Genomes and Genes
Summary: Seven membered heterocyclic rings containing a NITROGEN atom.
Publications216 found, 100 shown here
- Targeting MYC dependence in cancer by inhibiting BET bromodomainsJennifer 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...
- Targeting MYCN in neuroblastoma by BET bromodomain inhibitionAlexandre 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...
- Small-molecule inhibition of BRDT for male contraceptionMartin 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...
- Myosin-II-dependent localization and dynamics of F-actin during cytokinesisKausalya 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...
- Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assaysMark 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...
- Drug-resistant aurora A mutants for cellular target validation of the small molecule kinase inhibitors MLN8054 and MLN8237Dominic A Sloane
Yorkshire Cancer Research Institute for Cancer Studies, University of Sheffield, UK
ACS Chem Biol 5:563-76. 2010....
- Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in miceMaxime 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...
- Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferaseStefan 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...
- Concentration-dependent modulation of amyloid-beta in vivo and in vitro using the gamma-secretase inhibitor, LY-450139Thomas 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...
- Besifloxacin, a novel fluoroquinolone, has broad-spectrum in vitro activity against aerobic and anaerobic bacteriaWolfgang 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...
- 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 diseaseYoko 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...
- 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 insomniaChristopher 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....
- Development of semagacestat (LY450139), a functional gamma-secretase inhibitor, for the treatment of Alzheimer's diseaseDavid 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...
- Myosin light chain kinase is involved in lipopolysaccharide-induced disruption of colonic epithelial barrier and bacterial translocation in ratsRaphael 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...
- Unexpected blockade of adipocyte differentiation by K-7174: implication for endoplasmic reticulum stressTsuyoshi 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...
- 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...
- Ca2+-store-dependent and -independent reversal of Stim1 localization and functionJeremy 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...
- Pharmacological properties of GABAA receptors containing gamma1 subunitsS 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...
- Phagocytosis of apoptotic and necrotic thymocytes is inhibited by PAF-receptor antagonists and affects LPS-induced COX-2 expression in murine macrophagesSoraya 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...
- Cyclic stretch-induced stress fiber dynamics - dependence on strain rate, Rho-kinase and MLCKChin 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...
- Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKLQiang 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...
- Securinine induces p73-dependent apoptosis preferentially in p53-deficient colon cancer cellsSonia 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...
- A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous systemRandall 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...
- Growth inhibition and differentiation of human breast cancer cells by the PAFR antagonist WEB-2086C 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...
- Efficacy of BET bromodomain inhibition in Kras-mutant non-small cell lung cancerTakeshi 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....
- WEB-2086 and WEB-2170 trigger apoptosis in both ATRA-sensitive and -resistant promyelocytic leukemia cells and greatly enhance ATRA differentiation potentialA Laurenzana
Department of Experimental Pathology and Oncology, University of Florence, Italy
Leukemia 19:390-5. 2005....
- Relative inhibitory potency of molinate and metabolites with aldehyde dehydrogenase 2: implications for the mechanism of enzyme inhibitionErin 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...
- Efficacy and safety of besifloxacin ophthalmic suspension 0.6% compared with moxifloxacin ophthalmic solution 0.5% for treating bacterial conjunctivitisMarguerite 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...
- Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294Yanqi 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...
- 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 peptChristopher 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...
- Suppression of cytokine response by GATA inhibitor K-7174 via unfolded protein responseYosuke 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...
- JNJ-39220675, a novel selective histamine H3 receptor antagonist, reduces the abuse-related effects of alcohol in ratsRuggero 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...
- Self-organized podosomes are dynamic mechanosensorsOlivier 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...
- Specific PAF antagonist WEB-2086 induces terminal differentiation of murine and human leukemia cellsCristina Cellai
Department of Experimental Pathology and Oncology, University of Florence, 50134, Firenze, Italy
FASEB J 16:733-5. 2002....
- Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraineT 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...
- Ocular pharmacokinetics of besifloxacin following topical administration to rabbits, monkeys, and humansJoel 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...
- Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular systemAndrea 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...
- Excellent tolerability but relatively low initial clinical efficacy of telcagepant in migrainePeer 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...
- Randomized, controlled trial of telcagepant for the acute treatment of migraineK 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...
- Securinine, a GABAA receptor antagonist, enhances macrophage clearance of phase II C. burnetii: comparison with TLR agonistsKirk 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...
- 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 trialTony 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...
- Myosin light-chain kinase contributes to short-term endothelial cell cytoskeletal alteration induced by serum from burned ratsBo Chen
Department of Pathophysiology, First Military Medical University, Guangzhou 510515, China
Di Yi Jun Yi Da Xue Xue Bao 24:481-4, 488. 2004....
- Phase III efficacy and safety study of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitisMichael 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...
- Besifloxacin ophthalmic suspension 0.6% in patients with bacterial conjunctivitis: A multicenter, prospective, randomized, double-masked, vehicle-controlled, 5-day efficacy and safety studyPaul 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...
- Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coliEmmanuelle 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...
- Nonclinical pharmacodynamics, pharmacokinetics, and safety of BOL-303224-A, a novel fluoroquinolone antimicrobial agent for topical ophthalmic useKeith 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...
- Structure of human cytidine deaminase bound to a potent inhibitorSang 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...
- Effects of a gamma-secretase inhibitor in a randomized study of patients with Alzheimer diseaseE 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...
- Growth cone collapse through coincident loss of actin bundles and leading edge actin without actin depolymerizationF 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...
- Potent inhibitors for the deamination of cytosine arabinoside and 5-aza-2'-deoxycytidine by human cytidine deaminaseJ 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...
- Selective inhibition of catalytic activity of smooth muscle myosin light chain kinaseM 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...
- Pre-clinical characterization of aryloxypyridine amides as histamine H3 receptor antagonists: identification of candidates for clinical developmentMichael 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...
- Bengamides revisited: new structures and antitumor studiesZ 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)...
- Safety, tolerability, and changes in amyloid beta concentrations after administration of a gamma-secretase inhibitor in volunteersEric 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...
- Mechanistic insight into WEB-2170-induced apoptosis in human acute myelogenous leukemia cells: the crucial role of PTENCristina 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...
- PAF antagonist treatment reduces pro-inflammatory cytokine mRNA after spinal cord injuryMary 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...
- Effects of anti-myosin drugs on anaphase chromosome movement and cytokinesis in crane-fly primary spermatocytesR 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...
- Myosin light chain kinase inhibitors induce retraction of mature oligodendrocyte processesMaría 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...
- 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-ylDaniel 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....
- A multigram chemical synthesis of the gamma-secretase inhibitor LY411575 and its diastereoisomersAbdul 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...
- 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]azThomas 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...
- Redundant mechanisms for anaphase chromosome movements: crane-fly spermatocyte spindles normally use actin filaments but also can function without themLacramioara Fabian
Biology Department, York University, Toronto, Ontario, Canada
Protoplasma 225:169-84. 2005....
- 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 mouseLynn A Hyde
Department of Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
J Pharmacol Exp Ther 319:1133-43. 2006....
- Platelet-activating factor stimulates ovine foetal pulmonary vascular smooth muscle cell proliferation: role of nuclear factor-kappa B and cyclin-dependent kinasesB 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...
- Laminin-311 (Laminin-6) fiber assembly by type I-like alveolar cellsPhillip 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...
- Implication of phosphorylation of the myosin II regulatory light chain in insulin-stimulated GLUT4 translocation in 3T3-F442A adipocytesYoung 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...
- An MLCK-dependent window in late G1 controls S phase entry of proliferating rodent hepatocytes via ERK-p70S6K pathwayAnne Bessard
INSERM U522, Unité de Recherches Hépatologiques IFR 140 Université de Rennes1, Rennes, France
Hepatology 44:152-63. 2006....
- Inhibiting myosin light chain kinase retards the growth of mammary and prostate cancer cellsLian 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...
