maleimides

Summary

Top Publications

  1. pmc Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3
    Michael Martin
    Department of Oral Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294 2170, USA
    Nat Immunol 6:777-84. 2005
  2. ncbi Inhibition of GSK3beta by postconditioning is required to prevent opening of the mitochondrial permeability transition pore during reperfusion
    Ludovic Gomez
    INSERM U886, Universite Claude Bernard Lyon, 69373 Lyon, France
    Circulation 117:2761-8. 2008
  3. ncbi Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription
    M P Coghlan
    Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Essex, UK
    Chem Biol 7:793-803. 2000
  4. pmc Inhibition of GSK3 attenuates amphetamine-induced hyperactivity and sensitization in the mouse
    Nicole M Enman
    Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA
    Behav Brain Res 231:217-25. 2012
  5. ncbi Effect of oxybutynin and imidafenacin on central muscarinic receptor occupancy and cognitive function: a monkey PET study with [(11)C](+)3-MPB
    Shigeyuki Yamamoto
    Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm, Sweden
    Neuroimage 58:1-9. 2011
  6. ncbi Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif
    Albrecht Messerschmidt
    Department of Structural Research, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    J Mol Biol 352:918-31. 2005
  7. ncbi Activation of RhoA and inhibition of myosin phosphatase as important components in hypertension in vascular smooth muscle
    Tetsuya Seko
    First Department of Internal Medicine, Mie University School of Medicine, 2 174 Edobashi, Tsu, Mie 514 8507, Japan
    Circ Res 92:411-8. 2003
  8. ncbi Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy
    Lloyd Paul Aiello
    Beetham Eye Institute, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA
    Ophthalmology 113:2221-30. 2006
  9. pmc Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase
    Q Wang
    Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555 0536, USA
    Oncogene 25:43-50. 2006
  10. pmc Protein modification, bioconjugation, and disulfide bridging using bromomaleimides
    Mark E B Smith
    Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, UK
    J Am Chem Soc 132:1960-5. 2010

Research Grants

Detail Information

Publications245 found, 100 shown here

  1. pmc Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3
    Michael Martin
    Department of Oral Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294 2170, USA
    Nat Immunol 6:777-84. 2005
    ..These findings demonstrate a regulatory function for GSK3 in modulating the inflammatory response...
  2. ncbi Inhibition of GSK3beta by postconditioning is required to prevent opening of the mitochondrial permeability transition pore during reperfusion
    Ludovic Gomez
    INSERM U886, Universite Claude Bernard Lyon, 69373 Lyon, France
    Circulation 117:2761-8. 2008
    ..We investigated whether phosphorylated GSK3beta may protect the heart via the inhibition of mPTP opening during postconditioning...
  3. ncbi Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription
    M P Coghlan
    Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Essex, UK
    Chem Biol 7:793-803. 2000
    ..This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3...
  4. pmc Inhibition of GSK3 attenuates amphetamine-induced hyperactivity and sensitization in the mouse
    Nicole M Enman
    Department of Pharmacology and Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA, USA
    Behav Brain Res 231:217-25. 2012
    ..These data support a role for GSK3 in acute amphetamine-induced hyperactivity and the development of sensitization to amphetamine-induced stereotypy...
  5. ncbi Effect of oxybutynin and imidafenacin on central muscarinic receptor occupancy and cognitive function: a monkey PET study with [(11)C](+)3-MPB
    Shigeyuki Yamamoto
    Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm, Sweden
    Neuroimage 58:1-9. 2011
    ..30-40% in cortices and ca. 20-30% in brainstem, and a desirable drug for OAB treatment should not occupy central mAChR above these thresholds...
  6. ncbi Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif
    Albrecht Messerschmidt
    Department of Structural Research, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    J Mol Biol 352:918-31. 2005
    ..The PKCiota-BIM1 complex is the first kinase domain crystal structure of any atypical PKC and constitutes the basis for rational drug design for selective PKCiota inhibitors...
  7. ncbi Activation of RhoA and inhibition of myosin phosphatase as important components in hypertension in vascular smooth muscle
    Tetsuya Seko
    First Department of Internal Medicine, Mie University School of Medicine, 2 174 Edobashi, Tsu, Mie 514 8507, Japan
    Circ Res 92:411-8. 2003
    ..These results suggest that independent of the cause of hypertension, a common point in downstream signaling and a critical component of hypertension is activation of RhoA and subsequent activation of Rho-kinase...
  8. ncbi Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy
    Lloyd Paul Aiello
    Beetham Eye Institute, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA
    Ophthalmology 113:2221-30. 2006
    ..To evaluate the effect of ruboxistaurin, an orally administered protein kinase C beta (PKC beta) isozyme-selective inhibitor, on vision loss in patients with diabetes...
  9. pmc Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase
    Q Wang
    Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555 0536, USA
    Oncogene 25:43-50. 2006
    ..Importantly, our findings identify GSK-3, acting through PKCdelta, as a negative regulator of ERK1/2, thus revealing a novel crosstalk mechanism between these critical signaling pathways...
  10. pmc Protein modification, bioconjugation, and disulfide bridging using bromomaleimides
    Mark E B Smith
    Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ, UK
    J Am Chem Soc 132:1960-5. 2010
    ..These results highlight the significant potential for this new class of reagents in protein modification...
  11. pmc Inhibition of glycogen synthase kinase 3beta prevents peroxide-induced collapse of mitochondrial membrane potential in rat ventricular myocytes
    Karina Förster
    Department of Cardiology, Ernst Moritz Arndt University, Greifswald, Germany
    Clin Exp Pharmacol Physiol 37:684-8. 2010
    ..5. These experiments confirm that inhibition of GSK3 beta protects the myocytes, but also that the preconditioning mimetic DADLE loses its protective effect when a constitutively active GSK3 beta is present...
  12. ncbi Linking metabolism and immunology: diabetic nephropathy is an inflammatory disease
    Katherine R Tuttle
    J Am Soc Nephrol 16:1537-8. 2005
  13. ncbi Oral protein kinase c β inhibition using ruboxistaurin: efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with diabetic retinopathy in the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and the Protein Kinase C β Inhibit
    Lloyd Paul Aiello
    Joslin Diabetes Center, Beetham Eye Institute, Department of Ophthalmology, Harvard University Medical School, Boston, Massachusetts, USA
    Retina 31:2084-94. 2011
    ....
  14. ncbi Aqabamycins A-G: novel nitro maleimides from a marine Vibrio species. I. Taxonomy, fermentation, isolation and biological activities
    Wael Al-Zereini
    Institute for Biotechnology and Drug Research IBWF, Kaiserslautern, Germany
    J Antibiot (Tokyo) 63:297-301. 2010
    ..The aqabamycins, except aqabamycin A, bear a nitro group. Compounds 3, 4, 7 are described here for the first time from a natural source and vibrindole A was found to have cytotoxic activity...
  15. ncbi A PKC-beta inhibitor treatment reverses cardiac microvascular barrier dysfunction in diabetic rats
    Liping Wei
    Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi an, Shaanxi, China
    Microvasc Res 80:158-65. 2010
    ..PKC-beta inhibitor RBX prevented chronic cardiac microvascular barrier dysfunction and improved endothelial cell-cell junctional function in high glucose states...
  16. pmc Cocaine-induced hyperactivity and sensitization are dependent on GSK3
    Jonathan S Miller
    Department of Pharmacology and, Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA
    Neuropharmacology 56:1116-23. 2009
    ....
