enzyme inhibitors


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 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
  3. 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
  4. 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
  5. 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
  6. pmc PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways
    Minli Wang
    University of Duisburg Essen, Medical School, Institute of Medical Radiation Biology, Hufeland Street 55, 45122 Essen, Germany
    Nucleic Acids Res 34:6170-82. 2006
  7. 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
  8. 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
  9. pmc Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1
    M Saitoh
    Department of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170, Japan
    EMBO J 17:2596-606. 1998
  10. ncbi Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension
    M Uehata
    Discovery Research Tokyo, Yoshitomi Pharmaceutical Industries Ltd, Saitama, Japan
    Nature 389:990-4. 1997

Detail Information

Publications343 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 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...
  3. 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
  4. 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...
  5. 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...
  6. pmc PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways
    Minli Wang
    University of Duisburg Essen, Medical School, Institute of Medical Radiation Biology, Hufeland Street 55, 45122 Essen, Germany
    Nucleic Acids Res 34:6170-82. 2006
    ..This form of DSB repair is sensitive to PARP-1 inhibitors. The results define the function of PARP-1 in DSB repair and characterize a candidate pathway responsible for joining errors causing genomic instability and cancer...
  7. 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
  8. 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...
  9. pmc Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1
    M Saitoh
    Department of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170, Japan
    EMBO J 17:2596-606. 1998
    ..The evidence that Trx is a negative regulator of ASK1 suggests possible mechanisms for redox regulation of the apoptosis signal transduction pathway as well as the effects of antioxidants against cytokine- and stress-induced apoptosis...
  10. ncbi Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension
    M Uehata
    Discovery Research Tokyo, Yoshitomi Pharmaceutical Industries Ltd, Saitama, Japan
    Nature 389:990-4. 1997
    ..Our findings indicate that p160ROCK-mediated Ca2+ sensitization is involved in the pathophysiology of hypertension and suggest that compounds that inhibit this process might be useful therapeutically...
  11. 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...
  12. ncbi Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors
    Nagma Khan
    TopoTarget UK LTD, 87a Milton Park, Abingdon, Oxon, OX14 4RY, UK
    Biochem J 409:581-9. 2008
  13. 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)...
  14. ncbi The therapeutic potential of poly(ADP-ribose) polymerase inhibitors
    Laszlo Virag
    Inotek Pharmaceutical Corp, Beverly, Massachusetts 01915, USA
    Pharmacol Rev 54:375-429. 2002
    ..Moreover, we discuss the potential use of PARP inhibitors as anticancer agents, radiosensitizers, and antiviral agents...
  15. ncbi The IKK NF-kappa B system: a treasure trove for drug development
    Michael Karin
    Laboratory of Gene Regulation and Signal Transduction Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0636, USA
    Nat Rev Drug Discov 3:17-26. 2004
  16. 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...
  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. 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...
  19. pmc Three decades of beta-lactamase inhibitors
    Sarah M Drawz
    Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
    Clin Microbiol Rev 23:160-201. 2010
    ..The goal for the next 3 decades will be to design inhibitors that will be effective for more than a single class of beta-lactamases...
  20. ncbi The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse
    G P Lim
    Departments of Medicine and Neurology, University of California, Los Angeles, Los Angeles, California 90095, USA
    J Neurosci 21:8370-7. 2001
    ..Microgliosis was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component shows promise for the prevention of Alzheimer's disease...
  21. 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...
  22. 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...
  23. 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...
  24. 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...
  25. 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...
  26. ncbi Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase
    Stefan Kubicek
    Research Institute of Molecular Pathology, Vienna Biocenter, Dr Bohrgasse 7, A 1030 Vienna, Austria
    Mol Cell 25:473-81. 2007
    ..Our data identify a biologically active HMTase inhibitor that allows for the transient modulation of H3K9me2 marks in mammalian chromatin...
  27. 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%)...
  28. 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...
  29. 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...
  30. 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...
  31. 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
  32. pmc The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2
    Oliver H Kramer
    Georg Speyer Haus, Paul Ehrlich Strasse 42 44, D 60596 Frankfurt, Germany
    EMBO J 22:3411-20. 2003
    ..Thus, poly-ubiquitination and proteasomal degradation provide an isoenzyme-selective mechanism for downregulation of HDAC2...
  33. 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...
