enzyme inhibitors

Summary

Summary: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

Top Publications

  1. ncbi Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death
    Alexander Arlt
    1Laboratory of Molecular Gastroenterology and Hepatology, 1st Department of Medicine, University of Kiel, Germany
    Oncogene 22:3243-51. 2003
  2. pmc Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer
    Arkaitz Carracedo
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 118:3065-74. 2008
  3. pmc Inhibition of macroautophagy triggers apoptosis
    Patricia Boya
    CNRS UMR 8125, Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Mol Cell Biol 25:1025-40. 2005
  4. ncbi Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex
    X Nan
    Institute of Cell and Molecular Biology, University of Edinburgh, UK
    Nature 393:386-9. 1998
  5. pmc SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
    B L Bennett
    Signal Research Division, Celgene Corporation, 5555 Oberlin Drive, San Diego, CA 92121 USA
    Proc Natl Acad Sci U S A 98:13681-6. 2001
  6. pmc Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells
    M Gottlicher
    Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, H v Helmholtz Platz 1, D 76344 Eggenstein, Germany
    EMBO J 20:6969-78. 2001
  7. ncbi Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt
    L del Peso
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Science 278:687-9. 1997
  8. ncbi Epigenetic programming by maternal behavior
    Ian C G Weaver
    Douglas Hospital Research Center, 6875 LaSalle Blvd, Montreal, Quebec H4H 1R3, Canada
    Nat Neurosci 7:847-54. 2004
  9. ncbi Neuraminidase inhibitors for influenza
    Anne Moscona
    Department of Pediatrics, Weill Medical College of Cornell University, New York, NY 10021, USA
    N Engl J Med 353:1363-73. 2005
  10. ncbi 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response
    Jeremy W Tomlinson
    Endocrinology, Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2TH, UK
    Endocr Rev 25:831-66. 2004

Research Grants

Detail Information

Publications311 found, 100 shown here

  1. ncbi Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death
    Alexander Arlt
    1Laboratory of Molecular Gastroenterology and Hepatology, 1st Department of Medicine, University of Kiel, Germany
    Oncogene 22:3243-51. 2003
    ....
  2. pmc Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer
    Arkaitz Carracedo
    Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, Massachusetts, USA
    J Clin Invest 118:3065-74. 2008
    ....
  3. pmc Inhibition of macroautophagy triggers apoptosis
    Patricia Boya
    CNRS UMR 8125, Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Mol Cell Biol 25:1025-40. 2005
    ..All together, these data indicate that autophagy may be cytoprotective, at least under conditions of nutrient depletion, and point to an important cross talk between type 1 and type 2 cell death pathways...
  4. ncbi Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex
    X Nan
    Institute of Cell and Molecular Biology, University of Edinburgh, UK
    Nature 393:386-9. 1998
    ..The data suggest that two global mechanisms of gene regulation, DNA methylation and histone deacetylation, can be linked by MeCP2...
  5. pmc SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
    B L Bennett
    Signal Research Division, Celgene Corporation, 5555 Oberlin Drive, San Diego, CA 92121 USA
    Proc Natl Acad Sci U S A 98:13681-6. 2001
    ..Our study supports targeting JNK as an important strategy in inflammatory disease, apoptotic cell death, and cancer...
  6. pmc Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells
    M Gottlicher
    Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, H v Helmholtz Platz 1, D 76344 Eggenstein, Germany
    EMBO J 20:6969-78. 2001
    ..More over, tumor growth and metastasis formation are significantly reduced in animal experiments. Therefore, valproic acid might serve as an effective drug for cancer therapy...
  7. ncbi Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt
    L del Peso
    Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Science 278:687-9. 1997
    ..Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway...
  8. ncbi Epigenetic programming by maternal behavior
    Ian C G Weaver
    Douglas Hospital Research Center, 6875 LaSalle Blvd, Montreal, Quebec H4H 1R3, Canada
    Nat Neurosci 7:847-54. 2004
    ..Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible...
  9. ncbi Neuraminidase inhibitors for influenza
    Anne Moscona
    Department of Pediatrics, Weill Medical College of Cornell University, New York, NY 10021, USA
    N Engl J Med 353:1363-73. 2005
  10. ncbi 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response
    Jeremy W Tomlinson
    Endocrinology, Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2TH, UK
    Endocr Rev 25:831-66. 2004
    ..Therapeutic inhibition of 11beta-HSD1 reductase activity in patients with obesity and the metabolic syndrome, as well as in glaucoma and osteoporosis, remains an exciting prospect...
  11. ncbi SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27
    A C Carrano
    Department of Pathology, New York University Medical Center, New York 10016, USA
    Nat Cell Biol 1:193-9. 1999
    ..Thus, p27 degradation is subject to dual control by the accumulation of both SKP2 and cyclins following mitogenic stimulation...
  12. pmc The 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor INCB13739 improves hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapy
    Julio Rosenstock
    Dallas Diabetes and Endocrine Center at Medical City, Dallas, Texas, USA
    Diabetes Care 33:1516-22. 2010
    ..The efficacy and safety of the 11betaHSD1 inhibitor INCB13739 were assessed when added to ongoing metformin monotherapy in patients with type 2 diabetes exhibiting inadequate glycemic control (A1C 7-11%)...
  13. pmc Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol
    Pal Pacher
    Laboratory of Physiological Studies, National Institute on Alcohol Aabuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane MSC 9413, Room 2N 17, Bethesda, Maryland 20892 9413, USA
    Pharmacol Rev 58:87-114. 2006
    ..Here we present a critical overview of the effects of XO inhibitors in various pathophysiological conditions and also review the various emerging therapeutic strategies offered by this approach...
  14. ncbi EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy
    J Guillermo Paez
    Departments of Medical Oncology and Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 304:1497-500. 2004
    ..These results suggest that EGFR mutations may predict sensitivity to gefitinib...
  15. ncbi PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest
    Jiyong Liang
    Molecular and Cell Biology, Sunnybrook and Women s College Health Sciences Centre, St Mary s Hospital, McGill University, Montreal, Quebec
    Nat Med 8:1153-60. 2002
    ..Thus, we show a novel mechanism whereby Akt impairs p27 function that is associated with an aggressive phenotype in human breast cancer...
  16. pmc The secretases: enzymes with therapeutic potential in Alzheimer disease
    Bart De Strooper
    Center for Human Genetics, VIB and KULeuven, Herestraat 49, Leuven, Belgium
    Nat Rev Neurol 6:99-107. 2010
    ..Success or failure of these first-generation AD therapies will have enormous consequences for further drug development efforts for AD and possibly other neurodegenerative conditions...