  17. pmc Nanosculpting reversed wavelength sensitivity into a photoswitchable iGluR
    Rika Numano
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    Proc Natl Acad Sci U S A 106:6814-9. 2009
    ..The ability to generate opposite responses with a single PTL and 2 versions of a target channel, which can be expressed in different cell types, paves the way for engineering opponency in neurons that mediate opposing functions...
  18. ncbi 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (SB216763), a glycogen synthase kinase-3 inhibitor, displays therapeutic properties in a mouse model of pulmonary inflammation and fibrosis
    Carmela Gurrieri
    Department of Clinical and Experimental Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy
    J Pharmacol Exp Ther 332:785-94. 2010
    ..These findings suggest that GSK-3 inhibition has a protective effect on lung fibrosis induced by BLM and candidate GSK-3 as a potential therapeutic target for preventing pulmonary fibrosis...
  19. ncbi The effect of ruboxistaurin on nephropathy in type 2 diabetes
    Katherine R Tuttle
    Research Department, The Heart Institute and Sacred Heart Medical Center, Spokane, WA 99204 2340, USA
    Diabetes Care 28:2686-90. 2005
    ..Ruboxistaurin selectively inhibits protein kinase C-beta and ameliorates kidney disease in animal models of diabetes. The purpose of this study was to evaluate the effects of ruboxistaurin on diabetic nephropathy in humans...
  20. ncbi Specificity of action of bisindolylmaleimide protein kinase C inhibitors: do they inhibit the 70kDa ribosomal S6 kinase in cardiac myocytes?
    Neil A Roberts
    Cardiovascular Division, King s College London, The Rayne Institute, St Thomas Hospital, London SE17EH, UK
    Biochem Pharmacol 68:1923-8. 2004
    ..We conclude that; (1) data obtained in vitro may not necessarily be extrapolated to intact cells and (2) inhibition of p70(S6K) is unlikely to contribute to the actions of GF109203X and Ro31-8220 in ARVM...
  21. ncbi Constitutive activation of GSK3 down-regulates glycogen synthase abundance and glycogen deposition in rat skeletal muscle cells
    Katrina MacAulay
    Division of Molecular Physiology, Medical Sciences Institute Wellcome Trust Building Complex, Faculty of Life Sciences, University of Dundee, DD1 5EH, United Kingdom
    J Biol Chem 280:9509-18. 2005
    ....
  22. pmc Pharmacological inhibition of GSK-3 in a guinea pig model of LPS-induced pulmonary inflammation: I. Effects on lung remodeling and pathology
    Hoeke A Baarsma
    Department of Molecular Pharmacology, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
    Respir Res 14:113. 2013
    ..The kinase acts as a negative regulator in β-catenin signalling and is critically involved in the smad pathway. Activation of both pathways may contribute to pulmonary features of chronic obstructive pulmonary disease (COPD)...
  23. ncbi In vitro and in vivo study of an albumin-binding prodrug of doxorubicin that is cleaved by cathepsin B
    Khalid Abu Ajaj
    Tumor Biology Center, Breisacher Strasse 117, 79106, Freiburg, Germany
    Cancer Chemother Pharmacol 64:413-8. 2009
    ....
  24. ncbi Development of methods for the synthesis of libraries of substituted maleimides and α,β-unsaturated-γ-butyrolactams
    Emelia Awuah
    Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada L8S 4M1
    J Org Chem 76:3122-30. 2011
    ..of Pd cross-coupling and conjugate addition/elimination reactions to permit the facile production of bisaryl-maleimides, anilinoaryl-maleimides, and bisanilino-maleimides while allowing control over the synthesis of symmetrical or ..
  25. pmc Mu and kappa opioid receptors activate ERK/MAPK via different protein kinase C isoforms and secondary messengers in astrocytes
    Mariana M Belcheva
    E A Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, Missouri 63104, USA
    J Biol Chem 280:27662-9. 2005
    ..Collectively, our findings on acute opioid effects suggest that differences in their mechanism of signaling may contribute to the distinct outcomes on ERK modulation induced by chronic mu and kappa opioids...
  26. pmc Catalysis of imido group hydrolysis in a maleimide conjugate
    Jeet Kalia
    Department of Biochemistry, University of Wisconsin Madison, 433 Babcock Drive, Madison, WI 53706, USA
    Bioorg Med Chem Lett 17:6286-9. 2007
    b>Maleimides are often used for biomolecular conjugation with thiols. An underappreciated aspect of the imido group in a maleimide conjugate is its susceptibility to spontaneous hydrolysis, resulting in undesirable heterogeneity...
  27. ncbi Inactivation of glycogen synthase kinase-3beta, a downstream target of the raf-1 pathway, is associated with growth suppression in medullary thyroid cancer cells
    Muthusamy Kunnimalaiyaan
    University of Wisconsin, H4 750 Clinical Science Center, 600 Highland Avenue, Madison, WI 53792, USA
    Mol Cancer Ther 6:1151-8. 2007
    ..Also, our results show that inactivation of GSK-3beta alone is sufficient to inhibit the growth of TT cells both in vitro and in vivo...
  28. ncbi Pharmacologic modulation of glycogen synthase kinase-3beta promotes p53-dependent apoptosis through a direct Bax-mediated mitochondrial pathway in colorectal cancer cells
    Jing Tan
    Laboratory of Molecular Pharmacology, Genome Institute of Singapore, Singapore, Singapore
    Cancer Res 65:9012-20. 2005
    ..Importantly, our data suggest that small-molecule inhibition of GSK-3beta might represent a novel approach for modulating chemotherapy...
  29. ncbi Protein kinase c increases the apparent affinity of the release machinery to Ca2+ by enhancing the release machinery downstream of the Ca2+ sensor
    X S Wu
    Departments of Anesthesiology and Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
    J Neurosci 21:7928-36. 2001
    ..These results have provided the first example of the mechanisms underlying modulation of the Prob(Ca)...
  30. pmc Lenticular mitoprotection. Part A: Monitoring mitochondrial depolarization with JC-1 and artifactual fluorescence by the glycogen synthase kinase-3β inhibitor, SB216763
    Morgan M Brooks
    Department of Cell Biology and Anatomy, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA
    Mol Vis 19:1406-12. 2013
    ..We demonstrate the novel use of spectral deconvolution to negate the interfering contributing fluorescence by SB216763, thus allowing an unfettered analysis of the JC-1 dye to determine the mitochondrial membrane potential...
  31. ncbi The P2X(7) receptor-mediated phospholipase D activation is regulated by both PKC-dependent and PKC-independent pathways in a rat brain-derived Type-2 astrocyte cell line, RBA-2
    Amos C Hung
    Institute of Neuroscience, College of Life Science, National Yang Ming University, No 155, Section 2, Li Non Street, Shi Pai, Taipei 112, Taiwan, ROC
    Cell Signal 14:83-92. 2002
    ..Additionally, CaMKII may participate in the PKC-dependent pathway, and tyrosine kinase may play a pivotal role on both PKC-dependent and PKC-independent pathways in the P2X(7)R-mediated PLD activation in RBA-2 cells...
  32. ncbi Targeting glycogen synthase kinase-3β to prevent hyperoxia-induced lung injury in neonatal rats
    Stefanie C Hummler
    Department of Pediatrics, Division of Neonatology, Batchelor Children s Research Institute, University of Miami Miller School of Medicine, Miami, FL 33101, USA
    Am J Respir Cell Mol Biol 48:578-88. 2013
    ..Thus, targeting GSK-3β signaling may offer a novel strategy to prevent and treat preterm infants with BPD...