  34. pmc Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease
    Emma Hockly
    Medical and Molecular Genetics, Guy s, King s and St Thomas School of Medicine, King s College London, Eighth Floor Guy s Tower, Guy s Hospital, London SE1 9RT, United Kingdom
    Proc Natl Acad Sci U S A 100:2041-6. 2003
    ..SAHA dramatically improved the motor impairment in R6/2 mice, clearly validating the pursuit of this class of compounds as HD therapeutics...
  35. 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...
  36. 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...
  37. 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...
  38. 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...
  39. 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...
  40. 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...
  41. 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...
  42. ncbi Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade
    S Pleschka
    , , , D-35392 Giessen, Germany
    Nat Cell Biol 3:301-5. 2001
    ..Thus, signalling through the mitogenic cascade seems to be essential for virus production and RNP export from the nucleus during the viral life cycle...
  43. ncbi Histone-deacetylase inhibitors: novel drugs for the treatment of cancer
    Ricky W Johnstone
    Cancer Immunology Program, Peter MacCallum Cancer Institute, Trescowthick Research Laboratories, Smorgon Family Building, St Andrews Place, East Melbourne, 3002 Victoria, Australia
    Nat Rev Drug Discov 1:287-99. 2002
    ..The remarkable tumour specificity of these compounds, and their potency in vitro and in vivo, underscore the potential of HDAC inhibitors as exciting new agents for the treatment of cancer...
  44. ncbi Telomerase and cancer therapeutics
    Calvin B Harley
    Geron Corporation, 230 Constitution Drive, Menlo Park, California 94025, USA
    Nat Rev Cancer 8:167-79. 2008
    ..The prospect of adding telomerase-based therapies to the growing list of new anticancer products is promising, but what are the advantages and limitations of different approaches, and which patients are the most likely to respond?..
  45. ncbi To cycle or not to cycle: a critical decision in cancer
    M Malumbres
    Molecular Oncology Program, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain
    Nat Rev Cancer 1:222-31. 2001
    ..Understanding the molecular mechanisms that underlie this commitment should provide important insights into how normal cells become tumorigenic and how new anticancer strategies can be devised...
  46. ncbi Tankyrase, a poly(ADP-ribose) polymerase at human telomeres
    S Smith
    The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Science 282:1484-7. 1998
    ..ADP-ribosylation of TRF1 diminished its ability to bind to telomeric DNA in vitro, suggesting that telomere function in human cells is regulated by poly(ADP-ribosyl)ation...
  47. pmc The mechanism of topoisomerase I poisoning by a camptothecin analog
    Bart L Staker
    deCODE Genetics, Incorporated, BioStructures Group, 7869 Northeast Day Road West, Bainbridge Island, WA 98110, USA
    Proc Natl Acad Sci U S A 99:15387-92. 2002
    ..The first class includes changes to residues that contribute to direct interactions with the drug, whereas a second class would alter interactions with the DNA and thereby destabilize the drug-binding site...
  48. 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...
  49. 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
  50. pmc Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage
    Jonathan M Solomon
    Elixir Pharmaceuticals, Inc, One Kendall Square, Cambridge, MA 02139, USA
    Mol Cell Biol 26:28-38. 2006
    ..These results show that, although SIRT1 deacetylates p53, this does not play a role in cell survival following DNA damage in certain cell lines and primary human mammary epithelial cells...
  51. pmc Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells
    Anand G Patel
    Department of Molecular Pharmacology and Experimental Therapeutics, Radiation Oncology, and Oncology, Mayo Clinic, Rochester, MN 55905, USA
    Proc Natl Acad Sci U S A 108:3406-11. 2011
  52. ncbi Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine
    Carlo Stresemann
    Division of Epigenetics, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany
    Int J Cancer 123:8-13. 2008
    ..We also discuss the mechanism of DNA methyltransferase inhibition and emphasize the need for the identification of predictive biomarkers for the further advancement of epigenetic therapies...
  53. ncbi 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...
  54. 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
  55. ncbi Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells
    B P Zhou
    Department of Molecular and Cellular Oncology, Breast Cancer Basic Research Program, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA
    Nat Cell Biol 3:245-52. 2001
    ..Our results indicate that HER-2/neu induces cytoplasmic localization of p21Cip1/WAF1 through activation of Akt to promote cell growth, which may have implications for the oncogenic activity of HER-2/neu and Akt...