  17. ncbi 5-Azacytidine and 5-aza-2'-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy
    Judith K Christman
    Department of Biochemistry and Molecular Biology and UNMC Eppley Cancer Center, University of Nebraska Medical Center, 984525 University Medical Center, Omaha, Nebraska, NE 68198 4525, USA
    Oncogene 21:5483-95. 2002
    ..The implications of these mechanistic studies for development of less toxic inhibitors of DNA methylation are discussed...
  18. pmc The specificities of protein kinase inhibitors: an update
    Jenny Bain
    Division of Signal Transduction Therapy, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 371:199-204. 2003
    ..33 microM) and p38-regulated/activated kinase (PRAK; IC(50)=1.0 microM)...
  19. ncbi PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients
    Yoichi Nagata
    Department of Surgical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Cell 6:117-27. 2004
    ..Thus, PTEN deficiency is a powerful predictor for trastuzumab resistance. Additionally, PI3K inhibitors rescued PTEN loss-induced trastuzumab resistance, suggesting that PI3K-targeting therapies could overcome this resistance...
  20. ncbi Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation
    K P Hoeflich
    Ontario Cancer Institute Princess Margaret Hospital, Toronto, Canada
    Nature 406:86-90. 2000
    ..Thus, GSK-3beta facilitates NF-kappaB function...
  21. ncbi Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription
    Karanam Balasubramanyam
    Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India
    J Biol Chem 279:51163-71. 2004
    ..Thus, non-toxic curcumin, which targets p300/CBP, may serve as a lead compound in combinatorial HIV therapeutics...
  22. pmc Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation
    V M Richon
    DeWitt Wallace Research Laboratory, Cell Biology Program, Memorial Sloan Kettering Cancer Center and Graduate School of Medical Sciences of Cornell Medical School, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 97:10014-9. 2000
    ..Thus, the present findings indicate that the induction of p21(WAF1) by SAHA is regulated, at least in part, by the degree of acetylation of the gene-associated histones and that this induced increase in acetylation is gene selective...
  23. ncbi Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer
    Jiang Shou
    The Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
    J Natl Cancer Inst 96:926-35. 2004
    ..We used a breast cancer model system with high expression of AIB1 and HER2 to investigate the possible mechanisms underlying this resistance...
  24. ncbi PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization
    Incheol Shin
    Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
    Nat Med 8:1145-52. 2002
    ..These data indicate that Akt may contribute to tumor-cell proliferation by phosphorylation and cytosolic retention of p27, thus relieving CDK2 from p27-induced inhibition...
  25. ncbi A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
    M Enari
    Department of Genetics, Osaka University Medical School, Suita, Japan
    Nature 391:43-50. 1998
    ....
  26. ncbi Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition
    Nuala McCabe
    Cancer Research UK Gene Function and Regulation Group and The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom
    Cancer Res 66:8109-15. 2006
    ....
  27. pmc 11beta-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice
    Anne Hermanowski-Vosatka
    Merck Research Laboratories, Merck and Company, Rahway, NJ 07065, USA
    J Exp Med 202:517-27. 2005
    ....
  28. pmc A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages
    N Araki
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Cell Biol 135:1249-60. 1996
    ..These findings indicate that PI 3-kinase is not necessary for receptor-mediated stimulation of pseudopod extension, but rather functions in the closure of macropinosomes and phagosomes into intracellular organelles...
  29. pmc Forkhead transcription factor FKHR-L1 modulates cytokine-dependent transcriptional regulation of p27(KIP1)
    P F Dijkers
    Departments of Pulmonary Diseases, The Netherlands
    Mol Cell Biol 20:9138-48. 2000
    ..Taken together, these observations indicate that inhibition of p27(KIP1) transcription through PI3K-induced FKHR-L1 phosphorylation provides a novel mechanism of regulating cytokine-mediated survival and proliferation...
  30. ncbi GSK-3-selective inhibitors derived from Tyrian purple indirubins
    Laurent Meijer
    CNRS, Cell Cycle Group, Station Biologique, BP 74, 29682 Roscoff Cedex, Bretagne, France
    Chem Biol 10:1255-66. 2003
    ..BIO but not 1-methyl-BIO closely mimicked Wnt signaling in Xenopus embryos. 6-bromoindirubins thus provide a new scaffold for the development of selective and potent pharmacological inhibitors of GSK-3...
  31. ncbi Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5
    L Meijer
    CNRS, Station Biologique, Roscoff, France
    Eur J Biochem 243:527-36. 1997
    ..Through its unique selectivity for some cyclin-dependent kinases, roscovitine provides a useful antimitotic reagent for cell cycle studies and may prove interesting to control cells with deregulated cdc2, cdk2 or cdk5 kinase activities...
  32. ncbi Histone deacetylase inhibitors: overview and perspectives
    Milos Dokmanovic
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Mol Cancer Res 5:981-9. 2007
    ..A hypothesis is presented to explain the relative resistance of normal cells to HDACi-induced cell death...
  33. ncbi Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors
    M S Finnin
    Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 401:188-93. 1999
    ..These structures also suggest a mechanism for the deacetylation reaction and provide a framework for the further development of HDAC inhibitors as antitumour agents...
  34. pmc SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1
    Michelle Pacholec
    Department of Cardiovascular, Pfizer Global Research and Development, Groton, Connecticut 06340, USA
    J Biol Chem 285:8340-51. 2010
    ..Taken together, we conclude that SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1...
  35. doi The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer
    Adrian J Folkes
    Piramed Pharma, 957 Buckingham Avenue, Slough, Berks SL1 4NL, United Kingdom
    J Med Chem 51:5522-32. 2008
    ..This work resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer...
  36. ncbi Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant
    Sabine Heumüller
    Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe Universitat, Theodor Stern Kai 7, D 60596 Frankfurt am Main, Germany
    Hypertension 51:211-7. 2008
    ..These observations indicate that apocynin predominantly acts as an antioxidant in endothelial cells and vascular smooth muscle cells and should not be used as an NADPH oxidase inhibitor in vascular systems...
  37. ncbi Role of p38 mitogen-activated protein kinase in a murine model of pulmonary inflammation
    J A Nick
    Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA
    J Immunol 164:2151-9. 2000
    ....
  38. ncbi ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models
    Cherrie K Donawho
    Abbott Laboratories, Abbott Park, Illinois 60064 6074, USA
    Clin Cancer Res 13:2728-37. 2007
    ..To evaluate the preclinical pharmacokinetics and antitumor efficacy of a novel orally bioavailable poly(ADP-ribose) polymerase (PARP) inhibitor, ABT-888...
  39. ncbi Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro
    Susan M Graham
    Department of Medicine, Royal Infirmary, Glasgow, Scotland
    Blood 99:319-25. 2002
    ..Despite dramatic short-term responses in vivo, such in vitro insensitivity to STI571, in combination with its demonstrated antiproliferative activity, could translate into disease relapse after prolonged therapy...