  33. pmc In situ maleimide bridging of disulfides and a new approach to protein PEGylation
    Felix F Schumacher
    Department of Chemistry, University College London, 20 Gordon Street, London, WC1H OAJ, United Kingdom
    Bioconjug Chem 22:132-6. 2011
    ..This approach is then used to PEGylate the peptide hormone somatostatin and retention of biological activity is demonstrated...
  34. pmc Quality of life and objective measures of diabetic neuropathy in a prospective placebo-controlled trial of ruboxistaurin and topiramate
    Amanda Boyd
    Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, Virginia, USA
    J Diabetes Sci Technol 5:714-22. 2011
    ..We aimed to determine if the Norfolk QOL-DN could be used to capture changes in QOL that correlate with nerve fiber-specific objective measures in a placebo-controlled trial of two agents that affect different nerve fibers...
  35. ncbi Validation of reference tissue model of PET ligand [¹¹C]+3-MPB for the muscarinic cholinergic receptor in the living brain of conscious monkey
    Shigeyuki Yamamoto
    Osaka Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431 3192, Japan
    Synapse 65:548-51. 2011
    ..The present study suggests that the cerebellum is a suitable reference region for quantification of mAChR in the living brain with [¹¹C]+3-MPB and PET...
  36. ncbi Polymeric dibromomaleimides as extremely efficient disulfide bridging bioconjugation and pegylation agents
    Mathew W Jones
    Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK
    J Am Chem Soc 134:1847-52. 2012
    ..In addition, the tertiary structure of the peptide is efficiently maintained...
  37. pmc Tunable reagents for multi-functional bioconjugation: reversible or permanent chemical modification of proteins and peptides by control of maleimide hydrolysis
    Chris P Ryan
    Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK
    Chem Commun (Camb) 47:5452-4. 2011
    ..The application of this methodology to reversible protein biotinylation, the irreversible labeling of peptide disulfide bonds and the assembly of stable, fluorescein-labelled glycoprotein mimics is described...
  38. pmc Muscarinic receptor occupancy and cognitive impairment: a PET study with [11C](+)3-MPB and scopolamine in conscious monkeys
    Shigeyuki Yamamoto
    Osaka Hamamatsu Joint Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan
    Neuropsychopharmacology 36:1455-65. 2011
    ..These results indicate that a significant degree of mAChRs occupancy is needed to produce cognitive impairment by scopolamine. Furthermore, the importance of the brainstem cholinergic system in working memory in monkey is described...
  39. ncbi Synthesis and evaluation of peptidic maleimides as transglutaminase inhibitors
    Dany Halim
    Departement de Chimie, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Que, Canada H3C 3J7
    Bioorg Med Chem Lett 17:305-8. 2007
    ..These compounds were evaluated in vitro and shown to lead to irreversible inactivation of tissue transglutaminase. Comparison with inhibitors studied previously provides insight into the steric environment of the enzyme active site...
  40. pmc Inhibition of Bfl-1 with N-aryl maleimides
    John R Cashman
    Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, United States
    Bioorg Med Chem Lett 20:6560-4. 2010
    ..Inhibitors of Bfl-1 are potential development candidates for anti-cancer therapeutics...
  41. pmc Selective PKC beta inhibition with ruboxistaurin and endothelial function in type-2 diabetes mellitus
    Nehal N Mehta
    Cardiovascular Institute, University of Pennsylvania Medical Center, 909 BRB 2 3, 421 Curie Blvd, Philadelphia, PA 19104 6160, USA
    Cardiovasc Drugs Ther 23:17-24. 2009
    ..Prior studies demonstrate beneficial effects of PKC beta inhibition on microvascular parameters, but, to date, no study has examined the effect on macrovascular atherosclerotic readouts...
  42. ncbi Inhibition of glycogen synthase kinase-3 represses androgen receptor activity and prostate cancer cell growth
    Michal Mazor
    Prostate Cancer Research Group, Department of Cancer Cell Biology, Division of Medicine, Imperial College, London W12 0NN, UK
    Oncogene 23:7882-92. 2004
    ..Finally, inhibition of GSK-3 reduced the growth of AR-expressing prostate cancer cell lines. Our observations suggest a potential new therapeutic application for GSK-3 inhibitors in prostate cancer...
  43. pmc Inhibition of GSK3 attenuates dopamine D1 receptor agonist-induced hyperactivity in mice
    Jonathan S Miller
    Department of Pharmacology and the Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, United States
    Brain Res Bull 82:184-7. 2010
    ..Inhibition of GSK3 via SB 216763 dose-dependently reduced ambulatory and stereotypic activity produced by SKF-82958. These data implicate a role for GSK3 in the behavioral manifestations associated with dopamine D1 receptor activation...
  44. ncbi Glycogen synthase kinase-3 inhibitors protect central neurons against excitotoxicity
    Laura Facci
    Neurophysiology and Cell Sciences, GlaxoSmithKline Research and Development Ltd, Third Avenue, Harlow, Essex CM19 5AW, UK
    Neuroreport 14:1467-70. 2003
    ..As GSK-3 can modulate transcriptional events, these results may provide insight into the identification of new neuroprotective targets...
  45. ncbi Role of protein kinase C on the expression of platelet-derived growth factor and endothelin-1 in the retina of diabetic rats and cultured retinal capillary pericytes
    Tamotsu Yokota
    Research Division, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA
    Diabetes 52:838-45. 2003
    ..The novel demonstration of elevated expression of PDGF-B and its induction by PKC activation identifies a potential new molecular step in the pathogenesis of diabetic retinopathy...
  46. pmc Inhibition of glycogen synthase kinase-3 in androgen-responsive prostate cancer cell lines: are GSK inhibitors therapeutically useful?
    Ludwig Rinnab
    Department of Urology, University of Ulm, Ulm, Germany
    Neoplasia 10:624-34. 2008
    ..Although not all GSK inhibitors affected AR-stability/function, our observations suggest a potential new therapeutic application for some of these compounds in prostate cancer...
  47. ncbi Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death
    D A Cross
    Neurology Centre of Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, Harlow, Essex, UK
    J Neurochem 77:94-102. 2001
    ....
  48. pmc GSK-3 represses growth factor-inducible genes by inhibiting NF-kappaB in quiescent cells
    Julie R Graham
    Program in Molecular Biology, Cell Biology and Biochemistry, Boston University, Boston, Massachusetts 02215, USA
    J Biol Chem 285:4472-80. 2010
    ..This inhibition of NF-kappaB is consistent with the role of GSK-3 in the induction of apoptosis or cell cycle arrest in cells deprived of growth factors...
  49. ncbi Inhibition of protein kinase Cbeta protects against diabetes-induced impairment in arachidonic acid dilation of small coronary arteries
    Wei Zhou
    Department of Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
    J Pharmacol Exp Ther 319:199-207. 2006
    ..LY protects against these defects in diabetes through inhibition of PKCbeta-mediated production of ROS...
  50. ncbi Structure of the catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor
    Neil Grodsky
    Department of Structural and Computational Biology and Design, Pfizer Global Research and Development, Pfizer La Jolla Laboratories, 10777 Science Center Drive, San Diego, California 92121, USA
    Biochemistry 45:13970-81. 2006
    ..Given the pathogenic role of PKCbetaII in the development of diabetic complications, this structure can serve as a template for the rational design of inhibitors as potential therapeutic agents...
