepant for the acute treatment of migraine
    K M Connor
    Merck Research Laboratories, North Wales, PA 19454 1099, USA
    Neurology 73:970-7. 2009
    ..In this large phase 3 clinical trial, we sought to confirm the efficacy of telcagepant, the first orally bioavailable CGRP receptor antagonist...
  40. ncbi Securinine, a GABAA receptor antagonist, enhances macrophage clearance of phase II C. burnetii: comparison with TLR agonists
    Kirk Lubick
    Veterinary Molecular Biology, Montana State University, Bozeman, MT 59718, USA
    J Leukoc Biol 82:1062-9. 2007
    ..Securinine has minimal toxicity in vivo, suggesting it or structurally similar compounds may represent novel, therapeutic adjuvants, which increase resistance to intracellular pathogens...
  41. ncbi Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial
    Tony W Ho
    Merck Research Laboratories, North Wales, PA 19454 1099, USA
    Lancet 372:2115-23. 2008
    ..We aimed to assess the clinical profile of MK-0974 (telcagepant), an orally bioavailable antagonist of CGRP receptor...
  42. ncbi Myosin light-chain kinase contributes to short-term endothelial cell cytoskeletal alteration induced by serum from burned rats
    Bo Chen
    Department of Pathophysiology, First Military Medical University, Guangzhou 510515, China
    Di Yi Jun Yi Da Xue Xue Bao 24:481-4, 488. 2004
    ....
  43. ncbi Phase III efficacy and safety study of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis
    Michael E Tepedino
    Cornerstone Eye Care, High Point, NC, USA
    Curr Med Res Opin 25:1159-69. 2009
    ..To compare the clinical and antimicrobial efficacy of besifloxacin ophthalmic suspension 0.6% with that of vehicle in the treatment of bacterial conjunctivitis...
  44. ncbi Besifloxacin ophthalmic suspension 0.6% in patients with bacterial conjunctivitis: A multicenter, prospective, randomized, double-masked, vehicle-controlled, 5-day efficacy and safety study
    Paul Karpecki
    Koffler Vision Group, Lexington, Kentucky 40509, USA
    Clin Ther 31:514-26. 2009
    ..6% is a new topical fluoroquinolone for the treatment of bacterial conjunctivitis. Besifloxacin has potent in vitro activity against a broad spectrum of ocular pathogens, including drug-resistant strains...
  45. ncbi Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli
    Emmanuelle Cambau
    Université Paris12, Creteil, France
    J Antimicrob Chemother 63:443-50. 2009
    ..We investigated its mode of action and resistance in two major ocular pathogens, Streptococcus pneumoniae and Staphylococcus aureus, and in the reference species Escherichia coli...
  46. ncbi Nonclinical pharmacodynamics, pharmacokinetics, and safety of BOL-303224-A, a novel fluoroquinolone antimicrobial agent for topical ophthalmic use
    Keith W Ward
    Global Preclinical Development, Bausch and Lomb, Rochester, NY 14603, USA
    J Ocul Pharmacol Ther 23:243-56. 2007
    ..In summary, BOL-303224-A exhibits an encouraging nonclinical pharmacodynamic, pharmacokinetic, and safety profile that supports clinical development as a topical agent for the potential treatment of ophthalmic infections...
  47. ncbi Structure of human cytidine deaminase bound to a potent inhibitor
    Sang J Chung
    Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA
    J Med Chem 48:658-60. 2005
    ..The structure reveals that inhibitor 1 is able to establish a canonical pi/pi-interaction with a key active site residue, Phe 137...
  48. ncbi Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer disease
    E R Siemers
    Eli Lilly and Company, Indianapolis, IN 46085, USA
    Neurology 66:602-4. 2006
    ..Abeta(1-40) in plasma decreased by 38.2%; in CSF, Abeta(1-40) decreased by 4.42 +/- 9.55% (p = not significant). Higher drug doses may result in additional decreases in plasma Abeta concentrations and a measurable decrease in CSF Abeta...
  49. pmc Growth cone collapse through coincident loss of actin bundles and leading edge actin without actin depolymerization
    F Q Zhou
    Department of Anatomy and Cell Biology, State University of New York at Buffalo, Buffalo, NY 14214, USA
    J Cell Biol 153:1071-84. 2001
    ..Taken together, these results suggest that actin bundles could be a common cytoskeletal target of various collapsing factors, which may use different signaling pathways that converge to induce growth cone collapse...
  50. ncbi Potent inhibitors for the deamination of cytosine arabinoside and 5-aza-2'-deoxycytidine by human cytidine deaminase
    J Laliberte
    Departement de Pharmacologie, Universite de Montreal, Quebec, Canada
    Cancer Chemother Pharmacol 30:7-11. 1992
    ..The inhibition constants for diazepinone riboside lay in the range of 5-15 nM, suggesting that this inhibitor could be an excellent candidate for use in combination chemotherapy with either ARA-C or 5-AZA-CdR in patients with leukemia...