  40. ncbi Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia
    B J Druker
    Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA
    N Engl J Med 344:1031-7. 2001
    ..Since tyrosine kinase activity is essential to the transforming function of BCR-ABL, an inhibitor of the kinase could be an effective treatment for CML...
  41. ncbi Crystal structure of mitochondrial respiratory membrane protein complex II
    Fei Sun
    Tsinghua IBP Joint Research Group for Structural Biology, Tsinghua University, Beijing 100084, China
    Cell 121:1043-57. 2005
    ..The Complex II structure provides a bona fide model for study of the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex...
  42. ncbi Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol
    T Hofmann
    Institut fur Pharmakologie, Universitatsklinikum Benjamin Franklin, Freie Universitat Berlin, Germany
    Nature 397:259-63. 1999
    ..Thus, hTRPC3 and hTRPC6 represent the first members of a new functional family of second-messenger-operated cation channels, which are activated by diacylglycerol...
  43. ncbi Topoisomerase I inhibitors: camptothecins and beyond
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892 4255, USA
    Nat Rev Cancer 6:789-802. 2006
    ....
  44. pmc A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling
    Zachary A Knight
    Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    Cell 125:733-47. 2006
    ..These results illustrate systematic target validation using a matrix of inhibitors that span a protein family...
  45. ncbi Regulation of TNF-alpha-induced reorganization of the actin cytoskeleton and cell-cell junctions by Rho, Rac, and Cdc42 in human endothelial cells
    B Wojciak-Stothard
    Ludwig Institute for Cancer Research, London, United Kingdom
    J Cell Physiol 176:150-65. 1998
    ..Our data suggest that Cdc42, Rac, and Rho are activated in a hierarchical cascade following stimulation with TNF-alpha leading to actomyosin-mediated cell retraction and formation of intercellular gaps...
  46. ncbi Membrane prostaglandin E synthase-1: a novel therapeutic target
    Bengt Samuelsson
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77, Stockholm, Sweden
    Pharmacol Rev 59:207-24. 2007
    ..These findings indicate that mPGES-1 is a potential target for the development of therapeutic agents for treatment of several diseases...
  47. pmc STIM1, an essential and conserved component of store-operated Ca2+ channel function
    Jack Roos
    Torrey Pines Therapeutics, Inc, La Jolla, CA 92037, USA
    J Cell Biol 169:435-45. 2005
    ..We propose that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels...
  48. pmc Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation
    Carlos Solorzano
    Department of Pharmacology, University of California, Irvine, CA 92697 4624, USA
    Proc Natl Acad Sci U S A 106:20966-71. 2009
    ..The PEA-hydrolyzing amidase NAAA may provide a previously undescribed target for antiinflammatory medicines...
  49. ncbi Miglustat for treatment of Niemann-Pick C disease: a randomised controlled study
    Marc C Patterson
    Department of Neurology and Pediatrics, Columbia University, NY, USA
    Lancet Neurol 6:765-72. 2007
    ..Miglustat is able to cross the blood-brain barrier, and is thus a potential therapy for neurological diseases. We aimed to establish the effect of miglustat on several markers of NPC severity...
  50. pmc Comparative pharmacology of chemically distinct NADPH oxidase inhibitors
    S Wind
    Rudolf Buchheim Institute for Pharmacology, Justus Liebig University, Giessen, Germany
    Br J Pharmacol 161:885-98. 2010
    ..One of these sources may be NADPH oxidases. However, due to increasing concerns about the specificity of the compounds commonly used as NADPH oxidase inhibitors, data obtained with these compounds may have to be re-interpreted...
  51. ncbi Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes
    Birgit Heltweg
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Cancer Res 66:4368-77. 2006
    ..Cambinol was well tolerated in mice and inhibited growth of Burkitt lymphoma xenografts. Inhibitors of NAD-dependent deacetylases may constitute novel anticancer agents...
  52. ncbi Class II histone deacetylases act as signal-responsive repressors of cardiac hypertrophy
    Chun Li Zhang
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas 75390, USA
    Cell 110:479-88. 2002
    ..Thus, class II HDACs act as signal-responsive suppressors of the transcriptional program governing cardiac hypertrophy and heart failure...
  53. pmc Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake
    Su Gao
    Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 104:17358-63. 2007
    ..Together, these findings highlight site-specific impacts of hypothalamic ACC activation in leptin's anorectic signaling cascade...
  54. ncbi Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain
    H F Dovey
    Elan Pharmaceuticals, Inc, South San Francisco, CA 94080, USA
    J Neurochem 76:173-81. 2001
    ..Development of such novel functional gamma-secretase inhibitors will enable a clinical examination of the A beta hypothesis that Ass peptide drives the neuropathology observed in Alzheimer's disease...
  55. ncbi Activation of the PI3K/Akt pathway and chemotherapeutic resistance
    Kip A West
    Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Building 8, Room 5101, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA
    Drug Resist Updat 5:234-48. 2002
    ..Specifically inhibiting Akt activity may be a valid approach to treat cancer and increase the efficacy of chemotherapy...
  56. ncbi Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study
    Olivier Rixe
    Pitie Salpetriere Hospital, University of Paris, Paris, France
    Lancet Oncol 8:975-84. 2007
    ..We aimed to assess the activity and safety of axitinib in patients with metastatic renal-cell cancer who had failed on previous cytokine-based treatment...
  57. pmc A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol
    Jacqueline L Blankman
    The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Chem Biol 14:1347-56. 2007
    ..Interestingly, MAGL, ABHD6, and ABHD12 display distinct subcellular distributions, suggesting that they may control different pools of 2-AG in the nervous system...
  58. pmc Mycobacterium tuberculosis Rv3802c encodes a phospholipase/thioesterase and is inhibited by the antimycobacterial agent tetrahydrolipstatin
    Sarah K Parker
    Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, United States of America
    PLoS ONE 4:e4281. 2009
    ..tuberculosis pathogenesis, identification of a novel cell wall enzyme and its inhibition has therapeutic and diagnostic implications...
  59. pmc β- but not γ-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia
    Robert Tamayev
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
    EMBO Mol Med 4:171-9. 2012
    ..Our data and the failures of anti-Aβ therapies in humans advise against targeting γ-secretase cleavage of APP and/or Aβ...
  60. ncbi The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer
    Hae Young Yong
    Duksung Women s University, College of Pharmacy, Seoul, Korea
    Expert Opin Investig Drugs 18:1893-905. 2009
    ....
  61. doi Infections with oseltamivir-resistant influenza A(H1N1) virus in the United States
    Nila J Dharan
    Epidemic Intelligence Service, Office of Workforce and Career Development Assigned to Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS A 32, Atlanta, GA 30333, USA
    JAMA 301:1034-41. 2009
    ..Early surveillance data suggest that the prevalence of oseltamivir resistance among A(H1N1) viruses will most likely be higher during the 2008-2009 season...