  56. ncbi Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors
    Prakash Jagtap
    Inotek Pharmaceuticals Corp, Suite 419E, 100 Cummings Center, Beverly, Massachusetts 01915, USA
    Nat Rev Drug Discov 4:421-40. 2005
    ..This article presents an overview of the principal pathophysiological pathways and mechanisms that are governed by PARP, followed by the main structures and therapeutic actions of various classes of novel PARP inhibitors...
  57. ncbi Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1
    J A Le Good
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Science 281:2042-5. 1998
    ..The activation loop phosphorylation of PKCdelta in response to serum stimulation of cells was PI 3-kinase-dependent and was enhanced by PDK1 coexpression...
  58. 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...
  59. ncbi Discovery and development of SAHA as an anticancer agent
    P A Marks
    Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Oncogene 26:1351-6. 2007
    ..A new drug application has been approved for SAHA (vorinostat) treatment of cutaneous T-cell lymphoma...
  60. 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...
  61. 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...
  62. pmc N-myristoyltransferase inhibitors as new leads to treat sleeping sickness
    Julie A Frearson
    Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, UK
    Nature 464:728-32. 2010
    ..Our studies validate T. brucei N-myristoyltransferase as a promising therapeutic target for human African trypanosomiasis...
  63. ncbi Small-molecule inhibition of APT1 affects Ras localization and signaling
    Frank J Dekker
    Department of Chemical Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany
    Nat Chem Biol 6:449-56. 2010
    ..We identify APT1 as one of the thioesterases in the acylation cycle and show that this protein is a cellular target of the inhibitor...
  64. 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...
  65. 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...
  66. 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...
  67. 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...
  68. 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...
  69. 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...
  70. ncbi FK866, a highly specific noncompetitive inhibitor of nicotinamide phosphoribosyltransferase, represents a novel mechanism for induction of tumor cell apoptosis
    Max Hasmann
    Fujisawa GmbH, Neumarkter Strasse 61, 81673 Munich, Germany
    Cancer Res 63:7436-42. 2003
  71. 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...
  72. ncbi Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to deplete ATP
    Young H Ko
    The Russell H Morgan Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 2185, USA
    Biochem Biophys Res Commun 324:269-75. 2004
    ..In all 19 treated animals advanced cancers were eradicated without apparent toxicity or recurrence. These findings attest to the feasibility of completely destroying advanced, highly glycolytic cancers...
  73. ncbi Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis
    Ping Zhu
    Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe Branch, H v H Platz 1, D 76344 Eggenstein, Germany
    Cancer Cell 5:455-63. 2004
    ..Interference with HDAC2 by valproic acid largely diminishes adenoma formation in APC(min) mice. These findings point toward HDAC2 as a particularly relevant potential target in cancer therapy...
  74. ncbi Histone acetylation-independent effect of histone deacetylase inhibitors on Akt through the reshuffling of protein phosphatase 1 complexes
    Chang Shi Chen
    Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA
    J Biol Chem 280:38879-87. 2005
  75. 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
  76. ncbi Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future
    Y J Kim
    Center for Advanced Science and Innovation, Osaka University, Suita, Osaka, 565 0871, Japan
    Cell Mol Life Sci 62:1707-23. 2005
    ..This article overviews the various inhibitors obtained from natural and synthetic sources with their industrial importance...
  77. ncbi Mechanisms underlying endothelial dysfunction in diabetes mellitus
    U Hink
    Universitatskrankenhaus Eppendorf, Germany
    Circ Res 88:E14-22. 2001
    ..The full text of this article is available at http://www.circresaha.org...
  78. 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
  79. 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...
  80. 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...
  81. 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...
  82. 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...
  83. 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...
  84. 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...
  85. 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...
  86. 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...
  87. 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...
  88. 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...
  89. 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...
  90. 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...
  91. 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...
  92. 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
  93. 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...
  94. 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...
  95. 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...
  96. 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...
  97. ncbi 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...
  98. 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...
  99. 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
  100. 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
  101. 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...

Research Grants74

  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. Gene Therapy with Cardiotropic Vectors for the Treatment of Heart Failure
    Roger J Hajjar; Fiscal Year: 2013
    ..The impact of angiotensin converting enzyme inhibitors (ACEI) and b-blockers has translated into more sustained benefit, but many patients become intolerant to b-..