  51. ncbi Selective inhibition of catalytic activity of smooth muscle myosin light chain kinase
    M Saitoh
    J Biol Chem 262:7796-801. 1987
    ..The potent vaso-relaxing effect of ML-9 on rabbit vascular strips and on saponin-treated skinned smooth muscle cells was discussed in relation to the in vivo inhibition by this drug of smooth muscle myosin light chain kinase...
  52. ncbi Pre-clinical characterization of aryloxypyridine amides as histamine H3 receptor antagonists: identification of candidates for clinical development
    Michael A Letavic
    Johnson and Johnson Pharmaceutical Research and Development L L C, 3210 Merryfield Row, San Diego, CA 92121, USA
    Bioorg Med Chem Lett 20:4210-4. 2010
    ..Several compounds were extensively profiled pre-clinically leading to the identification of two compounds suitable for nomination as development candidates...
  53. ncbi Bengamides revisited: new structures and antitumor studies
    Z Thale
    Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA
    J Org Chem 66:1733-41. 2001
    ..The best activity was observed for the natural bengamides A (IC(50) = 1 nM) and O (IC(50) = 0.3 nM)...
  54. ncbi Safety, tolerability, and changes in amyloid beta concentrations after administration of a gamma-secretase inhibitor in volunteers
    Eric Siemers
    Lilly Research Laboratories, Indianapolis, Indiana 46285, USA
    Clin Neuropharmacol 28:126-32. 2005
    ..A dose-dependent reduction in plasma Abeta was demonstrated, and changes in plasma Abeta concentrations were temporally related to the pharmacokinetic characteristics of LY450139...
  55. ncbi Mechanistic insight into WEB-2170-induced apoptosis in human acute myelogenous leukemia cells: the crucial role of PTEN
    Cristina Cellai
    Department of Experimental Pathology and Oncology, University of Florence, 50134 Florence, Italy
    Exp Hematol 37:1176-1185.e21. 2009
    ..This study aimed to investigate the mechanisms of action of WEB-2170, an inverse agonist of platelet-activating factor receptor, capable of inducing apoptosis in human acute myelogenous leukemia (AML) cells...
  56. ncbi PAF antagonist treatment reduces pro-inflammatory cytokine mRNA after spinal cord injury
    Mary Ellen Hostettler
    Department of Anatomy and Neurobiology, University of Kentucky Medical Center, Lexington 40536, USA
    Neuroreport 13:21-4. 2002
    ..p.) 15 min prior to injury significantly decreased mRNA levels for all three cytokines at 6 h post-injury, but not at I h post-injury. These results demonstrate a role for PAF in proinflammatory cytokine induction after SCI...
  57. ncbi Effects of anti-myosin drugs on anaphase chromosome movement and cytokinesis in crane-fly primary spermatocytes
    R V Silverman-Gavrila
    Biology Department, York University, Toronto, Ontario, Canada
    Cell Motil Cytoskeleton 50:180-97. 2001
    ..H-7 had no effect. These results confirm that the effects of BDM are on myosin and indicate that the myosin used for cytokinesis is activated starting from autosomal anaphase and continuing throughout cytokinesis...
  58. ncbi Myosin light chain kinase inhibitors induce retraction of mature oligodendrocyte processes
    María G Thomas
    IIB Fundación Campomar, IIB FCEyN, University of Buenos Aires and IIBBA CONICET, Buenos Aires, Argentina
    Neurochem Res 27:1305-12. 2002
    ..Our results suggest that the adhesion of the myelinating processes to the substrate depends on MLC phosphorylation, thus likely implicating myosin IIA...
  59. ncbi Potent, orally bioavailable calcitonin gene-related peptide receptor antagonists for the treatment of migraine: discovery of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1- (2,2,2-trifluoroethyl)azepan-3-yl]-4- (2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin- 1-yl
    Daniel V Paone
    Department of Medicinal Chemistry, Merck Research Laboratories, P O Box 4, West Point, Pennsylvania 19486, USA
    J Med Chem 50:5564-7. 2007
    ....
  60. pmc A multigram chemical synthesis of the gamma-secretase inhibitor LY411575 and its diastereoisomers
    Abdul H Fauq
    Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Bioorg Med Chem Lett 17:6392-5. 2007
    ..Starting from the resolved aminolactams 5a and 5b, all four diastereomers were produced in enantiomerically pure form...
  61. ncbi Studies of Abeta pharmacodynamics in the brain, cerebrospinal fluid, and plasma in young (plaque-free) Tg2576 mice using the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]az
    Thomas A Lanz
    Pfizer Inc, Eastern Point Road, MS 8220 4183, Groton, CT 06340, USA
    J Pharmacol Exp Ther 309:49-55. 2004
    ..Overall, Abeta in the CSF and not plasma seems to be a better biomarker of brain Abeta reduction; however, the time course of Abeta changes needs to be established in clinical studies...
  62. ncbi Redundant mechanisms for anaphase chromosome movements: crane-fly spermatocyte spindles normally use actin filaments but also can function without them
    Lacramioara Fabian
    Biology Department, York University, Toronto, Ontario, Canada
    Protoplasma 225:169-84. 2005
    ....