  51. pmc Efficacy of small-molecule glycogen synthase kinase-3 inhibitors in the postnatal rat model of tau hyperphosphorylation
    M L Selenica
    Division of Biological Research, H Lundbeck A S, Copenhagen, Denmark
    Br J Pharmacol 152:959-79. 2007
    ..Here, we assess five GSK-3beta inhibitors and lithium in lowering phosphorylated tau (p-tau) and GSK-3beta enzyme activity levels in 12-day old postnatal rats...
  52. ncbi Inhibition of protein kinase Cbeta prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans
    Joshua A Beckman
    Cardiovascular Division, Brigham and Women s Hospital, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02115, USA
    Circ Res 90:107-11. 2002
    ..These findings suggest that hyperglycemia impairs endothelial function, in part, via protein kinase Cbeta activation...
  53. ncbi GSK3 inhibitors show benefits in an Alzheimer's disease (AD) model of neurodegeneration but adverse effects in control animals
    Shuxin Hu
    Greater Los Angeles Healthcare System, Geriatric Research Education and Clinical Center, Veteran s Affairs Medical Center, USA
    Neurobiol Dis 33:193-206. 2009
    ..These data support a role for GSK3 hyperactivation in AD pathogenesis, but emphasize the importance of developing inhibitors that do not suppress constitutive activity...
  54. pmc Inhibition of protein kinase Cbeta does not improve endothelial function in type 2 diabetes
    Joshua A Beckman
    Brigham and Women s Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA
    J Clin Endocrinol Metab 95:3783-7. 2010
    ..Antagonism of protein kinase Cbeta (PKCbeta) restores endothelial function in experimental models of diabetes and prevents vascular dysfunction in response to hyperglycemia in healthy humans...
  55. ncbi Activation of P2X7 purinoceptor-stimulated TGF-beta 1 mRNA expression involves PKC/MAPK signalling pathway in a rat brain-derived type-2 astrocyte cell line, RBA-2
    Chia Mei Wang
    Institute of Neuroscience, College of Life Science, National Yang Ming University, Brain Research Center, University System of Taiwan, Taipei, Taiwan, ROC
    Cell Signal 15:1129-37. 2003
    ..In conclusion, activation of P2X(7) receptors enhanced TGF-beta 1 mRNA expression and the effect involved PKC/MAPK signalling pathway in RBA-2 type-2 astrocytes...
  56. pmc Inhibition of glycogen synthase kinase-3beta is sufficient for airway smooth muscle hypertrophy
    Huan Deng
    Department of Pediatrics and Communicable Diseases, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, MI 48109, USA
    J Biol Chem 283:10198-207. 2008
    ..On the other hand, TGF-beta-induced hypertrophy does not depend on GSK-3beta/eIF2B signaling...
  57. ncbi Inhibition of GSK3 differentially modulates NF-kappaB, CREB, AP-1 and beta-catenin signaling in hepatocytes, but fails to promote TNF-alpha-induced apoptosis
    Frank Götschel
    Institute of Molecular Medicine and Cell Research, University of Freiburg, Germany
    Exp Cell Res 314:1351-66. 2008
    ..These signaling molecules may compensate for the compromised anti-apoptotic function of NF-kappaB and allow survival of hepatocytes in the presence of TNF-alpha and GSK-3 inhibition...
  58. ncbi Glycogen synthase kinase-3 inhibitors prevent caspase-dependent apoptosis induced by ethanol in cultured rat cortical neurons
    Tsuneo Takadera
    Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa 920 1148, Japan
    Eur J Pharmacol 499:239-45. 2004
    ..These results suggest that ethanol induces caspase-dependent apoptosis mediated by glycogen synthase kinase-3 activation in cultured rat cortical neurons...
  59. ncbi Protein kinase C modulates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by targeting the apical events of death receptor signaling
    Nicholas Harper
    Medical Research Council Toxicology Unit, University of Leicester, Hodgkin Bldg, P O Box 138, Lancaster Rd, Leicester LE1 9HN, United Kingdom
    J Biol Chem 278:44338-47. 2003
    ....
  60. ncbi Synthesis and biological evaluation of novel 4-azaindolyl-indolyl-maleimides as glycogen synthase kinase-3beta (GSK-3beta) inhibitors
    Qing Ye
    ZJU ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
    Bioorg Med Chem 17:4302-12. 2009
    A series of novel 4-azaindolyl-indolyl-maleimides were synthesized and evaluated for their GSK-3beta inhibitory activity. Most compounds exhibited high potency to GSK-3beta...
  61. ncbi Aqabamycins A-G: novel nitro maleimides from a marine Vibrio species: II. Structure elucidation
    Clarisse Blandine Fotso Fondja Yao
    Institute for Organic and Biomolecular Chemistry, Georg August University Gottingen, Gottingen, Germany
    J Antibiot (Tokyo) 63:303-8. 2010
    ..Some of the known metabolites (for example, 3, 4 and 7) are described in this study for the first time as natural products. Their structures were elucidated based on 1D and 2D NMR, MS spectra and by comparison with synthetic material...
  62. ncbi Histamine-induced vasoconstriction involves phosphorylation of a specific inhibitor protein for myosin phosphatase by protein kinase C alpha and delta isoforms
    M Eto
    Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
    J Biol Chem 276:29072-8. 2001
    ..The results imply that histamine stimulation elicits contraction of vascular smooth muscle through activation of PKC alpha and especially PKC delta to phosphorylate CPI-17...
  63. ncbi A method for bioconjugation of carbohydrates using Diels-Alder cycloaddition
    Vince Pozsgay
    Laboratory of Developmental and Molecular Immunity, and Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 2720, USA
    Org Lett 4:3191-4. 2002
    ..The procedure described is the first for creating a carbon-carbon covalent bond in the bioconjugation step between a saccharide and a protein...
  64. ncbi The proinvasive activity of Wnt-2 is mediated through a noncanonical Wnt pathway coupled to GSK-3beta and c-Jun/AP-1 signaling
    Nathalie Le Floch
    INSERM U482, Signal Transduction and Cellular Functions in Diabetes and Digestive Cancers, Hopital Saint Antoine, Paris Cedex, France
    FASEB J 19:144-6. 2005
    ..Our data provide a potential clue for our understanding of the action and crosstalk between Wnt activators and other proinvasive pathways, in relation with matrix substrates and proteases in human cancers...
  65. ncbi A molecular study of pathways involved in the inhibition of cell proliferation in neuroblastoma B65 cells by the GSK-3 inhibitors lithium and SB-415286
    Javier G Pizarro
    Unitat de Farmacologia i Farmacognosia, Facultat de Farmacia, Institut de Biomedicina and Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain
    J Cell Mol Med 13:3906-17. 2009
    ..We conclude that inhibitors of GSK-3 induced cell-cycle arrest, mediated by the phosphorylation of cdc2 and, in the case of SB-415286, SIRT2 expression, which induced apoptosis in a caspase-independent manner...
  66. ncbi MP4, a new nonvasoactive PEG-Hb conjugate
    Kim D Vandegriff
    Sangart, Inc, 11189 Sorrento Valley Road, Suite 104, San Diego, CA 92121, USA
    Transfusion 43:509-16. 2003
    ..Vasoconstriction has been an obstacle to clinical development of Hb-based O2 carriers. It is proposed that this limitation can be overcome by increasing molecular size and oxygen affinity...