- Myosin light chain kinase regulates synaptic plasticity and fear learning in the lateral amygdalaR 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...
- 9-cyano-1-azapaullone (cazpaullone), a glycogen synthase kinase-3 (GSK-3) inhibitor activating pancreatic beta cell protection and replicationHendrik 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...
- Inhibition of the myosin light chain kinase prevents hypoxia-induced blood-brain barrier disruptionChristoph 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...
- Dual role for myosin II in GLUT4-mediated glucose uptake in 3T3-L1 adipocytesF 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...
- [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...
- Theoretical and experimental investigation of calcium-contraction coupling in airway smooth musclePrisca 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...
- Phospholipase C and myosin light chain kinase inhibition define a common step in actin regulation during cytokinesisRaymond 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...
- The participation of the Na+-Ca2+ exchanger in primary cardiac myofibroblast migration, contraction, and proliferationJoshua 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...
- Organized migration of epithelial cells requires control of adhesion and protrusion through Rho kinase effectorsAnn M Hopkins
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, USA
Am J Physiol Gastrointest Liver Physiol 292:G806-17. 2007....
- Cellular mechanisms of mainstream cigarette smoke-induced lung epithelial tight junction permeability changes in vitroDorian 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...
- Interaction of non-adherent suspended neutrophils to complement opsonized pathogens: a new assay using optical trapsTomoko Suzuki
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai 980 8574, Japan
Cell Res 16:887-94. 2006....
- In vivo phosphorylation of regulatory light chain of myosin II in sea urchin eggs and its role in controlling myosin localization and function during cytokinesisRyota 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...
- Calcium absorption by Cav1.3 induces terminal web myosin II phosphorylation and apical GLUT2 insertion in rat intestineOliver J Mace
Department of Biology, The University of York, York YO10 5YW, UK
J Physiol 580:605-16. 2007....
- Role of platelet-activating factor in phosphatidylcholine secretion in primary cultures of rat type II pneumocytesE 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...
- Proteinase-activated receptor-2-induced colonic inflammation in mice: possible involvement of afferent neurons, nitric oxide, and paracellular permeabilityNicolas 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...
- Myofibrillogenesis in the first cardiomyocytes formed from isolated quail precardiac mesodermAiping Du
Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6058, USA
Dev Biol 257:382-94. 2003....
- Functional diversity between Rho-kinase- and MLCK-mediated cytoskeletal actions in a myofibroblast-like hepatic stellate cell lineMikio 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...
- Preventive effect of platelet-activating factor antagonist, Y-24180, against cyclosporine-induced acute nephrotoxicityA 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...
- ML-7 inhibits exocytosis of superoxide-producing intracellular compartments in human neutrophils stimulated with phorbol myristate acetate in a myosin light chain kinase-independent mannerKeita Odani
Department of Radiology, Kochi Medical School, Nankoku, 783 5305 Kochi, Japan
Histochem Cell Biol 119:363-70. 2003....
- Parallel liquid synthesis of N,N'-Disubstituted 3-amino azepin-2-ones as potent and specific farnesyl transferase inhibitorsThierry 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...
- Dependence of metastatic cancer cell invasion on MLCK-catalyzed phosphorylation of myosin regulatory light chainR Tohtong
Department of Biochemistry, Faculty of Science, Mahidol University, Phya Thai, Bangkok, Thailand
Prostate Cancer Prostatic Dis 6:212-6. 2003....
- Degranulation in RBL-2H3 cells: regulation by calmodulin pathwayMasayuki 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....
- Role of the actin cytoskeleton in regulating endothelial permeability in venulesJ 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...
- Synthesis of N,N'-disubstituted 3-aminobenzo[c] and [d]azepin-2-ones as potent and specific farnesyl transferase inhibitorsThierry 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...
- Rapid actin transport during cell protrusionDaniel 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...
- Inhibition of contractile activation reduces reoxygenation-induced endothelial gap formationC 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)...
- PAF- and bradykinin-induced hyperpermeability of rat venules is independent of actin-myosin contractionR 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...