  63. ncbi Studies to investigate the in vivo therapeutic window of the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY411,575) in the CRND8 mouse
    Lynn A Hyde
    Department of Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    J Pharmacol Exp Ther 319:1133-43. 2006
    ....
  64. ncbi Platelet-activating factor stimulates ovine foetal pulmonary vascular smooth muscle cell proliferation: role of nuclear factor-kappa B and cyclin-dependent kinases
    B O Ibe
    Division of Neonatology, Harbor UCLA Medical Center, Los Angeles Biomedical Institute, Harbor UCLA Medical Center, 1124 West Carson Street, Torrance, CA 90502, USA
    Cell Prolif 41:208-29. 2008
    ..We investigated involvement of PAF and PAF receptors in PVSMC proliferation...
  65. ncbi Laminin-311 (Laminin-6) fiber assembly by type I-like alveolar cells
    Phillip J DeBiase
    Division of Pulmonary Medicine, Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Tarry 8 715, 303 E Chicago Avenue, Chicago, IL 60611, USA
    J Histochem Cytochem 54:665-72. 2006
    ..In summary, our data indicate that assembly of laminin-311 fibers by lung epithelial cells is integrin and actin cytoskeleton dependent, and that these fibers are characteristic of type I alveolar cells...
  66. ncbi Implication of phosphorylation of the myosin II regulatory light chain in insulin-stimulated GLUT4 translocation in 3T3-F442A adipocytes
    Young Ok Choi
    Department of Physiology, University of Ulsan College of Medicine, Seoul 138 736, Korea
    Exp Mol Med 38:180-9. 2006
    ..Our studies suggest that MLCK may be a regulatory target of Ca(2+)/calmodulin and may play an important role in insulin-stimulated glucose transport in adipocytes...
  67. ncbi An MLCK-dependent window in late G1 controls S phase entry of proliferating rodent hepatocytes via ERK-p70S6K pathway
    Anne Bessard
    INSERM U522, Unité de Recherches Hépatologiques IFR 140 Université de Rennes1, Rennes, France
    Hepatology 44:152-63. 2006
    ....
  68. ncbi Inhibiting myosin light chain kinase retards the growth of mammary and prostate cancer cells
    Lian Zhi Gu
    Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, 835 South Wolcott Ave, Chicago, IL 60612 7342, USA
    Eur J Cancer 42:948-57. 2006
    ..These results provide evidence for the efficacy of ML-7 as an adjuvant to etoposide in these models and warrants further development...
  69. ncbi Myosin light chain kinase regulates synaptic plasticity and fear learning in the lateral amygdala
    R Lamprecht
    W M Keck Foundation Laboratory for Neurobiology, Center for Neural Science, New York University, 4 Washington Place, Room 809, New York, NY 10003, USA
    Neuroscience 139:821-9. 2006
    ..Impairment of this mechanism could contribute to pathological fear learning...
  70. ncbi 9-cyano-1-azapaullone (cazpaullone), a glycogen synthase kinase-3 (GSK-3) inhibitor activating pancreatic beta cell protection and replication
    Hendrik Stukenbrock
    Institut fur Pharmazeutische Chemie, Technische Universitat Braunschweig, Beethovenstrasse 55, Braunschweig, Germany
    J Med Chem 51:2196-207. 2008
    ..These features distinguish cazpaullone as a unique starting point for the development of beta cell regenerative agents which might be useful in the treatment of diabetes...
  71. ncbi Inhibition of the myosin light chain kinase prevents hypoxia-induced blood-brain barrier disruption
    Christoph R W Kuhlmann
    Institute of Physiology and Pathophysiology, Johannes Gutenberg University of Mainz, Mainz, Germany
    J Neurochem 102:501-7. 2007
    ..Furthermore, ML-7 and apocynin blocked hypoxia-dependent phosphorylation of MLC. Our data demonstrate that hypoxia causes a breakdown of the BBB in vitro and in vivo involving ROS and the contractile machinery...
  72. pmc Dual role for myosin II in GLUT4-mediated glucose uptake in 3T3-L1 adipocytes
    F Kent Fulcher
    Department of Biology, University of North Carolina at Greensboro, Greensboro, North Carolina 27402, USA
    Exp Cell Res 314:3264-74. 2008
    ..Collectively, our results are the first to reveal that myosin IIA plays a critical role in mediating insulin-stimulated glucose uptake in 3T3-LI adipocytes, via both GLUT4 vesicle fusion at the plasma membrane and GLUT4 activity...
  73. ncbi [Effect of actomyosin contractility on focal contacts of myofibroblasts and structure of stress fibers]
    V B Dugina
    A N Belozersky Institute of Physico Chemical Biology, Moscow State University, Russia
    Tsitologiia 44:48-55. 2002
    ..Thus, actin-myosin contractility controls the structure of "supermature" focal contacts of myofibroblasts and alpha-SMA expression in stress fibers...