  67. ncbi Fluorescence spectroscopic analysis of the proximity changes between the central helix of troponin C and the C-terminus of troponin T from chicken skeletal muscle
    Ying Ming Liou
    Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan
    Biochim Biophys Acta 1774:466-73. 2007
    ..These results suggest that TnI plays an essential role in the Ca(2+) -mediated change in the spatial relationship between the C-lobe of TnC and the C-terminus of TnT...
  68. ncbi G-protein-dependent and -independent pathways regulate proteinase-activated receptor-2 mediated p65 NFkappaB serine 536 phosphorylation in human keratinocytes
    Fui Goon Goh
    Strathclyde Institute of Pharmacy and Biomedical Sciences, Division of Physiology and Pharmacology, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR, Scotland, UK
    Cell Signal 20:1267-74. 2008
    ..Overall these novel data demonstrate an IKK2-dependent, predominantly G-protein-independent pathway involved in PAR-2 regulation of NFkappaB phosphorylation in keratinocytes...
  69. pmc RhoA kinase and protein kinase C participate in regulation of rabbit stomach fundus smooth muscle contraction
    Paul H Ratz
    Department of Physiological Sciences, Eastern Virginia Medical School, PO Box 1980, Norfolk, Virginia, VA 23501, USA
    Br J Pharmacol 137:983-92. 2002
    ....
  70. ncbi Glucocorticoids and lithium reciprocally regulate the proliferation of adult dentate gyrus-derived neural precursor cells through GSK-3beta and beta-catenin/TCF pathway
    Shuken Boku
    Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
    Neuropsychopharmacology 34:805-15. 2009
    ..These results suggest that GSK-3beta and beta-catenin/TCF pathway might be important in the reciprocal effects between DEX and Li on ADP proliferation and are new targets of therapeutic agents for stress-related disorders...
  71. pmc Oxidation and haem loss kinetics of poly(ethylene glycol)-conjugated haemoglobin (MP4): dissociation between in vitro and in vivo oxidation rates
    Kim D Vandegriff
    Sangart, Inc, 6175 Lusk Blvd, San Diego, California 92121 USA
    Biochem J 399:463-71. 2006
    ....
  72. ncbi Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4)
    Dan Drobin
    Department of Anesthesiology, Karolinska Institute at Soder Hospital, S 118 83 Stockholm, Sweden
    J Appl Physiol 96:1843-53. 2004
    ....
  73. ncbi A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified Hemoglobin (Hemospan) in patients undergoing major orthopedic surgery
    Christina Olofsson
    Karolinska University Hospital, Solna, Stockholm, Sweden
    Anesthesiology 105:1153-63. 2006
    ..Because adverse events are expected to increase with age, the authors conducted a phase II safety study of Hemospan in elderly patients undergoing elective hip arthroplasty during spinal anesthesia...
  74. ncbi Toxicity and hemodynamic effects after single dose administration of MalPEG-hemoglobin (MP4) in rhesus monkeys
    Mark A Young
    Sangart, Inc, San Diego, CA 92121, USA
    Transl Res 149:333-42. 2007
    ..These results demonstrate that MP4 is safe and is without hemodynamic effects when administered as an exchange transfusion of 30% of estimated blood volume...
  75. ncbi Disposition of LY333531, a selective protein kinase C beta inhibitor, in the Fischer 344 rat and beagle dog
    J L Burkey
    Lilly Research Laboratories, Division of Eli Lilly and Co, Lilly Corporate Center, Indianapolis, IN 46285, USA
    Xenobiotica 32:1045-52. 2002
    ..7 h. 6. The data indicate that the disposition of LY333531 is similar in rat and dog...
  76. pmc Diels-Alder cycloadditions in water for the straightforward preparation of peptide-oligonucleotide conjugates
    Vicente Marchán
    Departament de Quimica Organica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1 11, E 08028, Barcelona, Spain
    Nucleic Acids Res 34:e24. 2006
    ..The speed of the reaction was found to vary depending on the size of the reagents, but it can be completed in 8-10 h by reacting the diene-oligonucleotide with a small excess of maleimide-peptide...
  77. ncbi Effect of ruboxistaurin on blood-retinal barrier permeability in relation to severity of leakage in diabetic macular edema
    Charlotte Strøm
    Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Denmark
    Invest Ophthalmol Vis Sci 46:3855-8. 2005
    ....
  78. pmc From a natural product lead to the identification of potent and selective benzofuran-3-yl-(indol-3-yl)maleimides as glycogen synthase kinase 3beta inhibitors that suppress proliferation and survival of pancreatic cancer cells
    Irina N Gaisina
    Department of Medicinal Chemistry and Pharmacognosy, Drug Discovery Program, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA
    J Med Chem 52:1853-63. 2009
    ..Here, we report the design, synthesis, and biological evaluation of benzofuran-3-yl-(indol-3-yl)maleimides, potent GSK-3beta inhibitors...
  79. ncbi The spermostatic and microbicidal actions of quinones and maleimides: toward a dual-purpose contraceptive agent
    Louise M Hughes
    School of Environmental and Life Sciences, Faculty of Science and IT, University of Newcastle, Callaghan, NSW, Australia
    Mol Pharmacol 76:113-24. 2009
    ..Taken together, these results have identified for the first time a novel set of cellular targets and chemical principles capable of providing simultaneous defense against both fertility and the spread of sexually transmitted disease...
  80. ncbi Evaluation of ((4-hydroxyphenyl)ethyl)maleimide for site-specific radiobromination of anti-HER2 affibody
    Eskender Mume
    Department of Chemistry, Organic Chemistry, Uppsala University, Uppsala, Sweden
    Bioconjug Chem 16:1547-55. 2005
    ..Biodistribution studies in nude mice bearing SK-OV-3 xenografts have shown tumor accumulation of 4.8 +/- 2.2% IA/g and good tumor-to-normal tissue ratios...
  81. ncbi Labeling of low-density lipoproteins using the 18F-labeled thiol-reactive reagent N-[6-(4-[18F]fluorobenzylidene)aminooxyhexyl]maleimide
    Mathias Berndt
    Institute of Radiopharmacy, Research Center Rossendorf, POB 51 01 19, D 01314 Dresden, Germany
    Nucl Med Biol 34:5-15. 2007
    ..The compound [18F]FBAM can be considered as an excellent prosthetic group for the selective and mild 18F labeling of thiol-group-containing biomolecules suitable for subsequent investigations in vitro and in vivo...
  82. ncbi Bisindolylmaleimides in anti-cancer therapy - more than PKC inhibitors
    B Pajak
    Department of Cell Ultrastructure, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
    Adv Med Sci 53:21-31. 2008
    ..Presented molecular mechanisms indicate that bisindolylmaleimides could be useful agents in anticancer therapy. They repress uncontrolled proliferation and restore the sensitivity to chemotherapy which allows eradication of cancer cells...
  83. pmc Effects of the selective bisindolylmaleimide protein kinase C inhibitor GF 109203X on P-glycoprotein-mediated multidrug resistance
    V Gekeler
    Byk Gulden GmbH, Konstanz, Germany
    Br J Cancer 74:897-905. 1996
    ....
  84. ncbi Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure
    Michael C Jaye
    GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 48:5419-22. 2005
    ....
  85. ncbi Homologous desensitization of signalling by the beta (beta) isoform of the human thromboxane A2 receptor
    Leanne P Kelley-Hickie
    School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
    Biochim Biophys Acta 1761:1114-31. 2006
    ....