  62. ncbi Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
    S Imai
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 403:795-800. 2000
    ..These findings provide a molecular framework of NAD-dependent histone deacetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes...
  63. ncbi BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics
    S L Roberds
    Department of Genomics, Pharmacia Corp, 301 Henrietta Street, Kalamazoo, MI 49007, USA
    Hum Mol Genet 10:1317-24. 2001
    ....
  64. ncbi Transglutaminase 2 inhibitor, KCC009, disrupts fibronectin assembly in the extracellular matrix and sensitizes orthotopic glioblastomas to chemotherapy
    L Yuan
    Department of Neurological Surgery, Washington University School of Medicine, St Louis, MO, USA
    Oncogene 26:2563-73. 2007
    ....
  65. ncbi A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
    T T Paull
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0540, USA
    Curr Biol 10:886-95. 2000
    ..Recently it has been reported that a member of the histone H2A family, H2AX, becomes extensively phosphorylated within 1-3 minutes of DNA damage and forms foci at break sites...
  66. pmc Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor
    Erin M Bowers
    Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Chem Biol 17:471-82. 2010
    ..Inhibition of histone acetylation and cell growth by C646 in cells validate its utility as a pharmacologic probe and suggest that p300/CBP HAT is a worthy anticancer target...
  67. ncbi Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation
    F G Gervais
    Department of Pharmacology, Biochemistry, and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Merck Research Laboratories, Kirkland, Quebec, Canada
    Cell 97:395-406. 1999
    ..Caspases thus appear to play a dual role in proteolytic processing of APP and the resulting propensity for A beta peptide formation, as well as in the ultimate apoptotic death of neurons in Alzheimer's disease...
  68. ncbi A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells
    Edgar R Wood
    Department of Computational, Analytical and Structural Sciences, GlaxoSmithKline, Inc, Research Triangle Park, North Carolina 27709, USA
    Cancer Res 64:6652-9. 2004
    ..The differences in the off-rates of these drugs and the ability of GW572016 to inhibit ErbB-2 can be explained by the enzyme-inhibitor structures...
  69. pmc Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)
    Linda Vermeulen
    Department of Molecular Biology, University of Gent VIB, K L Ledeganckstraat 35, B 9000 Gent, Belgium
    EMBO J 22:1313-24. 2003
    ..This effect represents, together with phosphorylation of nucleosome components such as histone H3, an essential step leading to selective transcriptional activation of NF-kappaB-dependent gene expression...
  70. ncbi Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis
    Haim Y Cohen
    Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115 USA
    Mol Cell 13:627-38. 2004
    ..We demonstrate that increased acetylation of Ku70 disrupts the Ku70-Bax interaction and coincides with cytoplasmic accumulation of CBP. These results shed light on the role of acetyltransferases as tumor suppressors...
  71. ncbi New insights on the use of desipramine as an inhibitor for acid ceramidase
    Saeed Elojeimy
    Department of Microbiology and Immunology, Medical University of South Carolina, P O Box 250504, 173 Ashley Avenue, Charleston, SC 29425, USA
    FEBS Lett 580:4751-6. 2006
    ..This study reveals a new mechanism of action for desipramine...
  72. ncbi Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors
    Purva Bali
    Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida 33612, USA
    J Biol Chem 280:26729-34. 2005
    ..Depletion of HDAC6 sensitized human leukemia cells to HAA-HDIs and proteasome inhibitors...
  73. ncbi Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells
    P A Marks
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Natl Cancer Inst 92:1210-6. 2000
    ..The hydroxamic acid-based HPCs are potentially effective agents for cancer therapy and, possibly, cancer chemoprevention...
  74. doi Crystal structures of anaplastic lymphoma kinase in complex with ATP competitive inhibitors
    Roberto T Bossi
    Nerviano Medical Sciences S r l, Viale Pasteur 10, 20014 Nerviano MI, Italy
    Biochemistry 49:6813-25. 2010
    ..Finally, mapping of the activating mutations associated with neuroblastoma onto our structures may explain the roles these residues have in the activation process...
  75. pmc Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest
    R A Fratti
    Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    J Cell Biol 154:631-44. 2001
    ..tuberculosis. This study also identifies mycobacterial phosphoinositides as products with specialized toxic properties, interfering with discrete trafficking stages in phagosomal maturation...
  76. ncbi Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivity
    Johannes M Aerts
    Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Diabetes 56:1341-9. 2007
    ....
  77. pmc Activity of any class IA PI3K isoform can sustain cell proliferation and survival
    Lazaros C Foukas
    Centre for Cell Signalling, Institute of Cancer, Queen Mary University of London, London EC1M 6BQ, United Kingdom
    Proc Natl Acad Sci U S A 107:11381-6. 2010
    ..Such functional redundancy of class IA PI3K isoforms upon sustained PI3K inhibition has implications for the development and use of PI3K inhibitors in cancer...
  78. pmc Gilenya (FTY720) inhibits acid sphingomyelinase by a mechanism similar to tricyclic antidepressants
    Glyn Dawson
    Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA
    Biochem Biophys Res Commun 404:321-3. 2011
    ....
  79. doi High level soluble production of functional ribonuclease inhibitor in Escherichia coli by fusing it to soluble partners
    Wanhua Guo
    Department of Nuclear Medicine, Nanjing University, Nanjing 210008, People s Republic of China
    Protein Expr Purif 77:185-92. 2011
    ..And a convenient two-step immobilized metal affinity chromatography (IMAC) method has been implemented in our study, comparing with the traditional RNase A affinity chromatography method...
  80. pmc Histone deacetylase inhibitors induce remission in transgenic models of therapy-resistant acute promyelocytic leukemia
    L Z He
    Molecular Biology Program and Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Division, Graduate School of Medical Sciences, Cornell University, New York, New York 10021, USA
    J Clin Invest 108:1321-30. 2001
    ..In vivo, HDACIs induced accumulation of acetylated histones in target organs. Strikingly, this combination of agents induced leukemia remission and prolonged survival, without apparent toxic side effects...
  81. doi Discovery of adamantyl ethanone derivatives as potent 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors
    Xiangdong Su
    Medicinal Chemistry, Department of Pharmacy and Pharmacology and Sterix Ltd, University of Bath, Bath BA2 7AY, UK
    ChemMedChem 5:1026-44. 2010
    ..Comparison of the publicly available X-ray crystal structures of human 11beta-HSD1 led to docking studies of the potent compounds, revealing how these molecules may interact with the enzyme and cofactor...
  82. doi Endocrine resistance associated with activated ErbB system in breast cancer cells is reversed by inhibiting MAPK or PI3K/Akt signaling pathways
    Sandra E Ghayad
    Universite de Lyon, France
    Int J Cancer 126:545-62. 2010
    ..In conclusion, the combination of MAPK and PI3K inhibitors represents a promising strategy to overcome endocrine therapy resistance in ER+ breast cancer patients...