  3. Purkinje Origin of Ischemic Ventricular Tachycardia and Fibrillation
    James B Martins; Fiscal Year: 2013
    ..be pursued immediately in clinical trials since readily available drugs, statins or angiotensin converting enzyme inhibitors, may be combined for their oxidant and calcium/calmodulin kinase blocking effects to prevent sudden death in ..
  4. An Aldosterone-Endothelin Feedback Mechanism on Sodium Homeostasis
    Charles S Wingo; Fiscal Year: 2012
    ..Importantly, these studies will lend understanding into a novel signaling pathway that may explain the role of aldosterone in the progression of cardiovascular and renal disease. ..
  5. Pathogenic Mechanisms of PBEF in Ventilator Induced Lung Injury
    Joe G N Garcia; Fiscal Year: 2012
    ..We will assess the involvement of NamPT activity in homeostasis using enzyme inhibitors. In addition to providing novel therapeutic VILI strategies, these studies will yield novel mechanistic ..
  6. Steroid Regulation of Serotonin in Males
    CYNTHIA LOUISE BETHEA; Fiscal Year: 2013
    ..Aims 1 and 2 will establish groups of male macaques and manipulate the activity of ER2 and AR with enzyme inhibitors and a selective ER[unreadable] agonist, 8BV-E[unreadable] from Bayer-Schering...
  7. Comparative safety &effectiveness of antihypertensive medications in pregnancy
    BRIAN THOMAS BATEMAN; Fiscal Year: 2013
    ..We will also examine the safety of first trimester exposure to thiazide diuretics and angiotensin converting enzyme inhibitors, which are the most common types of antihypertensives used in women of reproductive age outside of pregnancy ..
  8. Inhibition of Carboxylesterase Metabolism by Ethanol
    Robert B Parker; Fiscal Year: 2011
    ..role in the metabolism and disposition of many clinically used medications including angiotensin-converting enzyme inhibitors, anticancer agents, statins, central nervous system stimulants, and drugs of abuse such as cocaine and ..
  9. Residual Kidney Function in ESRD: Measurements, Serum Markers and Outcomes
    Tariq Shafi; Fiscal Year: 2013
    ..randomized clinical trial to determine if RKF can be preserved by treatment with angiotensin converting enzyme inhibitors. The candidate for this mentored Career Development Award is an Instructor of Medicine in the Division of ..
  10. 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 ..
  11. Structural Studies of AIDS-Responsive Drugs
    Vivian Cody; Fiscal Year: 2010
    ..aim one focuses on cloning, expression, purification and crystallization of pjDHFR in complex with selected enzyme inhibitors. A baculovirusexpression system has been developed to produce soluble, stable enzyme and initial biochemical ..
  12. Broad-Spectrum Antimicrobials Targeting the D-Alanine Pathway
    KAREN G ANTHONY; Fiscal Year: 2013
    ..assay using recombinant Mycobacterium tuberculosis alanine racemase was developed to screen for novel enzyme inhibitors. A pilot screen identified promising 'hits'with antibacterial activity against M...
    Kenneth D Karlin; Fiscal Year: 2013
    ..Potential long-term applications of this basic research include development of enzyme inhibitors and relevant disease therapeutic strategies...
  14. Longitudinal Impact of Antihypertensive Polypharmacy on Geriatric Syndromes
    Joseph T Hanlon; Fiscal Year: 2012
    ..classes: 1) beta blockers;2) peripheral alpha blockers;3) calcium channel blockers;4) angiotensin converting enzyme inhibitors;5) angiotensin receptor blockers;6) direct vasodilators;7) diuretics and 8) central alpha blockers...
  15. Derivation of Mature Oocytes from Human Primordial Follicles
    AARON JW HSUEH; Fiscal Year: 2010
    ..The present application deals with the use of enzyme inhibitors and key ovarian growth factors to initiate the growth of dormant human ovarian follicles for subsequent ..
  16. Novel Aspects of the Cardiac Renin-Angiotensin System
    KENNETH MELVIN BAKER; Fiscal Year: 2012
    ..renin-angiotensin system, may provide substantial benefit for the prevention/treatment of diabetic cardiomyopathy, compared to standard therapy with angiotensin receptor blockers and angiotensin converting enzyme inhibitors.