  74. ncbi Theoretical and experimental investigation of calcium-contraction coupling in airway smooth muscle
    Prisca Mbikou
    Universite Bordeaux 2, Laboratoire de Physiologie Cellulaire Respiratoire, Bordeaux, F 33076 France Inserm, E356, Bordeaux, F 33076 France
    Cell Biochem Biophys 46:233-52. 2006
    ..The long-time phase of the contraction, associated with a second increase in MLC phosphorylation, may be explained, at least partially, by MLC phosphatase (MLCP) inhibition, possibly via PKC inhibition...
  75. pmc Phospholipase C and myosin light chain kinase inhibition define a common step in actin regulation during cytokinesis
    Raymond Wong
    Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, TMDT Building, East Tower, Toronto, Ontario, Canada
    BMC Cell Biol 8:15. 2007
    ..However, the specificity of U73122 is unclear, as its active group closely resembles the non-specific alkylating agent N-ethylmaleimide (NEM). In addition, the pathway by which PIP2 regulates cytokinesis remains to be elucidated...
  76. ncbi The participation of the Na+-Ca2+ exchanger in primary cardiac myofibroblast migration, contraction, and proliferation
    Joshua E Raizman
    Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre and Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada
    J Cell Physiol 213:540-51. 2007
    ..NCX1 may represent an important moiety in suppression of myofibroblast functions...
  77. ncbi Organized migration of epithelial cells requires control of adhesion and protrusion through Rho kinase effectors
    Ann M Hopkins
    Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, USA
    Am J Physiol Gastrointest Liver Physiol 292:G806-17. 2007
    ....
  78. ncbi Cellular mechanisms of mainstream cigarette smoke-induced lung epithelial tight junction permeability changes in vitro
    Dorian S Olivera
    Program in Toxicology, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
    Inhal Toxicol 19:13-22. 2007
    ..Additionally, our results indicate that activation of PTK and ROCK and inactivation of MLCK contribute to the increased airway permeability caused by mainstream cigarette smoke...
  79. ncbi Interaction of non-adherent suspended neutrophils to complement opsonized pathogens: a new assay using optical traps
    Tomoko Suzuki
    Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai 980 8574, Japan
    Cell Res 16:887-94. 2006
    ....
  80. ncbi In vivo phosphorylation of regulatory light chain of myosin II in sea urchin eggs and its role in controlling myosin localization and function during cytokinesis
    Ryota Uehara
    Department of Biology, School of Arts and Sciences, University of Tokyo, 3 8 1 Komaba, Tokyo 153 8902, Japan
    Cell Motil Cytoskeleton 65:100-15. 2008
    ..These results suggested that RLC mono-phosphorylation by more than two RLC kinases play a main role in regulation and localization of myosin in the dividing sea urchin eggs...
  81. pmc Calcium absorption by Cav1.3 induces terminal web myosin II phosphorylation and apical GLUT2 insertion in rat intestine
    Oliver J Mace
    Department of Biology, The University of York, York YO10 5YW, UK
    J Physiol 580:605-16. 2007
    ....
  82. ncbi Role of platelet-activating factor in phosphatidylcholine secretion in primary cultures of rat type II pneumocytes
    E Benito
    Department of Biochemistry and Molecular Biology, Faculty of Chemistry, Universidad Complutense, Madrid, Spain
    Prostaglandins Other Lipid Mediat 67:197-208. 2002
    ..This involvement was further supported by the use of inhibitors of protein kinases and by the stimulation of cAMP production in type II pneumocytes incubated with PAF...
  83. ncbi Proteinase-activated receptor-2-induced colonic inflammation in mice: possible involvement of afferent neurons, nitric oxide, and paracellular permeability
    Nicolas Cenac
    Neuro Gastroenterology and Nutrition Unit, Institut National de la Recherche Agronomique, Toulouse, France
    J Immunol 170:4296-300. 2003
    ..Nevertheless, the inflammation process is not a consequence of increased permeability which results at least in part from the activation of myosin L chain kinase...
  84. ncbi Myofibrillogenesis in the first cardiomyocytes formed from isolated quail precardiac mesoderm
    Aiping Du
    Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6058, USA
    Dev Biol 257:382-94. 2003
    ....
  85. ncbi Functional diversity between Rho-kinase- and MLCK-mediated cytoskeletal actions in a myofibroblast-like hepatic stellate cell line
    Mikio Yanase
    Department of Gastroenterology, Faculty of Medicine, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, 113 0033, Tokyo, Japan
    Biochem Biophys Res Commun 305:223-8. 2003
    ..These findings suggest that the actomyosin-based cytoskeletal actions can be functionally diverse depending on the Rho-kinase-mediated pathway and the MLCK-mediated pathway...
  86. ncbi Preventive effect of platelet-activating factor antagonist, Y-24180, against cyclosporine-induced acute nephrotoxicity
    A Kawaguchi
    Department of Clinical Pharmacology, Jichi Medical School, Kawachi-gun, Tochigi, Japan
    Life Sci 68:1181-90. 2001
    ..The present findings also support the idea that Et contributes to the CsA-induced acute nephrotoxicity...