  83. ncbi Reactive oxygen species, antioxidants, and the mammalian thioredoxin system
    J Nordberg
    Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
    Free Radic Biol Med 31:1287-312. 2001
    ..Dinitrohalobenzenes constitute a unique class of immunostimulatory TrxR inhibitors and we consider the immunomodulatory effects of dinitrohalobenzene compounds in view of their reactions with the Trx system...
  84. ncbi HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitination
    C Boyault
    INSERM, U823, Equipe Epigénétique et Signalisation Cellulaire, Institut Albert Bonniot, Universite Joseph Fourier, Domaine de la Merci, Grenoble, La Tronche Cedex, France
    Oncogene 26:5468-76. 2007
    ....
  85. ncbi Chromatin-modifying agents permit human hematopoietic stem cells to undergo multiple cell divisions while retaining their repopulating potential
    Hiroto Araki
    Section of Hematology Oncology, Department of Medicine, University of Illinois at Chicago, 909 S Wolcott Avenue, Chicago, IL 60612, USA
    Blood 109:3570-8. 2007
    ..These data indicate that HSC treated with chromatin-modifying agents are capable of undergoing repeated cell divisions in vitro while retaining their marrow-repopulating potential...
  86. pmc Dichloroacetate induces apoptosis and cell-cycle arrest in colorectal cancer cells
    B M Madhok
    Section of Translational Anaesthesia and Surgery, University of Leeds, Level 7 Clinical Sciences Building, St James s University Hospital, Leeds, UK
    Br J Cancer 102:1746-52. 2010
    ..Our aim was to determine if switching metabolism from glycolysis towards mitochondrial respiration would reduce growth preferentially in colorectal cancer cells over normal cells, and to examine the underlying mechanisms...
  87. ncbi Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma
    Qin C Ryan
    Clinical Trials Unit, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA
    J Clin Oncol 23:3912-22. 2005
    ..The objective of this study was to define the maximum-tolerated dose (MTD), the recommended phase II dose, the dose-limiting toxicity, and determine the pharmacokinetic (PK) and pharmacodynamic profiles of MS-275...
  88. ncbi Natural products as alpha-amylase and alpha-glucosidase inhibitors and their hypoglycaemic potential in the treatment of diabetes: an update
    R Tundis
    Department of Pharmaceutical Sciences, Faculty of Pharmacy, Nutrition and Health Sciences, University of Calabria, 87036 I Rende CS, Italy
    Mini Rev Med Chem 10:315-31. 2010
    ..This article reviews recent data on plant extracts and isolated natural compounds that are being tested for their hypglycaemic activity, highlights ongoing research and considers the future persepctives...
  89. ncbi Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1
    S A Caldwell
    Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA
    Oncogene 29:2831-42. 2010
    ..These findings identify O-GlcNAc as a novel mechanism through which alterations in glucose metabolism regulate cancer growth and invasion and suggest that OGT may represent novel therapeutic targets for breast cancer...
  90. ncbi Discovery and evaluation of inhibitors of human sphingosine kinase
    Kevin J French
    Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA
    Cancer Res 63:5962-9. 2003
    ..These compounds are the first examples of nonlipid inhibitors of SK with in vivo antitumor activity and so provide leads for additional development of inhibitors of this important molecular target...
  91. ncbi Design, synthesis, and structure-activity relationships of alkylcarbamic acid aryl esters, a new class of fatty acid amide hydrolase inhibitors
    Giorgio Tarzia
    Istituto di Chimica Farmaceutica e Tossicologica, Universita degli Studi di Urbino Carlo Bo, Piazza del Rinascimento 6, Italy
    J Med Chem 46:2352-60. 2003
    ..URB524 (N-cyclohexylcarbamic acid biphenyl-3-yl ester, 9g) is the most potent compound of the series (IC(50) = 63 nM) and was therefore selected for further optimization...
  92. pmc Targeting mitochondrial glutaminase activity inhibits oncogenic transformation
    Jian Bin Wang
    Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA
    Cancer Cell 18:207-19. 2010
    ..These findings highlight a previously unappreciated connection between Rho GTPase activation and cellular metabolism and demonstrate that targeting glutaminase activity can inhibit oncogenic transformation...
  93. ncbi Growth inhibition of human malignant glioma cells induced by the PI3-K-specific inhibitor
    Takashi Shingu
    Department of Biochemistry and Neurosurgery, Shimane Medical University, Izumo, Japan
    J Neurosurg 98:154-61. 2003
    ..The authors examined the effects of the PI3-K inhibitor 2-(4-morpholinyl)-8-phenylchromone (LY294002) on human malignant glioma cells, and compared these effects on PTEN-deficient cells with those on PTEN-wild-type (PTEN-wt) cells...
  94. doi Antizyme and antizyme inhibitor, a regulatory tango
    Chaim Kahana
    Department of Molecular Genetics, The Weizmann Institute of Science, 76100 Rehovot, Israel
    Cell Mol Life Sci 66:2479-88. 2009
    ....
  95. ncbi Characterization of the fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester (URB597): effects on anandamide and oleoylethanolamide deactivation
    Darren Fegley
    Department of Pharmacology, University of California, Irvine CA 92697 4625, USA
    J Pharmacol Exp Ther 313:352-8. 2005
    ..The results also suggest that an enzyme distinct from FAAH catalyzes OEA hydrolysis in the duodenum, where this lipid substance acts as a local satiety factor...
  96. ncbi Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5
    J A Bibb
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
    Nature 410:376-80. 2001
    ..Our results suggest that changes in Cdk5 levels mediated by DeltaFosB, and resulting alterations in signalling involving D1 dopamine receptors, contribute to adaptive changes in the brain related to cocaine addiction...
  97. doi Blockade of glucocorticoid excess at the tissue level: inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 as a therapy for type 2 diabetes
    Christopher Fotsch
    Department of Medicinal Chemistry, Amgen Inc, Thousand Oaks, California 91320, USA
    J Med Chem 51:4851-7. 2008
  98. ncbi Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivo
    Matthias Selbach
    Max Planck Institut für Infektionsbiologie, Abt Molekulare Biologie, Schumannstrasse 20 21, D 10117 Berlin, Germany
    J Biol Chem 277:6775-8. 2002
    ....
  99. ncbi Induction of the mitochondrial permeability transition mediates the killing of HeLa cells by staurosporine
    M Tafani
    Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Cancer Res 61:2459-66. 2001
    ..Phosphorylation of Bad prevents Bax translocation. Caspases participate in the events related to cell killing that occur subsequent to induction of the MPT...
  100. ncbi Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
    J S Steffan
    Department of Psychiatry and Human Behavior, Gillespie 2121, University of California, Irvine, California 92697, USA
    Nature 413:739-43. 2001
    ..These findings raise the possibility that therapy with HDAC inhibitors may slow or prevent the progressive neurodegeneration seen in Huntington's disease and other polyglutamine-repeat diseases, even after the onset of symptoms...