  17. Low Thyroid function and myocardial infarction
    Anthony Martin Gerdes; Fiscal Year: 2013
    ..infarction (MI) has improved with the use of 2-adrenergic blockers (BB) and angiotensin converting enzyme inhibitors (ACEi)...
  18. Biologic Effects of Cdk2 Substrate Phosphorylation on Acute Kidney Injury
    Peter M Price; Fiscal Year: 2013
    ..We found that cell cycle enzyme inhibitors will totally protect kidney cells in vitro from cisplatin cytotoxicity and significantly diminish ..
  19. 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)..
  20. Associations among RAAS Inhibitors, Residual Kidney Function, and CV Events in PD
    Jenny I Shen; Fiscal Year: 2013
    ..provided by applicant): In patients with chronic kidney disease not on dialysis, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) slow the progression of diabetic nephropathy and reduce ..
  21. A novel strategy in antimicrobial drug discovery against Porphyromonas gingivalis
    VICTORIA NANETTE STONE; Fiscal Year: 2013
    ..a species-specific drug discovery strategy we propose the following aims: (1) to identify a set of potential enzyme inhibitors utilizing in silico molecular modeling, (2) to determine the efficacy of our candidate antimicrobial ..
  22. Improving Methods for Comparative Effectiveness Research in Cardiovascular Care
    SOKO SETOGUCHI-IWATA; Fiscal Year: 2012
    ..These proposed methods will be assessed using 4 clinically relevant CE questions: 1) angiotensin-converting enzyme inhibitors (ACEIs) vs. angiotensin II receptor blockers (ARBs) after myocardial infarction, 2) atorvastatin vs...
  23. Safety and Effectiveness Evaluations for Kidney Disease in Complex Patients
    DONALD READ MILLER; Fiscal Year: 2010
    ..within the following classes or groups of medications recommended for treating CKD: angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, and HMGcoA reductase inhibitors (statins)...
  24. Effect of Statin Therapy on Disease Progression in Children with ADPKD
    Robert W Schrier; Fiscal Year: 2012
    ..adults with autosomal dominant polycystic kidney disease (ADPKD) who are receiving angiotensin converting enzyme inhibitors. The primary endpoint of the study will be achieved in subjects with 20% or greater change over the three-..
    Feng Gai; Fiscal Year: 2013
    ..A molecular level knowledge of enzyme-inhibitors for HIV treatments and amyloid fibrils associated with Alzheimer's disease form another focus of this work. ..
  26. Quinoline-based Inhibitors of BoNT/A LC
    John D Williams; Fiscal Year: 2012
    ..BoNT/A metalloprotease by measuring the enzymatic and cellular activities, as well as the specificity of the enzyme inhibitors. We will correlate the in vitro activity of the compounds against BoNT/A LC with activity in a cellular ..
  27. RNA modification and antibiotic resistance
    GRAEME LESLIE CONN; Fiscal Year: 2013
    ..methyltransferase- small ribosome subunit recognition, which represents the best target for future specific enzyme inhibitors. We will determine critical amino acids within each enzyme for target specificity using site-directed ..
  28. 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...
  29. Biventricular Pacing in Heart Failure
    SAMIR FAWZI SABA; Fiscal Year: 2010
    ..York Heart Association Class III-IV) despite optimal pharmacologic therapy including angiotensin converting enzyme inhibitors, b-blockers, and potassium-sparing diuretics can extract benefits from BIV pacing in the form of improved ..
  30. Longitudinal Impact of Antihypertensive Polypharmacy on Geriatric Syndromes
    Joseph T Hanlon; Fiscal Year: 2010
    ..medication classes: 1) beta blockers;2) alpha blockers;3) calcium channel blockers;4) angiotensin converting enzyme inhibitors;5) angiotensin receptor blockers;6) direct vasodilators;and 7) diuretics)...
  31. Structure and Function of 3-O-sulfation in Heparan Sulfate
    Jeffrey D Esko; Fiscal Year: 2013
    ..sulfate binds many growth factors, chemokines, morphogens, extracellular matrix proteins, enzymes and enzyme inhibitors via relatively short sulfated saccharide sequences...