  87. ncbi ML-7 inhibits exocytosis of superoxide-producing intracellular compartments in human neutrophils stimulated with phorbol myristate acetate in a myosin light chain kinase-independent manner
    Keita Odani
    Department of Radiology, Kochi Medical School, Nankoku, 783 5305 Kochi, Japan
    Histochem Cell Biol 119:363-70. 2003
    ....
  88. ncbi Parallel liquid synthesis of N,N'-Disubstituted 3-amino azepin-2-ones as potent and specific farnesyl transferase inhibitors
    Thierry Le Diguarher
    Department of Medicinal Chemistry, Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy sur Seine, France
    Bioorg Med Chem 11:3193-204. 2003
    ..The activities of the selected compounds were validated in vivo, and compounds 41a and 44a presented significant antitumour activity...
  89. ncbi Dependence of metastatic cancer cell invasion on MLCK-catalyzed phosphorylation of myosin regulatory light chain
    R Tohtong
    Department of Biochemistry, Faculty of Science, Mahidol University, Phya Thai, Bangkok, Thailand
    Prostate Cancer Prostatic Dis 6:212-6. 2003
    ....
  90. ncbi Degranulation in RBL-2H3 cells: regulation by calmodulin pathway
    Masayuki Funaba
    Laboratory of Nutrition, Azabu University School of Veterinary Medicine, 1 17 71 Fuchinobe, Sagamihara 229 8501, Japan
    Cell Biol Int 27:879-85. 2003
    ....
  91. ncbi Role of the actin cytoskeleton in regulating endothelial permeability in venules
    J Edward Valeski
    Department of Physiology, College of Medicine, University of Arizona, Tucson, AZ 85724 5051, USA
    Microcirculation 10:411-20. 2003
    ..This study was performed to determine the effect of myosin light chain kinase (MLCK) inhibition on histamine- and thrombin-induced venular permeability in the rat mesentery, coincidental with actin cytoskeleton changes...
  92. ncbi Synthesis of N,N'-disubstituted 3-aminobenzo[c] and [d]azepin-2-ones as potent and specific farnesyl transferase inhibitors
    Thierry Le Diguarher
    Department of Medicinal Chemistry, Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy sur Seine, France
    Bioorg Med Chem Lett 14:767-71. 2004
    ..A structure-activity study was performed by synthesis on N,N'-disubstitution of 3-aminobenzo[c] and [d]azepin-2-one 2 and 3 to afford potent and specific farnesyl transferase inhibitors with low nM enzymatic and cellular activities...
  93. ncbi Rapid actin transport during cell protrusion
    Daniel Zicha
    Light Microscopy, Cancer Research UK, Lincoln s Inn Fields Laboratories, London WC2A 3PX, UK
    Science 300:142-5. 2003
    ..Monte Carlo modeling confirmed that this flow cannot be explained by diffusion and may involve active transport...
  94. ncbi Inhibition of contractile activation reduces reoxygenation-induced endothelial gap formation
    C Schafer
    Institute of Physiology, Justus Liebig University Giessen, Germany
    Cardiovasc Res 58:149-55. 2003
    ..4) and reperfusion (30 min reoxygenation, pH(o) 7.4)...
  95. ncbi PAF- and bradykinin-induced hyperpermeability of rat venules is independent of actin-myosin contraction
    R H Adamson
    Departmentof Human Physiology, School of Medicine, University of California Davis, Davis, CA 95616, USA
    Am J Physiol Heart Circ Physiol 285:H406-17. 2003
    ..The results are consistent with paracellular gap formation by local release of endothelial-endothelial cell adhesion structures in the absence of contraction by the actin-myosin network...
  96. ncbi Cyclic AMP-dependent protein kinase A plays a role in the directed migration of human keratinocytes in a DC electric field
    C E Pullar
    Department of Dermatology, University of California, Davis, CA 95616, USA
    Cell Motil Cytoskeleton 50:207-17. 2001
    ..The inhibitor studies described in this paper implicate a role for PKA in the regulation of the directional migratory response to applied electric fields, galvanotaxis...
  97. ncbi Participation of prostaglandin E2 and platelet-activating factor in thapsigargin-induced production of interleukin-6
    Gaku Ichinowatari
    Laboratory of Pathophysiological Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba ku, Sendai, Miyagi 980 8578, Japan
    Eur J Pharmacol 434:187-96. 2002
    ..These findings suggested that the concurrently produced prostaglandin E2 and intracellular PAF participate in the thapsigargin-induced increase in the interleukin-6 mRNA level and interleukin-6 production by rat peritoneal macrophages...
  98. ncbi Myosin light chain phosphorylation in neutrophil-stimulated coronary microvascular leakage
    Sarah Y Yuan
    Departments of Surgery and Medical Physiology, Cardiovascular Research Institute, Texas A and M University Health Science Center, Temple, Texas, USA yuan tamu edu
    Circ Res 90:1214-21. 2002
    ..Taken together, the results suggest that endothelial MLCK activation and MLC phosphorylation play an important role in mediating endothelial barrier dysfunction during neutrophil activation...