  101. pmc Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors
    Stanley F Barnett
    Department of Cancer Research, Merck and Company, Sumneytown Pike, West Point, PA 19454, USA
    Biochem J 385:399-408. 2005
    ....

Research Grants76

  1. Discovery metabolite profiling of the prolyl peptidases
    Alan Saghatelian; Fiscal Year: 2009
    ..Furthermore, the application of DMP to peptidases will demonstrate the generality of this approach for the future characterization of medically relevant enzymes and signaling pathways. ..
  2. BIOLOGICAL METAL CLUSTERS--BIOPHYSICAL & MODEL STUDIES
    Michael Maroney; Fiscal Year: 1992
    ..will provide a detailed understanding of biological processes and will aid in the design of pharmaceutical enzyme inhibitors and catalysts for various reactions...
  3. ACTIVE SITE OF HIV-1 REVERSE TRANSCRIPTASE
    Robert Evans; Fiscal Year: 1993
    ..The basis of the rational design of specific enzyme inhibitors is a knowledge of the structure and catalytic mechanism of an enzyme...
  4. An Aldosterone-Endothelin Feedback Mechanism on Sodium Homeostasis
    CHARLES WINGO; Fiscal Year: 2009
    ..This study will examine whether endothelin acts as a local inhibitory mechanism and feedback control system on the action of aldosterone. ..
  5. An Aldosterone-Endothelin Feedback Mechanism on Sodium Homeostasis
    CHARLES S contact WINGO; Fiscal Year: 2010
    ..This study will examine whether endothelin acts as a local inhibitory mechanism and feedback control system on the action of aldosterone. ..
  6. Nanoliter Lab-on-a-chip for Protein Crystallization
    Vamsee Pamula; Fiscal Year: 2007
    ..Recent antiviral drugs against AIDS are enzyme inhibitors, and their design was based on the detailed protein-drug interactions provided by crystal structures of the ..
  7. Nanoliter Lab-on-a-chip for Protein Crystallization
    Vamsee Pamula; Fiscal Year: 2006
    ..Recent antiviral drugs against AIDS are enzyme inhibitors, and their design was based on the detailed protein-drug interactions provided by crystal structures of the ..
  8. OVULATION--STUDIES USING IN VITRO PERFUSED OVARIES
    Edward Wallach; Fiscal Year: 1992
    ..rupture will be explored in vivo and in vitro using specific plasminogen activators (streptokinase, tPA) and enzyme inhibitors (tAMCHA, epsilon-amino caproic acid, aprotinin, and alpha 2-macroglobulin) as well as prostaglandins (PGF2 ..
  9. OVULATION--STUDIES USING IN VITRO PERFUSED OVARIES
    Edward Wallach; Fiscal Year: 1990
    ..rupture will be explored in vivo and in vitro using specific plasminogen activators (streptokinase, tPA) and enzyme inhibitors (tAMCHA, epsilon-amino caproic acid, aprotinin, and alpha 2-macroglobulin) as well as prostaglandins (PGF2 ..
  10. Mechanism of Arsenic-Induced Diabetes
    Miroslav Styblo; Fiscal Year: 2001
    ..have shown that trivalent methylated metabolites (Mas-III and DMAs-III) are more potent cytotoxins and enzyme inhibitors than iAs-III...
  11. Mechanism of Arsenic-Induced Diabetes
    Miroslav Styblo; Fiscal Year: 2002
    ..have shown that trivalent methylated metabolites (Mas-III and DMAs-III) are more potent cytotoxins and enzyme inhibitors than iAs-III...
  12. Improving Outcomes in Diabetic Nephropathy
    Robert Toto; Fiscal Year: 2002
    ..to ESRD despite inhibition of the renin-angiotensin-aldosterone system with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs)...
  13. Improving Outcomes in Diabetic Nephropathy
    Robert Toto; Fiscal Year: 2003
    ..to ESRD despite inhibition of the renin-angiotensin-aldosterone system with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs)...
  14. HE3 MR Diffusion & Low Dose CT Quantitation of Emphysema
    David Gierada; Fiscal Year: 2003
    ..proteinases in the pathogenesis of COPD is leading to searches for newer anti-inflammatory strategies and enzyme inhibitors. Though in the early stages of development, some of these new approaches may eventually provide therapy that ..
  15. HE3 MR Diffusion & Low Dose CT Quantitation of Emphysema
    David Gierada; Fiscal Year: 2005
    ..proteinases in the pathogenesis of COPD is leading to searches for newer anti-inflammatory strategies and enzyme inhibitors. Though in the early stages of development, some of these new approaches may eventually provide therapy that ..
  16. HE3 MR Diffusion & Low Dose CT Quantitation of Emphysema
    David Gierada; Fiscal Year: 2004
    ..proteinases in the pathogenesis of COPD is leading to searches for newer anti-inflammatory strategies and enzyme inhibitors. Though in the early stages of development, some of these new approaches may eventually provide therapy that ..
  17. HE3 MR Diffusion & Low Dose CT Quantitation of Emphysema
    David Gierada; Fiscal Year: 2002
    ..proteinases in the pathogenesis of COPD is leading to searches for newer anti-inflammatory strategies and enzyme inhibitors. Though in the early stages of development, some of these new approaches may eventually provide therapy that ..
  18. Pharmacogenetics and Cardiovascular Events
    Bruce Psaty; Fiscal Year: 2006
    ..products of these genes represent the sites of action for many cardiovascular drugs: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, all classes of diuretics, alpha blockers, beta-blockers, central alpha ..
  19. Pharmacogenetics and Cardiovascular Events
    Bruce Psaty; Fiscal Year: 2004
    ..products of these genes represent the sites of action for many cardiovascular drugs: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, all classes of diuretics, alpha blockers, beta-blockers, central alpha ..
  20. Pharmacogenetics and Cardiovascular Events
    Bruce Psaty; Fiscal Year: 2005
    ..products of these genes represent the sites of action for many cardiovascular drugs: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, all classes of diuretics, alpha blockers, beta-blockers, central alpha ..
  21. Pharmacogenetics and Cardiovascular Events
    Bruce Psaty; Fiscal Year: 2003
    ..products of these genes represent the sites of action for many cardiovascular drugs: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, all classes of diuretics, alpha blockers, beta-blockers, central alpha ..
  22. Phase III Trial of Minocycline in ALS:I-Clinical Center
    Paul Gordon; Fiscal Year: 2006
    ..Caspase enzyme inhibitors and anti-inflammatory agents have been shown to slow progression in the ALS model (6,7,17,18)...