  32. Searching for Novel Genes in Heparan Sulfate Biosynthesis
    Emylie Seamen; Fiscal Year: 2013
    ..cell proliferation, including growth factors, morphogens, other extracellular matrix proteins, enzymes, and enzyme inhibitors. HSPGs have been implicated in cell growth and proliferation and tend to be mis-expressed in cancer cells ..
  33. Effects of ACE Inhibitor (ACEI) use on bone turnover in humans: a clinical trial
    NAHID JAMAL RIANON; Fiscal Year: 2013
    ..Antihypertensive medications affecting RAS, specifically angiotensin converting enzyme inhibitors (ACEI), decreased bone turnover in animals, and improved BMD in preliminary human studies...
  34. Substrate Activity Screening: A New Approach to Inhibitor Discovery
    Jonathan A Ellman; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Small molecule enzyme inhibitors serve as essential drugs for the treatment of a wide range of pervasive and life threatening diseases...
  35. Role and Relevance of Pept1 in Drug Absorption, Disposition, and Dynamics
    David E Smith; Fiscal Year: 2013
    ..g., ?-lactam antibiotics, angiotensin-converting enzyme inhibitors, antiviral nucleoside prodrugs) and potentially toxic peptidomimetics (e.g., 5-aminolevulinic acid)...
  36. Flavoenzymes in Pyrimidine Metabolism
    Bruce A Palfey; Fiscal Year: 2011
    ..The results of these studies will facilitate the design of enzyme inhibitors, which may be developed into useful drug candidates...
  37. Interactive Spaced Education to Optimize Diabetes Care
    B Price Kerfoot; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Randomized trials have clearly shown that angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) substantially reduce morbidity and mortality in patients with ..
  38. High-Throughput Small Molecule Screening Using Photonic Crystal Technology: Appli
    Brian T Cunningham; Fiscal Year: 2013
    ..Unfortunately, while enzyme inhibitors can be readily discovered through in vitro assays using chromogenic/fluorescent readouts, protein-DNA and ..
  39. Limited Competition: Clinical Centers for the HALT-Polycystic Kidney Disease Tria
    Arlene B Chapman; Fiscal Year: 2013
    ..These include Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blocking Agents (ARB)...
  40. Peptidomimetic Human SIRT1 Enzyme Inhibitors
    Weiping Zheng; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: The proposed project focuses on the development of the peptidomimetic human SIRT1 enzyme inhibitors. The proposed studies will help the development of novel anti-cancer therapeutics.
  41. Acquisition of 700 MHz NMR for Automated Chemical/Peptide Library Screening
    Dale F Mierke; Fiscal Year: 2010
    ..interactions in important signal transduction cascades, screening for competitive and allosteric enzyme inhibitors, and structural insight for rational modification of natural products...
  42. Renin Angioensin Aldosterone System in Drub Abuse and HIV-associated Nephropathy
    Pravin C Singhal; Fiscal Year: 2013
    ..Based on our preliminary data, we hypothesize that modulation of RAAS by its selective inhibitors will not only prevent or attenuate HIV-1- induced renal injury but also delay or slow down the progression of HIVAN. ..
  43. 20-HETE regulation of androgen-induced hypertension
    Cheng Chia Wu; Fiscal Year: 2012
    ..examine the contribution of each to 20-HETE-mediated male-specific hypertension using 1) pharmacological (enzyme inhibitors) and molecular/genetic (viral vectors and transgenic mouse models) to inhibit or induce the synthesis of 20-..
  44. Prospective meta-analyses of drug-gene interactions: CHARGE GWAS consortium
    Bruce M Psaty; Fiscal Year: 2013
    ..failure" among aspirin users), and use of non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics with renal function...
  45. Research Centers in Minority Institutions Clinical Rese*
    Eve Higginbotham; Fiscal Year: 2009
    ..IV. Define the efficacy of chronic treatment with angiotensin converting enzyme inhibitors as a means to improve endothelial function in African-American hypertensives with baseline endothelial ..
  46. Development of ACE Inhibitor as Countermeasure for Radiation-Induced Lung Injury
    MEETHA M MEDHORA; Fiscal Year: 2010
    ..Specifically we propose to accelerate development of FDA-approved Angiotensin Converting Enzyme inhibitors (ACEi), captopril, enalapril or fosinopril for safe and effective mitigation and treatment...