  99. ncbi Myosin light chain kinase inhibitors can block invasion and adhesion of human pancreatic cancer cell lines
    Kenzo Kaneko
    Department of Gastroenterology, Division of Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyaga, Japan
    Pancreas 24:34-41. 2002
    ..A cytoskeletal component indispensable for these processes is myosin II, the cytoplasmic analogue of smooth and skeletal muscle myosin...
  100. ncbi The renal effects of Bothrops jararacussu venom and the role of PLA(2) and PAF blockers
    A Havt
    Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo 1127, 60430-270 Fortaleza, CE, Brazil
    Toxicon 39:1841-6. 2001
    ..Dexamethasone did not block the renal effects maybe because of the concentration used in this work or maybe the renal effects are promoted by the myotoxin, which does not have PLA(2) activity...
  101. ncbi Platelet-activating factor antagonists decrease the inflammatory nociceptive response in rats
    Lisa A Teather
    Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 45 Carleton Street, E25 604, Cambridge, MA 02139, USA
    Psychopharmacology (Berl) 163:430-3. 2002
    ..Evidence suggests that PAF exerts cellular actions through a plasma membrane receptor as well as via intracellular (microsomal) PAF binding sites...

Research Grants58

  1. N-Heterocycles from Azides through Rhodium-Catalyzed Nitrenoid Transfer
    TOM GREGORY DRIVER; Fiscal Year: 2012
    ..or o-anthranil decomposition to enable the rapid synthesis of heteroaromatic carbazoles, indoles, functionalized azepines, and aziridines...
  2. ROUTES TO CHIRAL CARBOCYCLIC AND HETEROCYCLIC COMPOUNDS
    A Meyers; Fiscal Year: 2000
    ..chemistry which will access a number of important classes of chiral heterocycles (piperidines, pyrrolidines, azepines) as well as multifunctional carbocycles whose architecture quickly suggest they can be used to reach a variety of ..
  3. Neuropsychopharmacol Interactions - Cocaine & Serotonin
    KATHRYN CUNNINGHAM; Fiscal Year: 2004
    ..Thus, the release time and salary support provided by this K02 would continue to enhance the development of my career in the science of drug dependence. ..
  4. Targeted Proteomics of Stress and Addiction
    KATHRYN CUNNINGHAM; Fiscal Year: 2005
    ..abstract_text> ..
  5. NEUROBEHAVIORAL PHARMACOLOGY OF STIMULANTS
    Kathryn A Cunningham; Fiscal Year: 2010
    ....
  6. NEUROPSYCHOPHARMACOLOGY MDMA--MONOAMINERGIC MECHANISMS
    KATHRYN CUNNINGHAM; Fiscal Year: 2005
    ..abstract_text> ..
  7. INTERESTING BIOACTIVE SUBSTANCES
    David Williams; Fiscal Year: 2006
    ..The selective synthesis of contiguous stereotriads will advance basic methodology for asymmetric conjugate additions. ..
  8. CHEMICAL SYNTHESIS OF NOVEL NATURAL PRODUCTS
    David Williams; Fiscal Year: 2009
    ..Daphnicyclidin A. This recent discovery has revealed a new molecular architecture which exhibits significant antitumor activity. Our research will investigate strategies for chemical synthesis of these complex polycyclic systems. ..
  9. Micropallet Arrays for Separation of Single Cells and Colonies
    Nancy L Allbritton; Fiscal Year: 2010
    ..The applications which involve basic cell biology, tumorigenesis, and signaling mechanisms in diabetes mellitus will demonstrate that the novel separation system should be widely applicable to the biomedical sciences. ..
  10. Computer-aided Design of Anti-cancer Drugs Targeting Protein Kinases
    Chung Wong; Fiscal Year: 2006
    ..Specific Aim 5 applies this refined five-tier hierarchical model to identify new anti-cancer drug candidates for the protein kinase targets EGFR, HER2, CDK2, and BCR-ABL. [unreadable] [unreadable] [unreadable]..
  11. Significance of Genetic Alterations in Neuroblastoma
    John Maris; Fiscal Year: 2006
    ..It is expected that these will be of prognostic importance and serve as specific targets for developmental therapeutics. ..
  12. Tandem Cycloaddition Chemistry of 2-Azoniaheterodienes
    SCOTT DENMARK; Fiscal Year: 2007
    ..abstract_text> ..
  13. An Automated Platform for Kinase Assays on Patient Cells
    Nancy Allbritton; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  14. Mechanistic Studies of Anti-HIV Activity of a Novel Ring-Expanded Nucleoside
    RAMACHANDRA HOSMANE; Fiscal Year: 2007
    ..Finally, we will investigate if the leading REN as well as its analogues are effective against the resistant HIV mutants. [unreadable] [unreadable] [unreadable]..
  15. METHODOLOGY FOR THE SYNTHESIS OF NITROGEN HETEROCYCLES
    Philip Magnus; Fiscal Year: 2007
    ..The synthetic intermediates, particularly as they more closely resemble the natural products, will be screened to assess biological activity. [unreadable] [unreadable]..