  23. Phase III Trial of Minocycline in ALS:I-Clinical Center
    Paul Gordon; Fiscal Year: 2004
    ..Caspase enzyme inhibitors and anti-inflammatory agents have been shown to slow progression in the ALS model (6,7,17,18)...
  24. Phase III Trial of Minocycline in ALS:I-Clinical Center
    Paul Gordon; Fiscal Year: 2003
    ..Caspase enzyme inhibitors and anti-inflammatory agents have been shown to slow progression in the ALS model (6,7,17,18)...
  25. Phase III Trial of Minocycline in ALS:I-Clinical Center
    Paul Gordon; Fiscal Year: 2007
    ..Caspase enzyme inhibitors and anti-inflammatory agents have been shown to slow progression in the ALS model (6,7,17,18)...
  26. REGULATION OF HEME OXYGENASE IN NEONATAL ANIMALS
    David Stevenson; Fiscal Year: 1999
    ..to address the regulation of HO transcription in culture and living animals in the presence and absence of enzyme inhibitors. This proposal contains three specific aims...
  27. Phase III Trial of Minocycline in ALS:I-Clinical Center
    Paul Gordon; Fiscal Year: 2005
    ..Caspase enzyme inhibitors and anti-inflammatory agents have been shown to slow progression in the ALS model (6,7,17,18)...
  28. REGULATION OF HEME OXYGENASE IN NEONATAL ANIMALS
    David Stevenson; Fiscal Year: 2001
    ..to address the regulation of HO transcription in culture and living animals in the presence and absence of enzyme inhibitors. This proposal contains three specific aims...
  29. REGULATION OF HEME OXYGENASE IN NEONATAL ANIMALS
    David Stevenson; Fiscal Year: 2000
    ..to address the regulation of HO transcription in culture and living animals in the presence and absence of enzyme inhibitors. This proposal contains three specific aims...
  30. KININS AS MEDIATORS OF HUMAN REACTIONS
    David Proud; Fiscal Year: 1990
    ..the pathophysiological role of kinins in rhinitis, we will perform studies using angiotensin converting enzyme inhibitors in an attempt to reduce kinin destruction and to determine if increases kinin levels are associated with an ..
  31. Identification of G6PD inhibitors for the development of novel antimalarial drugs
    Lars Bode; Fiscal Year: 2010
    ..AIM 2 then uses these proteins in already established high-throughput screening assays to identify enzyme inhibitors. Compounds active in the low micromolar to nanomolar concentration range will be subject to detailed kinetic ..
  32. Identification of G6PD inhibitors for the development of novel antimalarial drugs
    Lars Bode; Fiscal Year: 2009
    ..AIM 2 then uses these proteins in already established high-throughput screening assays to identify enzyme inhibitors. Compounds active in the low micromolar to nanomolar concentration range will be subject to detailed kinetic ..
  33. Flavoenzymes in Pyrimidine Metabolism
    Bruce A Palfey; Fiscal Year: 2010
    ..The results of these studies will facilitate the design of enzyme inhibitors, which may be developed into useful drug candidates...
  34. AGING AND IN VIVO VASCULAR RESPONSIVENESS IN MEN
    Terrence Blaschke; Fiscal Year: 1990
    ..g., beta-agonists, alpha-agonists, calcium channel blockers and angiotensin converting enzyme inhibitors) correlate with responses produced by systemic exposure to the same drug or drug class...
  35. Renin Angioensin Aldosterone System in Drub Abuse and HIV-associated Nephropathy
    Pravin C Singhal; Fiscal Year: 2010
    ..Our long term research goal is to develop strategies to slow down the progression as well as find a cure of this devastating kidney disease. ..
  36. Angiotensin II and diabetic retinopathy
    ALFONSO SCICLI; Fiscal Year: 2003
    Clinical trials suggest that Angiotensin Converting Enzyme inhibitors (ACEi) slow the progression of diabetic retinopathy...
  37. Angiotensin II and diabetic retinopathy
    ALFONSO SCICLI; Fiscal Year: 2006
    DESCRIPTION (provided by applicant): Clinical trials suggest that Angiotensin Converting Enzyme inhibitors (ACEi) slow the progression of diabetic retinopathy...
  38. A Family Partnership Intervention for Heart Failure
    Sandra Dunbar; Fiscal Year: 2005
    ..dietary sodium (24-hour urinary sodium), medication adherence to HF drugs including angiotensin converting enzyme inhibitors and diuretics (Medication Event Monitoring System), heart failure severity (brain natriuretic peptide levels)..
  39. A Family Partnership Intervention for Heart Failure
    Sandra Dunbar; Fiscal Year: 2009
    ..dietary sodium (24-hour urinary sodium), medication adherence to HF drugs including angiotensin converting enzyme inhibitors and diuretics (Medication Event Monitoring System), heart failure severity (brain natriuretic peptide levels)..
  40. A Family Partnership Intervention for Heart Failure
    Sandra Dunbar; Fiscal Year: 2004
    ..dietary sodium (24-hour urinary sodium), medication adherence to HF drugs including angiotensin converting enzyme inhibitors and diuretics (Medication Event Monitoring System), heart failure severity (brain natriuretic peptide levels)..
  41. A Family Partnership Intervention for Heart Failure
    Sandra Dunbar; Fiscal Year: 2006
    ..dietary sodium (24-hour urinary sodium), medication adherence to HF drugs including angiotensin converting enzyme inhibitors and diuretics (Medication Event Monitoring System), heart failure severity (brain natriuretic peptide levels)..
  42. A Family Partnership Intervention for Heart Failure
    Sandra Dunbar; Fiscal Year: 2007
    ..dietary sodium (24-hour urinary sodium), medication adherence to HF drugs including angiotensin converting enzyme inhibitors and diuretics (Medication Event Monitoring System), heart failure severity (brain natriuretic peptide levels)..
  43. SIDEROPHORES, ANALOGS & BIOCONJUGATES: SYNTHESIS & STUDY
    Marvin Miller; Fiscal Year: 1991
    ..binding components of siderophores and the proposed analogs and conjugates, which can be used as specific enzyme inhibitors, agents for deferration therapy due to iron overload (in thalassemia), inhibitors of lipid peroxidation from ..
  44. Phase III Trial of Minocycline in ALS:I-Clinical Center
    Paul Gordon; Fiscal Year: 2007
    ..Caspase enzyme inhibitors and anti-inflammatory agents have been shown to slow progression in the ALS model (6,7,17,18)...
  45. Optimized Hydride Generation Systems for Arsenic Specia*
    Miroslav Styblo; Fiscal Year: 2006
    ..arsenicals, unlike their pentavalent counterparts, are more potent than iAs as cytotoxins, genotoxins, enzyme inhibitors, and as modulators of major signal transduction pathways in human cells...