- Cyclic AMP-dependent protein kinase A plays a role in the directed migration of human keratinocytes in a DC electric fieldC 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...
- Participation of prostaglandin E2 and platelet-activating factor in thapsigargin-induced production of interleukin-6Gaku 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...
- Myosin light chain phosphorylation in neutrophil-stimulated coronary microvascular leakageSarah 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...
- Myosin light chain kinase inhibitors can block invasion and adhesion of human pancreatic cancer cell linesKenzo 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...
- The renal effects of Bothrops jararacussu venom and the role of PLA(2) and PAF blockersA 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...
- Platelet-activating factor antagonists decrease the inflammatory nociceptive response in ratsLisa 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...
- N-Heterocycles from Azides through Rhodium-Catalyzed Nitrenoid TransferTOM GREGORY DRIVER; Fiscal Year: 2012..or o-anthranil decomposition to enable the rapid synthesis of heteroaromatic carbazoles, indoles, functionalized azepines, and aziridines...
- ROUTES TO CHIRAL CARBOCYCLIC AND HETEROCYCLIC COMPOUNDSA 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 ..
- Neuropsychopharmacol Interactions - Cocaine & SerotoninKATHRYN 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. ..
- Targeted Proteomics of Stress and AddictionKATHRYN CUNNINGHAM; Fiscal Year: 2005..abstract_text> ..
- NEUROBEHAVIORAL PHARMACOLOGY OF STIMULANTSKathryn A Cunningham; Fiscal Year: 2010....
- NEUROPSYCHOPHARMACOLOGY MDMA--MONOAMINERGIC MECHANISMSKATHRYN CUNNINGHAM; Fiscal Year: 2005..abstract_text> ..
- INTERESTING BIOACTIVE SUBSTANCESDavid Williams; Fiscal Year: 2006..The selective synthesis of contiguous stereotriads will advance basic methodology for asymmetric conjugate additions. ..
- CHEMICAL SYNTHESIS OF NOVEL NATURAL PRODUCTSDavid 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. ..
- Micropallet Arrays for Separation of Single Cells and ColoniesNancy 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. ..
- Computer-aided Design of Anti-cancer Drugs Targeting Protein KinasesChung 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]..
- Significance of Genetic Alterations in NeuroblastomaJohn Maris; Fiscal Year: 2006..It is expected that these will be of prognostic importance and serve as specific targets for developmental therapeutics. ..
- Tandem Cycloaddition Chemistry of 2-AzoniaheterodienesSCOTT DENMARK; Fiscal Year: 2007..abstract_text> ..
- An Automated Platform for Kinase Assays on Patient CellsNancy Allbritton; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- Mechanistic Studies of Anti-HIV Activity of a Novel Ring-Expanded NucleosideRAMACHANDRA 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]..
- METHODOLOGY FOR THE SYNTHESIS OF NITROGEN HETEROCYCLESPhilip 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]..
- Phase I Radiosensitization Study of GW572016 in Recurrent Breast CancerELIZABETH DEES; Fiscal Year: 2007..This proposal pilots a novel combination therapy to treat this common and challenging clinical problem. [unreadable] [unreadable] [unreadable]..
- CGRP Regulation of iNOS and MAP Kinases/Phosphatases in Trigeminal Ganglia GliaPaul L Durham; Fiscal Year: 2010....
- Enteropathogenic E. coli Effects on Intestinal FunctionGail 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. ..
- HYPONATREMIA-INDUCED OSTEOPOROSISJoseph G Verbalis; Fiscal Year: 2010....
- Cross-Coupling Reactions of OrganosilanolsSCOTT 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. ..
- Control of Genomic Stability by Emi1 and SecurinNORMAN LEHMAN; Fiscal Year: 2007..abstract_text> ..
- Anti-plague agents targeting YopH of Yersinia PestisChung 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]..
- CATCH: Mechanochemistry and Regulation in Smooth MuscleThomas 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. ..