  16. Phase I Radiosensitization Study of GW572016 in Recurrent Breast Cancer
    ELIZABETH DEES; Fiscal Year: 2007
    ..This proposal pilots a novel combination therapy to treat this common and challenging clinical problem. [unreadable] [unreadable] [unreadable]..
  17. CGRP Regulation of iNOS and MAP Kinases/Phosphatases in Trigeminal Ganglia Glia
    Paul L Durham; Fiscal Year: 2010
    ....
  18. Enteropathogenic E. coli Effects on Intestinal Function
    Gail A Hecht; Fiscal Year: 2010
    ..4. To evaluate the effect of EPEC infection on TJ structure and function in vivo using a mouse model and investigate the effector molecules and mechanisms involved. ..
  19. HYPONATREMIA-INDUCED OSTEOPOROSIS
    Joseph G Verbalis; Fiscal Year: 2010
    ....
  20. Cross-Coupling Reactions of Organosilanols
    SCOTT DENMARK; Fiscal Year: 2009
    ..Synthetic approaches to isodomoic acid H, hepatitis C viral inihibiting indole alkaloids, the salicylihalimide macrolactone oximidine II, and polyene antiviral antibiotic viridenomycin are detailed. ..
  21. Control of Genomic Stability by Emi1 and Securin
    NORMAN LEHMAN; Fiscal Year: 2007
    ..abstract_text> ..
  22. Anti-plague agents targeting YopH of Yersinia Pestis
    Chung Wong; Fiscal Year: 2008
    ..It is the pathogen that causes plague and can be misused as a weapon. This research aims at identifying anti-plague agents that target a protein called YopH of this bacterium. [unreadable] [unreadable] [unreadable]..
  23. CATCH: Mechanochemistry and Regulation in Smooth Muscle
    Thomas Butler; Fiscal Year: 2008
    ..4) Determination of the extent of involvement of myosin crossbridges in catch force maintenance by measurements of changes in orientation of fluorescent probes attached to the regulatory light chain. ..
  24. BOLD and Perfusion fMRI of Alzheimer's Disease Risk
    Adam Fleisher; Fiscal Year: 2008
    ....
  25. Structural Biology of Cardiovascular Signaling
    Avril Somlyo; Fiscal Year: 2008
    ..abstract_text> ..
  26. Rapid Analysis of Signaling in Adherent Cells
    Nancy Allbritton; Fiscal Year: 2008
    ....
  27. CGRP CONTROL IN TRIGEMINAL NEURONS IN VITRO AND IN VIVO
    Paul Durham; Fiscal Year: 2006
    ..abstract_text> ..
  28. P450 PHENOTYPE AND CHEMOTHERAPY TOXICITY IN THE ELDERLY
    ELIZABETH DEES; Fiscal Year: 2006
    ..They have assembled a carefully selected group of collaborators and advisors to assist in the research projects and Dr. Dees's career development. ..
  29. BRAIN OXYTOCIN AND ETHANOL EFFECT ON INGESTIVE BEHAVIOR
    Joseph Verbalis; Fiscal Year: 2001
    ....
  30. Profiling Ras Activated Signal Transduction Pathways
    Nancy Allbritton; Fiscal Year: 2004
    ..The successful completion of this work will provide a new and powerful tool for basic research, drug discovery and screening, cancer classification, and potentially clinical decision making. ..
  31. LIPOPHILIC ANTIFOLATES AND AIDS OPPORTUNISTIC INFECTIONS
    Andre Rosowsky; Fiscal Year: 2004
    ..Analogs of PT653 with a COOH, NH2, or OH group on the tricyclic moiety, and prodrugs thereof, will be made with the goal of improving aqueous solubility without sacrificing potency or selectivity. ..
  32. SYNTHESIS OF DIAZONAMIDES
    Philip Magnus; Fiscal Year: 2004
    ..Part of the synthetic studies will involve the generation of persistent radical intermediates that should add to pi-deficient heterocycles and form the key central hindered bond present in the diazonamides. ..
  33. SIGNAL TRANSDUCTION THROUGH CALCIUM WAVES
    Nancy Allbritton; Fiscal Year: 2003
    ....
  34. NOVEL APPROACHES TO ANTIFOLATE CHEMOTHERAPY
    Andre Rosowsky; Fiscal Year: 2003
    ..The focus will be on enhancing polyglutamation of the lead compound dmAMT by modification of the B-ring and/or pABA moiety. ..
  35. DISSECTING ENZYMATIC NETWORKS IN SINGLE NEURONS
    Nancy Allbritton; Fiscal Year: 2003
    ..This information can be used to map the temporal interrelationships of neuronal signaling networks. As a result many fundamental questions regarding neuronal development, synaptic plasticity, brain injury, and aging can be answered. ..
  36. PHYSIOLOGICAL ADAPTATION TO SUSTAINED HYPO-OSMOLALITY
    Joseph Verbalis; Fiscal Year: 2002
    ..These studies should lead to an elucidation of the cellular mechanisms underlying one of the most basic and intriguing unanswered question about clinically hyponatremic disorders. ..