  47. Pharmaconeuropathology of Brain Aging and Dementia
    Joshua A Sonnen; Fiscal Year: 2013
    ..drugs with proposed neuroprotective actions (calcium channel blockers and angiotensin-converting enzyme inhibitors), and level of physical exercise...
  48. Endogenous Cannabinoids and Brain Function
    Aron H Lichtman; Fiscal Year: 2013
    ..approach involves synthesis of putative endocannabinoids, stable and potent analogs, metabolic and synthetic enzyme inhibitors and CB1 receptor allosteric modulators...
  49. The Alport Syndrome Symposium for Physicians, Researchers and Families
    Clifford E Kashtan; Fiscal Year: 2010
    ..interventions, including medications used routinely by nephrologists such as angiotensin converting enzyme inhibitors. Any intervention trial in Alport syndrome will require the active engagement and participation of Alport ..
  50. Human Folylpolyglutamate Synthetase and Cancer Therapeutics
    Richard G Moran; Fiscal Year: 2013
    ..When using antifolates in the treatment of cancer, the clinician is highjacking this mechanism to deliver enzyme inhibitors to the tumor cell and trap them there, in contact with their target for a substantial period of time...
  51. Improving management of cardiovascular medications during hospitalization
    Andrew D Auerbach; Fiscal Year: 2013
    ..medications (for example, use of aspirin in patients with coronary artery disease, or angiotensin-converting enzyme inhibitors in patients with congestive heart failure) are missed or dropped in noncardiac surgery patients, and how ..
  52. Pharmacepidemiology in the elderly: medications pneumonia risk and confounding
    Sascha Dublin; Fiscal Year: 2011
    ..between use of specific medications-acid-suppressing medications, benzodiazepines, angiotensin-converting enzyme inhibitors (ACEIs), and statins-and risk of pneumonia, a common and serious illness...
  53. Enantioselective Synthesis of Phosphinate Derivatives
    John Cong Gui Zhao; Fiscal Year: 2012
    ..They have very important biological activities, mainly as enzyme inhibitors. An enantioselective method is highly desirable for the medicinal chemistry and pharmaceutical industry, as ..
  54. Force field development for zinc metalloproteins
    Yingkai Zhang; Fiscal Year: 2012
    ..at developing novel transferable non-bonded force fields to model zinc metalloproteins and to design zinc enzyme inhibitors. Zinc proteins play essential roles in many biological processes, and there is an increasing appreciation of ..
  55. Computer Simulations of Enzymes
    Weitao Yang; Fiscal Year: 2012
    ..In addition, it will also serve to aid in the design of new drugs and enzyme inhibitors. PUBLIC HEALTH RELEVANCE: This proposal aims at developing methods for simulating chemical processes ..
  56. Computational Design of Inhibitor Specificity
    Bruce Tidor; Fiscal Year: 2012
    ..This project will pursue a new approach to the development of enzyme inhibitors that are less prone to the emergence of target resistance, namely the substrate envelope hypothesis, will ..
  57. Pathophysiological role of prorenin in CKD
    Alfred K Cheung; Fiscal Year: 2013
    ..Hence, angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) have been used extensively to treat these clinical disorders...
    John P Richard; Fiscal Year: 2012
    ..The focus of this application is the critical role of flexible phosphate gripper loops in enzymatic catalysis and the results may spur efforts to develop novel enzyme inhibitors that specifically target these loops.
  59. Complex Metallocluster Structure and Assembly
    Catherine L Drennan; Fiscal Year: 2012
    ..Our findings have applications for the synthesis of biomimetic catalysts and in the design of enzyme inhibitors. In addition to interrogating the mechanisms of metalloenzymes, it is important to investigate the cellular ..
  60. ACE Inhibition and Cardiac Allograft Vasculopathy
    William F Fearon; Fiscal Year: 2013
    ..Angiotensin converting enzyme inhibitors are used in less than one half of transplant recipients...
  61. 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 ..
    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 ..
  63. Rational Design of Adenylation Enzyme Inhibitors
    Derek S Tan; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Rational Design of Adenylation Enzyme Inhibitors Adenylation enzymes play central roles in diverse biological pathways across all three domains of life, mediating processes such as protein ..
  64. 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...
  65. 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 ..
  66. 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 ..
  67. 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...
  68. 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)...
  69. 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...
  70. 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 ..
    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 ..
  72. 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 ..
    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...
  74. 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 ..