- BOLD and Perfusion fMRI of Alzheimer's Disease RiskAdam Fleisher; Fiscal Year: 2008....
- Structural Biology of Cardiovascular SignalingAvril Somlyo; Fiscal Year: 2008..abstract_text> ..
- Rapid Analysis of Signaling in Adherent CellsNancy Allbritton; Fiscal Year: 2008....
- CGRP CONTROL IN TRIGEMINAL NEURONS IN VITRO AND IN VIVOPaul Durham; Fiscal Year: 2006..abstract_text> ..
- P450 PHENOTYPE AND CHEMOTHERAPY TOXICITY IN THE ELDERLYELIZABETH 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. ..
- BRAIN OXYTOCIN AND ETHANOL EFFECT ON INGESTIVE BEHAVIORJoseph Verbalis; Fiscal Year: 2001....
- Profiling Ras Activated Signal Transduction PathwaysNancy 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. ..
- LIPOPHILIC ANTIFOLATES AND AIDS OPPORTUNISTIC INFECTIONSAndre 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. ..
- SYNTHESIS OF DIAZONAMIDESPhilip 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. ..
- SIGNAL TRANSDUCTION THROUGH CALCIUM WAVESNancy Allbritton; Fiscal Year: 2003....
- NOVEL APPROACHES TO ANTIFOLATE CHEMOTHERAPYAndre 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. ..
- DISSECTING ENZYMATIC NETWORKS IN SINGLE NEURONSNancy 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. ..
- PHYSIOLOGICAL ADAPTATION TO SUSTAINED HYPO-OSMOLALITYJoseph 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. ..
- NOVEL ORGANIC REAGENTS FOR BIOMEDICAL APPLICATIONSRAMACHANDRA HOSMANE; Fiscal Year: 2002..abstract_text> ..
- Nitric Oxide Control of CGRP in Trigeminal NeuronsPaul Durham; Fiscal Year: 2002..abstract_text> ..
- SYNTHESIS OF NOVEL BIOLOGICALLY ACTIVE NATURAL PRODUCTSROBERT 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. ..
- MEASUREMENT OF KINASE ACTIVITIES IN SINGLE TUMOR CELLSNancy Allbritton; Fiscal Year: 2001..When fully developed, this integrated microchip will represent a new paradigm in single-cell measurement techniques. ..
- Anti-Inflammatory PAF Acetylhydrolase in Lung InjuryKatherine 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. ..
- International Conference-Structural Mechanisms in MuscleAvril 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. ..
- 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 ..
- Regulation of endothelial permeability via rhoA/ROCKJEROME 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]..
- TNF Alters Renal Tubular Function in DiabetesFrank 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. ..
- Function of a Novel Matrix Junction in Endothelial CellsJonathan 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. ..
- 'Fat' Nucleosides and NucleotidesRAMACHANDRA HOSMANE; Fiscal Year: 2005..abstract_text> ..
- ISOLATION OF THE NEUROBLASTOMA PREDISPOSITION GENEJohn 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. ..
- Azinomycins - Total Synthesis and Mechanism of ActionRobert Coleman; Fiscal Year: 2007..abstract_text> ..
- Purification of Optically Labeled OligonucleotidesWilliam Pearson; Fiscal Year: 2004..Initial work will focus on oligonucleotide probe purification. ..
- Hemodialysis Vascular Access Clinical Trial ConsortiumArthur 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. ..
- Mechanisms of acute bowel injury Role of NF-KBISABELLE DE PLAEN; Fiscal Year: 2008..This could prevent its progression toward irreversible intestinal damage and improve the survival of premature infants. [unreadable] [unreadable]..
- New Ligands for Radioimmunotherapy and MRI of CancerHyun 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. ..
- GEORGETOWN UNIVERSITY-MEDSTAR CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCEJoseph 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]..
- Asymmetric Synthesis of Cytotoxic Natural ProductsRobert Coleman; Fiscal Year: 2005..abstract_text> ..
- Purification of Oligonucleotides and Nucleoside TriphosphatesWilliam 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]..