  37. NOVEL ORGANIC REAGENTS FOR BIOMEDICAL APPLICATIONS
    RAMACHANDRA HOSMANE; Fiscal Year: 2002
    ..abstract_text> ..
  38. Nitric Oxide Control of CGRP in Trigeminal Neurons
    Paul Durham; Fiscal Year: 2002
    ..abstract_text> ..
  39. SYNTHESIS OF NOVEL BIOLOGICALLY ACTIVE NATURAL PRODUCTS
    ROBERT BOECKMAN; Fiscal Year: 2002
    ..The hypothesis that an internal chelate of suitably disposed oxygen functions permits the modification of the ring conformation from half-chair to half-boat will be tested. ..
  40. MEASUREMENT OF KINASE ACTIVITIES IN SINGLE TUMOR CELLS
    Nancy Allbritton; Fiscal Year: 2001
    ..When fully developed, this integrated microchip will represent a new paradigm in single-cell measurement techniques. ..
  41. Anti-Inflammatory PAF Acetylhydrolase in Lung Injury
    Katherine Howard; Fiscal Year: 2004
    ..Through the logical design of the proposed studies, novel and important information will be gained that will significantly advance our understanding of the cell biology of this important anti-inflammatory enzyme. ..
  42. International Conference-Structural Mechanisms in Muscle
    Avril Somlyo; Fiscal Year: 2004
    ..Approaches include single-molecule nanotechnology, synchrotron radiation and the genetic basis of disease, all of which will be exemplified in the topics discussed at the conference. ..
  43. Screen for Mycobacterium Tuberculosis (RMI)
    E White; Fiscal Year: 2005
    ..tuberculosis. 3) To study the effect of these novel inhibitors on the pantothenate pathway in M. smegmatis. 4) To co-crystallize these compounds with pantothenate synthetase to study their mode of binding ..
  44. Regulation of endothelial permeability via rhoA/ROCK
    JEROME BRESLIN; Fiscal Year: 2006
    ..We will also investigate how rhoA/ROCK inhibition affects these PMN-stimulated changes. This study will greatly increase our understanding of endothelial barrier regulation. [unreadable] [unreadable]..
  45. TNF Alters Renal Tubular Function in Diabetes
    Frank Gesek; Fiscal Year: 2005
    ..Complementary techniques are used to examine alterations in vivo and at the cellular level. Our studies provide insights into the earliest changes that occur in DT due to the cytokine TNF. ..
  46. Function of a Novel Matrix Junction in Endothelial Cells
    Jonathan Jones; Fiscal Year: 2005
    ..In aim 3, we will analyze the function(s) of components of the VMA in angiogenesis in vivo. These studies will provide new insight into the role of integrin/matrix interactions in angiogenesis. ..
  47. 'Fat' Nucleosides and Nucleotides
    RAMACHANDRA HOSMANE; Fiscal Year: 2005
    ..abstract_text> ..
  48. ISOLATION OF THE NEUROBLASTOMA PREDISPOSITION GENE
    John Maris; Fiscal Year: 2006
    ..Ultimately, these experiments should lead to the identification of a common pathway to neuroblastoma tumorigenesis that will be an outstanding target for rationally designed therapeutics. ..
  49. Azinomycins - Total Synthesis and Mechanism of Action
    Robert Coleman; Fiscal Year: 2007
    ..abstract_text> ..
  50. Purification of Optically Labeled Oligonucleotides
    William Pearson; Fiscal Year: 2004
    ..Initial work will focus on oligonucleotide probe purification. ..
  51. Hemodialysis Vascular Access Clinical Trial Consortium
    Arthur Greenberg; Fiscal Year: 2006
    ..This study is an attempt to reduce patient inconvenience and health care system expense by developing methods to prolong the lifespan of these connections. ..
  52. Mechanisms of acute bowel injury Role of NF-KB
    ISABELLE DE PLAEN; Fiscal Year: 2008
    ..This could prevent its progression toward irreversible intestinal damage and improve the survival of premature infants. [unreadable] [unreadable]..
  53. New Ligands for Radioimmunotherapy and MRI of Cancer
    Hyun Soon Chong; Fiscal Year: 2006
    ..The results of the proposed research will contribute to the development of better drugs for both MRI and RIT, which will greatly enhance clinical exploration of both modalities, and directly benefit cancer patients. ..
  54. GEORGETOWN UNIVERSITY-MEDSTAR CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE
    Joseph Verbalis; Fiscal Year: 2006
    ..The planning process will be led by a committee of faculty members who are leaders in translational research and clinical research training at the member institutions. [unreadable] [unreadable] [unreadable]..
  55. Asymmetric Synthesis of Cytotoxic Natural Products
    Robert Coleman; Fiscal Year: 2005
    ..abstract_text> ..
  56. Purification of Oligonucleotides and Nucleoside Triphosphates
    William Pearson; Fiscal Year: 2007
    ..The proposed work seeks to further develop an entirely new method for oligonucleotide purification, thus streamlining the development and production of these crucial substances. [unreadable] [unreadable] [unreadable]..