  86. ncbi Design, synthesis, and biological evaluation of novel 7-azaindolyl-heteroaryl-maleimides as potent and selective glycogen synthase kinase-3beta (GSK-3beta) inhibitors
    David J O'Neill
    Drug Discovery Division, Johnson and Johnson Pharmaceutical Research and Development, L L C, Raritan, NJ 08869 0602, USA
    Bioorg Med Chem 12:3167-85. 2004
    ..Among them, compound 33 exhibited very weak inhibitions at the other 79 kinase assays, and behaved as a highly selective GSK-3beta inhibitor...
  87. ncbi The bisindolylmaleimide protein kinase C inhibitor, Ro 32-2241, reverses multidrug resistance in KB tumour cells
    J E Merritt
    Roche Discovery Welwyn, Welwyn Garden City, Herts, UK
    Cancer Chemother Pharmacol 43:371-8. 1999
    ..However, results of in vivo experiments conducted to investigate the effects of Ro 32-2241 on resistance to doxorubicin suggest that it may not be possible to achieve sufficiently high levels of Ro 32-2241 in vivo to modulate MDR...
  88. ncbi Tethered blockers as molecular 'tape measures' for a voltage-gated K+ channel
    R O Blaustein
    Department of Biochemistry, Howard Hughes Medical Institute Brandeis University, Waltham, Massachusetts 02454, USA
    Nat Struct Biol 7:309-11. 2000
    ..A portion of the S3-S4 loop is, at 17-18 ¿, considerably closer...
  89. ncbi Protein kinase Cbeta selective inhibitor LY333531 attenuates diabetic hyperalgesia through ameliorating cGMP level of dorsal root ganglion neurons
    Hyoh Kim
    Division of Neurology, Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan
    Diabetes 52:2102-9. 2003
    ..The expressions of nNOS and TTX-R Na channels were not changed with LY treatment. These results suggest that LY is effective for treating diabetic hyperalgesia through ameliorating the decrease in the nNOS-cGMP system...
  90. ncbi Cysteine 981 of the human insulin receptor is required for covalent cross-linking between beta-subunit and a thiol-reactive membrane-associated protein
    M J Garant
    Diabetes Section, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 6825, USA
    Biochemistry 39:7178-87. 2000
    ....
  91. ncbi Specific 3'-terminal modification of DNA with a novel nucleoside analogue that allows a covalent linkage of a nuclear localization signal and enhancement of DNA stability
    Yutaka Ikeda
    Department of Chemistry and Biotechnology, School of Engineering, University of Tokyo, 7 3 1 Hongo, Tokyo 113 8656, Japan
    Chembiochem 6:297-303. 2005
    ..This enhancement is mainly attributed to increased stability of the template DNA...
  92. ncbi Phosphorylation-dependent regulation of phospholipase D2 by protein kinase C delta in rat Pheochromocytoma PC12 cells
    Jung Min Han
    Department of Life Science and Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, 790 784, South Korea
    J Biol Chem 277:8290-7. 2002
    ..These results suggest that PKC delta-dependent direct phosphorylation plays an important role in the regulation of PLD2 activity in PC12 cells...
  93. ncbi Modulation of cyclin D1 and its signaling components by the phorbol ester TPA and the tyrosine phosphatase inhibitor vanadate
    S Yan
    Department of Biochemistry, Roswell Park Cancer Institute, Buffalo, New York 14260, USA
    J Cell Physiol 186:338-49. 2001
    ..These data suggest that vanadate can selectively perturb the activation of signaling components which raises the interesting issue as to how vanadate downregulates the cyclin D1 level...
  94. ncbi Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma-associated herpesvirus
    J P Zoeteweij
    Dermatology Branch, National Cancer Institute, Bethesda, MD 20892-1908, USA
    Blood 97:2374-80. 2001
    ....
  95. ncbi Phospholipase C and protein kinase C involvement in mouse embryonic stem-cell proliferation and apoptosis
    L R Quinlan
    Department of Physiology, National University of Ireland, University Road, Galway, Ireland
    Reproduction 126:121-31. 2003
    ..These results indicate that the PtdIns system is involved in the control of ES-cell proliferation and apoptosis...
  96. ncbi Cytotoxic action of phorbol esters on human pancreatic cancer cells
    Jane A Bond
    Department of Pathology, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom
    Int J Cancer 121:1445-54. 2007
    ....
  97. ncbi Stimulation of extracellular signal-regulated kinases and proliferation in rat osteoblastic cells by parathyroid hormone is protein kinase C-dependent
    J T Swarthout
    Cell and Molecular Biology Program and the Departments of Pharmacological and Physiological Science and Orthopedic Surgery, Saint Louis University School of Medicine, St. Louis, Missouri, USA
    J Biol Chem 276:7586-92. 2001
    ..Thus, activation of ERKs and proliferation by PTH is protein kinase C-dependent, but stimulation occurs independently of the EGF receptor and Ras activation...
  98. pmc Potentiation of glutamatergic synaptic transmission by protein kinase C-mediated sensitization of TRPV1 at the first sensory synapse
    Parul Sikand
    Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA
    J Physiol 581:631-47. 2007
    ..Selective targeting of TRPV1 expressed on the central terminals of sensory neurons may serve as a strategy to alleviate chronic intractable pain conditions...
  99. ncbi Hydrogen peroxide inhibits insulin signaling in vascular smooth muscle cells
    Carla D Gardner
    Department of Anatomy and Physiology, Meharry Medical College, Nashville, Tennessee 37208, USA
    Exp Biol Med (Maywood) 228:836-42. 2003
    ..We conclude that ROS inhibit a critical insulin signal transduction component required for Akt activation in VSMCs, suggesting potential cellular mechanisms of insulin resistance, which would require verification in vivo...
  100. ncbi Alpha1-adrenergic receptor stimulation induces the expression of receptor activator of nuclear factor kappaB ligand gene via protein kinase C and extracellular signal-regulated kinase pathways in MC3T3-E1 osteoblast-like cells
    Toshihiro Nishiura
    Section of Biochemistry, Department of Functional Bioscience, Fukuoka Dental College, 2 15 1 Tamura, Sawara ku, Fukuoka 814 0193, Japan
    Arch Oral Biol 52:778-85. 2007
    ..Osteoblastic cells have been demonstrated to express alpha(1)-adrenergic receptors...
  101. pmc Sustained activation of proton channels and NADPH oxidase in human eosinophils and murine granulocytes requires PKC but not cPLA2 alpha activity
    Deri Morgan
    Department of Molecular Biophysics and Physiology, Rush University Medical Center, 1750 West Harrison, Chicago, IL 60612 USA
    J Physiol 579:327-44. 2007
    ..The existing paradigm for regulation of the concerted activity of proton channels and NADPH oxidase must be revised...

Research Grants66

  1. CHEMICAL INDUCED NEPHROTOXICITY--SUCCINIMIDES
    GARY RANKIN; Fiscal Year: 2001
    ..The conjugates then either release N-aryl maleimides which can alkylate renal macromolecules (e.g...
  2. Instrument to Measure Oxygen Affinity of Hemoglobin
    Kim Vandegriff; Fiscal Year: 2004
    ..abstract_text> ..
  3. SIGNAL TRANSDUCTION AND CELL DEATH REGULATION
    Alakananda Basu; Fiscal Year: 2004
    ....
  4. Tumor Necrosis Factor-Alpha Signaling in Breast Cancer
    Alakananda Basu; Fiscal Year: 2009
    ..The long-term objective is to develop strategies to intervene with these pathways to inhibit progression of breast cancer. ..