  46. Optimized Hydride Generation System for Arsenic Analysis
    Miroslav Styblo; Fiscal Year: 2004
    ..arsenicals, unlike their pentavalent counterparts, are more potent than iAs as cytotoxins, genotoxins, enzyme inhibitors, and as modulators of major signal transduction pathways in human cells...
  47. Optimized Hydride Generation Systems for Arsenic Specia*
    Miroslav Styblo; Fiscal Year: 2005
    ..arsenicals, unlike their pentavalent counterparts, are more potent than iAs as cytotoxins, genotoxins, enzyme inhibitors, and as modulators of major signal transduction pathways in human cells...
  48. Amidoglycosylation Reactions of Glycal Metallanitrenes
    Christian Rojas; Fiscal Year: 2007
    ..sugars, crucial molecular components and precursors in biological systems, including structural polymers, enzyme inhibitors, and cell-surface glycoproteins...
  49. Gene Discovery and Heparan Sulfate Biogenesis
    Jeffrey D Esko; Fiscal Year: 2010
    ..The HSPGs bind numerous growth factors, cytokines, extracellular matrix components, enzymes and enzyme inhibitors, and they act as receptors or coreceptors for cell signaling, cell attachment, and endocytosis...
  50. Ac-SDKP in target organ damage in hypertension
    Oscar Carretero; Fiscal Year: 2002
    ..Angiotensin-converting enzyme inhibitors (ACEi) significantly reduce cardiovascular events, especially in high-risk patients...
  51. Optimization of pyrimidinyl prodrugs (PYPs) for malaria chemotherapy
    PRADIPSINH RATHOD; Fiscal Year: 2009
    ..PI has systematically considered multiple ways to attack malarial thymidylate synthase with nanomolar-level enzyme inhibitors active in whole cell assays...
  52. DESIGN OF PROTEASE INHIBITORS
    Paul Bartlett; Fiscal Year: 1992
    The proposed research involves synthesis of a number of enzyme inhibitors, evaluation of their binding behavior, and correlation of this binding behavior with turnover of related substrates...
  53. Neurohormonal Blockade and Outcomes in Diastolic Heart Failure
    Ali Ahmed; Fiscal Year: 2009
    ..immediate goal is to study the long-term effects of three neurohormonal antagonists: angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), beta-blockers and aldosterone antagonists, in three propensity-matched ..
  54. Role and Relevance of Pept1 in Drug Absorption, Disposition, and Dynamics
    David E Smith; Fiscal Year: 2012
    ..g., ?-lactam antibiotics, angiotensin-converting enzyme inhibitors, antiviral nucleoside prodrugs) and potentially toxic peptidomimetics (e.g., 5-aminolevulinic acid)...
  55. Role and Relevance of Pept1 in Drug Absorption, Disposition, and Dynamics
    David E Smith; Fiscal Year: 2010
    ..g., ?-lactam antibiotics, angiotensin-converting enzyme inhibitors, antiviral nucleoside prodrugs) and potentially toxic peptidomimetics (e.g., 5-aminolevulinic acid)...
  56. EFFECTS OF DIFFERENTIAL COST SHARING IN THE ELDERLY
    Stephen Soumerai; Fiscal Year: 1999
    ..series, will assess the impact of DCS for blood pressure lower drugs, specifically angiotensin converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB), on drug utilization and drug switching in elderly recipients of ..
  57. Clinical Impact of Bradykinin Receptor Polymorphisms
    James Gainer; Fiscal Year: 2004
    ..a B2 receptor dependent-mechanism, is an integral contributor to the efficacy of angiotensin converting enzyme inhibitors. Animal studies suggest that genetic variation altering the regulation or function of the B2 receptor has ..
  58. Clinical Impact of Bradykinin Receptor Polymorphisms
    James Gainer; Fiscal Year: 2002
    ..a B2 receptor dependent-mechanism, is an integral contributor to the efficacy of angiotensin converting enzyme inhibitors. Animal studies suggest that genetic variation altering the regulation or function of the B2 receptor has ..
  59. Clinical Impact of Bradykinin Receptor Polymorphisms
    James Gainer; Fiscal Year: 2005
    ..a B2 receptor dependent-mechanism, is an integral contributor to the efficacy of angiotensin converting enzyme inhibitors. Animal studies suggest that genetic variation altering the regulation or function of the B2 receptor has ..
  60. Clinical Impact of Bradykinin Receptor Polymorphisms
    James Gainer; Fiscal Year: 2003
    ..a B2 receptor dependent-mechanism, is an integral contributor to the efficacy of angiotensin converting enzyme inhibitors. Animal studies suggest that genetic variation altering the regulation or function of the B2 receptor has ..
  61. Predictive QSAR Modeling of HIV-1 Integrase Inhibitors
    Rajni Garg; Fiscal Year: 2009
    ..of HIV-1 infection mainly consists of the use of combinations of HIV-1 reverse transcriptase and protease enzyme inhibitors. However, numerous side effects and rapid emergence of drug resistant variants greatly limit their use in ..
  62. ACE Inhibition and Novel Cardiovascular Risk Factors
    Marco Pahor; Fiscal Year: 2002
    Angiotensin converting enzyme inhibitors (ACE inhibitors) may prevent cardiovascular events in high risk persons and improve skeletal muscle function in heart failure patients by means of mechanisms that are independent of blood pressure ..
  63. PHOSPHORUS-CONTAINING TRANSITION STATE ANALOGS
    Paul Bartlett; Fiscal Year: 1990
    The proposed research involves synthesis of a number of enzyme inhibitors, evaluation of their binding behavior, and correlation of this binding behavior with turnover of related substrates...
  64. ACE Inhibition and Novel Cardiovascular Risk Factors
    Marco Pahor; Fiscal Year: 2004
    Angiotensin converting enzyme inhibitors (ACE inhibitors) may prevent cardiovascular events in high risk persons and improve skeletal muscle function in heart failure patients by means of mechanisms that are independent of blood pressure ..
  65. ACE Inhibition and Novel Cardiovascular Risk Factors
    Marco Pahor; Fiscal Year: 2003
    Angiotensin converting enzyme inhibitors (ACE inhibitors) may prevent cardiovascular events in high risk persons and improve skeletal muscle function in heart failure patients by means of mechanisms that are independent of blood pressure ..
  66. HYDROGEN PEROXIDE TOXICITY TO BRAIN TUMORS
    Brian Ross; Fiscal Year: 1993
    ..Furthermore, we will use specific enzyme inhibitors to systematically investigate the role of enzymatic antioxidant systems used in the cellular detoxification ..
  67. ACE Inhibition and Novel Cardiovascular Risk Factors
    Marco Pahor; Fiscal Year: 2004
    Angiotensin converting enzyme inhibitors (ACE inhibitors) may prevent cardiovascular events in high risk persons and improve skeletal muscle function in heart failure patients by means of mechanisms that are independent of blood pressure ..