- Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3
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...
- Inhibition of GSK3beta by postconditioning is required to prevent opening of the mitochondrial permeability transition pore during reperfusion
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...
- 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...
- 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...
- Effect of oxybutynin and imidafenacin on central muscarinic receptor occupancy and cognitive function: a monkey PET study with [(11)C](+)3-MPB
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...
- Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif
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...
- Activation of RhoA and inhibition of myosin phosphatase as important components in hypertension in vascular smooth muscle
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...
- 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...
- Glycogen synthase kinase-3 is a negative regulator of extracellular signal-regulated kinase
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...
- 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...
- Inhibition of glycogen synthase kinase 3beta prevents peroxide-induced collapse of mitochondrial membrane potential in rat ventricular myocytes
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...
- Linking metabolism and immunology: diabetic nephropathy is an inflammatory disease
Katherine R Tuttle
J Am Soc Nephrol 16:1537-8. 2005
- 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
- Aqabamycins A-G: novel nitro maleimides from a marine Vibrio species. I. Taxonomy, fermentation, isolation and biological activities
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...
- A PKC-beta inhibitor treatment reverses cardiac microvascular barrier dysfunction in diabetic rats
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...
- 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
- Nanosculpting reversed wavelength sensitivity into a photoswitchable iGluR
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...
- 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
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...
- 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...
- 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...
- Constitutive activation of GSK3 down-regulates glycogen synthase abundance and glycogen deposition in rat skeletal muscle cells
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
- 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)...
- 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
- Development of methods for the synthesis of libraries of substituted maleimides and α,β-unsaturated-γ-butyrolactams
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 ..
- 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...
- Catalysis of imido group hydrolysis in a maleimide conjugate
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...
- Inactivation of glycogen synthase kinase-3beta, a downstream target of the raf-1 pathway, is associated with growth suppression in medullary thyroid cancer cells
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...
- Pharmacologic modulation of glycogen synthase kinase-3beta promotes p53-dependent apoptosis through a direct Bax-mediated mitochondrial pathway in colorectal cancer cells
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...
- 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)...
- 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...
- 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...
- 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...
- 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...
- Quality of life and objective measures of diabetic neuropathy in a prospective placebo-controlled trial of ruboxistaurin and topiramate
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...
- Validation of reference tissue model of PET ligand [¹¹C]+3-MPB for the muscarinic cholinergic receptor in the living brain of conscious monkey
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...
- 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...
- 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...
- Muscarinic receptor occupancy and cognitive impairment: a PET study with [11C](+)3-MPB and scopolamine in conscious monkeys
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...
- Synthesis and evaluation of peptidic maleimides as transglutaminase inhibitors
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...
- 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...
- 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...
- Inhibition of glycogen synthase kinase-3 represses androgen receptor activity and prostate cancer cell growth
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...
- 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...
- Glycogen synthase kinase-3 inhibitors protect central neurons against excitotoxicity
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...
- 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
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...
- Inhibition of glycogen synthase kinase-3 in androgen-responsive prostate cancer cell lines: are GSK inhibitors therapeutically useful?
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...
- 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
- 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...
- Inhibition of protein kinase Cbeta protects against diabetes-induced impairment in arachidonic acid dilation of small coronary arteries
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...
- Structure of the catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor
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...
- 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...
- 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...
- GSK3 inhibitors show benefits in an Alzheimer's disease (AD) model of neurodegeneration but adverse effects in control animals
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...
- 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...
- 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...
- Inhibition of glycogen synthase kinase-3beta is sufficient for airway smooth muscle hypertrophy
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...
- Inhibition of GSK3 differentially modulates NF-kappaB, CREB, AP-1 and beta-catenin signaling in hepatocytes, but fails to promote TNF-alpha-induced apoptosis
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...
- Glycogen synthase kinase-3 inhibitors prevent caspase-dependent apoptosis induced by ethanol in cultured rat cortical neurons
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...
- Protein kinase C modulates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by targeting the apical events of death receptor signaling
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
- Synthesis and biological evaluation of novel 4-azaindolyl-indolyl-maleimides as glycogen synthase kinase-3beta (GSK-3beta) inhibitors
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...
- 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...
- Histamine-induced vasoconstriction involves phosphorylation of a specific inhibitor protein for myosin phosphatase by protein kinase C alpha and delta isoforms
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...
- A method for bioconjugation of carbohydrates using Diels-Alder cycloaddition
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...
- 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...
- 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...
- 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...
- 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...
- 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...
- 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
- Glucocorticoids and lithium reciprocally regulate the proliferation of adult dentate gyrus-derived neural precursor cells through GSK-3beta and beta-catenin/TCF pathway
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...
- 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
- Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4)
Department of Anesthesiology, Karolinska Institute at Soder Hospital, S 118 83 Stockholm, Sweden
J Appl Physiol 96:1843-53. 2004
- A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified Hemoglobin (Hemospan) in patients undergoing major orthopedic surgery
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...
- 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...
- 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...
- Diels-Alder cycloadditions in water for the straightforward preparation of peptide-oligonucleotide conjugates
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...
- Effect of ruboxistaurin on blood-retinal barrier permeability in relation to severity of leakage in diabetic macular edema
Department of Ophthalmology, Herlev Hospital, University of Copenhagen, Denmark
Invest Ophthalmol Vis Sci 46:3855-8. 2005
- 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...
- 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...
- Evaluation of ((4-hydroxyphenyl)ethyl)maleimide for site-specific radiobromination of anti-HER2 affibody
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...
- Labeling of low-density lipoproteins using the 18F-labeled thiol-reactive reagent N-[6-(4-[18F]fluorobenzylidene)aminooxyhexyl]maleimide
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...
- Bisindolylmaleimides in anti-cancer therapy - more than PKC inhibitors
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...
- Effects of the selective bisindolylmaleimide protein kinase C inhibitor GF 109203X on P-glycoprotein-mediated multidrug resistance
Byk Gulden GmbH, Konstanz, Germany
Br J Cancer 74:897-905. 1996
- 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
- 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
- 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...
- 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...
- 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...
- Protein kinase Cbeta selective inhibitor LY333531 attenuates diabetic hyperalgesia through ameliorating cGMP level of dorsal root ganglion neurons
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...
- 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
- 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
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...
- 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...
- Modulation of cyclin D1 and its signaling components by the phorbol ester TPA and the tyrosine phosphatase inhibitor vanadate
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...
- 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
- 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...
- 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
- 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...
- Potentiation of glutamatergic synaptic transmission by protein kinase C-mediated sensitization of TRPV1 at the first sensory synapse
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...
- 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...
- 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
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...
- Sustained activation of proton channels and NADPH oxidase in human eosinophils and murine granulocytes requires PKC but not cPLA2 alpha activity
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...