  5. MECHANISMS OF ANESTHETIC ACTION ON SMOOTH MUSCLE
    JUDY SU; Fiscal Year: 2004
    ..Further the understanding of signal pathways of CaMKII and PKC in smooth muscle will advance understanding mechanisms of agonist-activated force maintenance in smooth muscle, as well as cell motility and migration in non-muscle cells. ..
  6. Chemistry and Pharmacology of a New Nicotine Ligands
    Alan Kozikowski; Fiscal Year: 2007
    ..Functional activity will be evaluated using established 86RbC1 efflux assays and/or whole cell patch clamp measurements. ..
  7. Microvascular Regulation During Intestinal Absorption
    HAROLD G BOHLEN; Fiscal Year: 2010
    ..A substantial fraction of the NO in blood may be from NO loading in the small arteries based on their very high wall NO concentration and represents a new form of vascular regulation. ..
  8. CHEMICAL AND PHARMACOLOGICAL STUDIES OF COCAINE ANALOGS
    Alan Kozikowski; Fiscal Year: 2004
    ....
  9. PKC Modulators for the Treatment of Alzheimer's disease
    Alan Kozikowski; Fiscal Year: 2008
    ..For the best compounds from Aim 2, perform studies in triple transgenic mice to ascertain effects on Abeta and sAPPalpha levels and plaque formation in vivo. ..
  10. BIOLOGICAL STUDIES OF PIPERIDINE ANALOGS OF COCAINE
    Alan Kozikowski; Fiscal Year: 2001
    ..4. For compounds meeting set criteria, to further evaluate their behavioral pharmacological profile in animals using intravenous drug self-administration and drug discrimination procedures. ..
  11. Diabetic Retinopathy Clinical Research Network
    Lloyd Aiello; Fiscal Year: 2005
    ..This proposal details the manner in which the specific goals of the network will be fostered under the guidance of the Study Chair. ..
  12. Effect of Drugs on Myocardial Hypoxia
    Garrett Gross; Fiscal Year: 2009
    ..Information gained from these studies will hopefully lead to new therapies to treat patients with ischemic heart disease. ..
  13. MICROVASCULAR CHARACTERISTICS OF DIABETES MELLITUS
    HAROLD BOHLEN; Fiscal Year: 2002
    ..Positive results will confirm that chronic insulin resistance predisposes the microvasculature to abnormalities of endothelial function. However, antioxidants and inhibition of beta II isoenzymes of PKC may protect endothelial function. ..
  14. DESIGN OF LIGANDS SELECTIVE FOR THE DAG SUPERFAMILY
    Alan Kozikowski; Fiscal Year: 2002
    ..To assess the effect of alterations in the ligand's hydrophobic side chain on its tumor promoting activity, studies of skin hyperplasia will be conducted. ..
  15. Chemistry and Biology of 5-HT2C Receptor Ligands for Drug Abuse
    ALAN PAUL KOZIKOWSKI; Fiscal Year: 2010
    ....
  16. PKC modulation of calcium current and anesthetic action
    GANESAN KAMATCHI; Fiscal Year: 2007
    ..abstract_text> ..
  17. Role of MRP2 and MRP4 in renal organic anion excretion
    RYAN PELIS; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  18. Epithelial Na channel (ENaC) polymorphisms in hyptertention
    James Stockand; Fiscal Year: 2007
    ..Preliminary results support the feasibility of this investigation and suggest that this line of inquiry will yield significant and novel findings. [unreadable] [unreadable]..
  19. Early Growth Response-1 (Egr-1), PKC Beta and Restenosis
    Shi Fang Yan; Fiscal Year: 2007
    ..abstract_text> ..
  20. CYTOMIMETIC ORGANIC CHEMISTRY
    FREDRIC MENGER; Fiscal Year: 2007
    ....
  21. Involvement of RUNX1 in Megakaryocytic Differentiation
    Adam Goldfarb; Fiscal Year: 2007
    ..abstract_text> ..
  22. Mechanism of Ca2+ Sensitization in Smooth Muscle
    Toshio Kitazawa; Fiscal Year: 2006
    ..abstract_text> ..
  23. CLEVELAND TRAINING PROGRAM IN CARDIOVASCULAR RESEARCH
    GEORGE DUBYAK; Fiscal Year: 2008
    ..The proposed renewal will continue to facilitate interaction among faculty and trainees and expand the culture and training excellence in cardiovascular research. ..
  24. A New Antioxidant Prevents Toxicity of HIV Proteins with Methamphetamine
    Nuran Ercal; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  25. Molecular dynamics studies of muscle proteins
    EDWARD F PATE; Fiscal Year: 2010
    ..Improved understanding of the function of myosin V and myosin VI can be anticipated to improve therapies for Griscelli syndrome and myosin Vl-based sensorineural hearing loss in humans. ..
  26. Design and Development of Pharmacotherapies for Treating Stimulant Abuse
    Frank Ivy Carroll; Fiscal Year: 2010
    ..3) To continue on a limited basis our development of selected 3-phenyltropane analogs as second-generation pharmacotherapies to treat cocaine addiction. ..
  27. Working memory deficits following brain trauma
    Pramod Dash; Fiscal Year: 2009
    ..An understanding of the mechanisms by which TBI alters dopamine signaling is critical for the development of mechanism-based intelligent pharmacological treatments for working memory deficits for brain trauma patients. ..
  28. Prefrontal cortex and memory storage
    Pramod K Dash; Fiscal Year: 2010
    ....
  29. Allenic [2 + 2 + 1] Reactions Enabling Syntheses of Natural Products with 7-Membe
    Kay M Brummond; Fiscal Year: 2010
    ..Grayanotoxin is an important molecular tool for deciphering the mechanism for gating functions of the sodium ion channels. ..
  30. Ca and Rho GTPase Control of the Neuronal Cytoskeleton
    Paul Forscher; Fiscal Year: 2009
    ..This hypothesis will be tested in the context of LPA as well as Ephrin and Slit ligands, the latter two being known to exert their chemorepellant responses via activation of Rho in the CNS. ..
  31. Egr-1, PKC Beta, Signalling and Atherosclerosis
    Shi Fang Yan; Fiscal Year: 2009
    ....
  32. Red Blood Cells, Nitric Oxide and Pulmonary Circulation
    Steven Deem; Fiscal Year: 2008
    ..abstract_text> ..
  33. COCAINE: A STUDY OF THE BIOCHEMICAL MECHANISM OF ACTION
    Frank Carroll; Fiscal Year: 2007
    ..abstract_text> ..
  34. Oxygen Carriers for Hypovolemic Circulatory Collapse
    Robert Winslow; Fiscal Year: 2007
    ..The research described in this proposal will focus on molecules and formulations specifically tailored for use in prehospital and trauma settings. ..
  35. ARK5 AMP-activated protein kinase and glucose transport
    Jonathan Fisher; Fiscal Year: 2007
    ..The proposed training will develop the candidate in his transition to an independent researcher and is critical to the candidate's long-term ability to contribute to diabetes research ..
  36. Pancreatic zymogen activation in a reconstituted system
    Edwin Thrower; Fiscal Year: 2006
    ..We plan to use this system to identify the compartment(s) responsible for zymogen processing and to examine the ATP and calcium-dependent mechanism of activation. [unreadable] [unreadable] [unreadable]..
  37. Potent inhibitors of Anthrax Lethal Factor
    Peter Vogt; Fiscal Year: 2003
    ..Libraries will be targeted using the structural information available for LF, supplemented by information from point mutations of the substrate. Information from our previous synthesis of metalloprotease inhibitors will also be used. ..
  38. C-TERMINAL INTERACTIONS OF ALPHA1-ADRENOCEPTOR SUBTYPES
    KENNETH MINNEMAN; Fiscal Year: 2003
    ..These experiments will clarify the role of C-terminal interacting proteins in a1-AR function, and the significance of C-terminal splice variants. ..
  39. DEFECTIVE ALPHA, ADRENERGIC SIGNALING IN SENESCENT RAT
    DONNA KORZICK; Fiscal Year: 2003
    ..Environment: The environment surrounding Dr. Korzick at the University of Missouri is one marked by a commitment to research and academic scholarship with major strengths in cardiovascular sciences. ..
  40. Mechanism of Thimerosal Induced Neurotoxicity
    KINSLEY KININGHAM; Fiscal Year: 2003
    ..This project will generate mechanistic data on thimerosal neurotoxicity and potentially identify specific targets for pharmacological intervention. ..
  41. G PROTEIN MEDIATED CA++ SENSITIZATION IN SMOOTH MUSCLE
    Toshio Kitazawa; Fiscal Year: 2002
    ....
  42. RENOVATION OF HUNTER RADIATION CENTER
    C Slayman; Fiscal Year: 2003
    ..These facets of the renovation will be essential to maintain the DTR at YUSM as a driving force in biomedical research at the University. ..
  43. POSTTRANSLATIONAL REGULATION OF HSF ACTIVITY
    James Bonner; Fiscal Year: 2002
    ..These will identify those cellular systems that require HSF activity in the absence of stress, and thus reveal why HSF is an essential gene in yeast. ..
  44. HYPOXIC PULMONARY VASOCANSTRICTION AND RED BLOOD CELLS
    Steven Deem; Fiscal Year: 2002
    ....
  45. STRUCTURE/FUNCTION OF ALPHA-1 ADRENERGIC RECEPTORS
    KENNETH MINNEMAN; Fiscal Year: 2002
    ..These experiments will clarify mechanisms coupling AR activation to growth and differentiation, and provide important information on differences between closely-related subtypes. ..
  46. COMBINATORIAL PHARMACOTHERAPIES FOR COCAINE DEPENDENCE
    John Cashman; Fiscal Year: 2001
    ..The study will provide an understanding of the structural and pharmaceutical properties of hDAT antagonists. The work will lead to new insight into the preparation of human medications necessary in the cessation of cocaine abuse. ..
  47. ANALYSIS OF MOTOR PROTEIN FUNCTION
    Edward Pate; Fiscal Year: 2004
    ..Although this approach will be shown to be a two-way street, the most significant advantage clearly accrues to the much less studied microtubule motor family. ..
  48. Multivalent gp41 Peptides as Novel Immunogens
    Lai Xi Wang; Fiscal Year: 2004
    ..The structure-immunogenicity relationships will be evaluated. It is expected that the proposed studies will yield important new data with significant relevance to the development of an effective HIV-1 vaccine. ..
  49. NOVEL PHARMACOTHERAPIES FOR COCAINE DEPENDENCE
    Frank Carroll; Fiscal Year: 2001
    ..An ideal candidate compound would not only have efficacy in the preclinical models but would be safe, orally active, and potent, would not show tolerance or sensitization, and if abusable, would be less so than cocaine. ..
  50. Iron and O2 in the Regulation of P. aeruginosa Virulence
    Michael Vasil; Fiscal Year: 2003
    ..This project will investigate the role of PA-Fur and PA-Fur regulated genes in the pathogenesis of P. aeruginosa infections for the ultimate goal or developing novel antimicrobial agents against this formidable opportunist. ..
  51. EGF, Oxidants & Intestinal Barrier Integrity
    Ali Banan; Fiscal Year: 2006
    ..abstract_text> ..
  52. Protective Mechanism of an Anti-Inflammatory Herbal Mix
    Ali Banan; Fiscal Year: 2006
    ..abstract_text> ..
  53. Regulation of PKC alpha in Alcoholic Myocytes
    Michele Solem; Fiscal Year: 2005
    ..The objective is to better define the sequence of events that are associated with alcohol-impaired alterations in IGF1 signaling. ..
  54. Redox control of Nrf2/ARE by thioredoxin and GSH
    Jason Hansen; Fiscal Year: 2005
    ..The roles of GSH and cytosolic and nuclear TRX during NRF2 activation and binding will provide an essential foundation for future developmental toxicology. ..
  55. Regulation of vascular smooth muscle calcium sensitivity
    Paul H Ratz; Fiscal Year: 2010
    ..The Specific Aim of this study will be to test the hypothesis that ROK and PKCzeta both mediate KCI- induced Ca sensitization of FA, and that iPLA2 and PI3K are required as upstream activators of ROK and PKCzeta. ..
  56. REGULATION OF DETRUSOR SMOOTH MUSCLE CONTRACTION
    PAUL RATZ; Fiscal Year: 2005
    ..Collectively, these studies will provide new insights into the cellular mechanisms regulating DSM contractions. ..
  57. MATRIX METALLOPROTEINASE AND APOPTOSIS IN BRAIN TRAUMA
    ENG LO; Fiscal Year: 2004
    ..To date, there are not effective treatments for traumatic brain injury. Results from these proposed experiments will help identify MMP and upstream MAP kinase pathways as viable therapeutic targets for this devastating condition. ..
  58. CD47 as a neurovascular target for stroke therapy
    Eng H Lo; Fiscal Year: 2010
    ..Proof-of-concept data collected here may lead to the development of CD47 as a novel neurovascular target for stroke therapy. ..
  59. BRAIN CELL APOPTOSIS AFTER INTRACEREBRAL HEMORRHAGE
    ENG LO; Fiscal Year: 2003
    ..Results may be used to improve the clinical management and treatment of intracerebral hemorrhage. ..
  60. Matrix metalloproteinase-9 mediated cell death in stroke
    ENG LO; Fiscal Year: 2009
    ..Our lab and others have established MMP-9 as a key extracellular protease that modifies neurovascular homeostasis. These proposed studies should help reveal the mechanisms of MMP-9 mediated cell death in stroke. ..
  61. THE ONCOGENICITY OF WINGED HELIX PROTEINS
    Peter Vogt; Fiscal Year: 2003
    ..The nature of activating mutations, the interactions with the preinitiation complex, and the identity and function of target genes will reveal novel molecular targets for therapeutic intervention. ..
  62. TARGET-GUIDED DEVELOPMENT OF SPECIFIC AKT INHIBITORS
    Peter Vogt; Fiscal Year: 2008
    ..4) Investigate the structure-activity relationship through in situ click chemistry and optimize inhibitors for potency, selectivity and cell-based activity ..
  63. Controlling the Max Network
    Peter Vogt; Fiscal Year: 2008
    ..The proposed work on stabilizers in the Myc-Max network could open the door to a new way of influencing and directing cell growth. ..
  64. tPA plus MMP inhibition for combination stroke therapy
    Eng H Lo; Fiscal Year: 2010
    ..abstract_text> ..
  65. MECHANISMS OF HEMORRHAGE AND EDEMA IN TPA STROKE THERAPY
    ENG LO; Fiscal Year: 2006
    ..This proposal should fit the goals of the Stroke PRG because it examines novel mechanisms that link tPA, cell signaling, MMPs, and hemorrhagic transformation in the neurovascular unit. ..