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| enzyme inhibitorsSummarySummary: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Top Publications
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Publications
Role of NF-kappaB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell deathAlexander Arlt
1Laboratory of Molecular Gastroenterology and Hepatology, 1st Department of Medicine, University of Kiel, Germany
Oncogene 22:3243-51. 2003....
Epigenetic programming by maternal behaviorIan C G Weaver
Douglas Hospital Research Center, 6875 LaSalle Blvd, , , Canada
Nat Neurosci 7:847-54. 2004..Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible...
EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapyJ Guillermo Paez
Departments of Medical Oncology and Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Science 304:1497-500. 2004..These results suggest that EGFR mutations may predict sensitivity to gefitinib...
Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activationK P Hoeflich
Ontario Cancer Institute Princess Margaret Hospital, Toronto, Canada
Nature 406:86-90. 2000..Thus, GSK-3beta facilitates NF-kappaB function...
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylaseS Imai
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
Nature 403:795-800. 2000..These findings provide a molecular framework of NAD-dependent histone deacetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes...
Infections with oseltamivir-resistant influenza A(H1N1) virus in the United StatesNila J Dharan
Epidemic Intelligence Service, Office of Workforce and Career Development Assigned to Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Rd, MS A 32, Atlanta, GA 30333, USA
JAMA 301:1034-41. 2009..Early surveillance data suggest that the prevalence of oseltamivir resistance among A(H1N1) viruses will most likely be higher during the 2008-2009 season...
Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)Linda Vermeulen
Department of Molecular Biology, University of Gent VIB, K L Ledeganckstraat 35, B 9000 Gent, Belgium
EMBO J 22:1313-24. 2003..This effect represents, together with phosphorylation of nucleosome components such as histone H3, an essential step leading to selective transcriptional activation of NF-kappaB-dependent gene expression...
Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formationF G Gervais
Department of Pharmacology, Biochemistry, and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Merck Research Laboratories, Kirkland, Quebec, Canada
Cell 97:395-406. 1999..Caspases thus appear to play a dual role in proteolytic processing of APP and the resulting propensity for A beta peptide formation, as well as in the ultimate apoptotic death of neurons in Alzheimer's disease...
A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cellsEdgar R Wood
Department of Computational, Analytical and Structural Sciences, GlaxoSmithKline, Inc, Research Triangle Park, North Carolina 27709, USA
Cancer Res 64:6652-9. 2004..The differences in the off-rates of these drugs and the ability of GW572016 to inhibit ErbB-2 can be explained by the enzyme-inhibitor structures...
Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitorsPurva Bali
Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida 33612, USA
J Biol Chem 280:26729-34. 2005..Depletion of HDAC6 sensitized human leukemia cells to HAA-HDIs and proteasome inhibitors...
Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosisHaim Y Cohen
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115 USA
Mol Cell 13:627-38. 2004..We demonstrate that increased acetylation of Ku70 disrupts the Ku70-Bax interaction and coincides with cytoplasmic accumulation of CBP. These results shed light on the role of acetyltransferases as tumor suppressors...
SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinaseB L Bennett
Signal Research Division, Celgene Corporation, 5555 Oberlin Drive, San Diego, CA 92121 USA
Proc Natl Acad Sci U S A 98:13681-6. 2001..Our study supports targeting JNK as an important strategy in inflammatory disease, apoptotic cell death, and cancer...
New insights on the use of desipramine as an inhibitor for acid ceramidaseSaeed Elojeimy
Department of Microbiology and Immunology, Medical University of South Carolina, P.O. Box 250504, 173 Ashley Avenue, Charleston, SC 29425, USA
FEBS Lett 580:4751-6. 2006..This study reveals a new mechanism of action for desipramine...
ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor modelsCherrie K Donawho
Abbott Laboratories, Abbott Park, Illinois 60064 6074, USA
Clin Cancer Res 13:2728-37. 2007..To evaluate the preclinical pharmacokinetics and antitumor efficacy of a novel orally bioavailable poly(ADP-ribose) polymerase (PARP) inhibitor, ABT-888...
Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cellsP A Marks
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
J Natl Cancer Inst 92:1210-6. 2000..The hydroxamic acid-based HPCs are potentially effective agents for cancer therapy and, possibly, cancer chemoprevention...
The specificities of protein kinase inhibitors: an updateJenny Bain
Division of Signal Transduction Therapy, School of Life Sciences, MSI/WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
Biochem J 371:199-204. 2003..33 microM) and p38-regulated/activated kinase (PRAK; IC(50)=1.0 microM)...
11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid responseJeremy W Tomlinson
Endocrinology, Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2TH, UK
Endocr Rev 25:831-66. 2004..Therapeutic inhibition of 11beta-HSD1 reductase activity in patients with obesity and the metabolic syndrome, as well as in glaucoma and osteoporosis, remains an exciting prospect...
Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrestR A Fratti
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
J Cell Biol 154:631-44. 2001..tuberculosis. This study also identifies mycobacterial phosphoinositides as products with specialized toxic properties, interfering with discrete trafficking stages in phagosomal maturation...
Crystal structures of anaplastic lymphoma kinase in complex with ATP competitive inhibitorsRoberto T Bossi
Nerviano Medical Sciences S r l, Viale Pasteur 10, 20014 Nerviano MI, Italy
Biochemistry 49:6813-25. 2010..Finally, mapping of the activating mutations associated with neuroblastoma onto our structures may explain the roles these residues have in the activation process...
High level soluble production of functional ribonuclease inhibitor in Escherichia coli by fusing it to soluble partnersWanhua Guo
Department of Nuclear Medicine, Nanjing University, Nanjing 210008, People s Republic of China
Protein Expr Purif 77:185-92. 2011..And a convenient two-step immobilized metal affinity chromatography (IMAC) method has been implemented in our study, comparing with the traditional RNase A affinity chromatography method...
Activity of any class IA PI3K isoform can sustain cell proliferation and survivalLazaros C Foukas
Centre for Cell Signalling, Institute of Cancer, Queen Mary University of London, London EC1M 6BQ, United Kingdom
Proc Natl Acad Sci U S A 107:11381-6. 2010..Such functional redundancy of class IA PI3K isoforms upon sustained PI3K inhibition has implications for the development and use of PI3K inhibitors in cancer...
Gilenya (FTY720) inhibits acid sphingomyelinase by a mechanism similar to tricyclic antidepressantsGlyn Dawson
Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA
Biochem Biophys Res Commun 404:321-3. 2011....
Histone deacetylase inhibitors induce remission in transgenic models of therapy-resistant acute promyelocytic leukemiaL Z He
Molecular Biology Program and Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Division, Graduate School of Medical Sciences, Cornell University, New York, New York 10021, USA
J Clin Invest 108:1321-30. 2001..In vivo, HDACIs induced accumulation of acetylated histones in target organs. Strikingly, this combination of agents induced leukemia remission and prolonged survival, without apparent toxic side effects...
Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complexX Nan
Institute of Cell and Molecular Biology, University of Edinburgh, UK
Nature 393:386-9. 1998..The data suggest that two global mechanisms of gene regulation, DNA methylation and histone deacetylation, can be linked by MeCP2...
Pharmacological inhibition of glucosylceramide synthase enhances insulin sensitivityJohannes M Aerts
Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Diabetes 56:1341-9. 2007....
Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcriptionKaranam Balasubramanyam
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India
J Biol Chem 279:51163-71. 2004..Thus, non-toxic curcumin, which targets p300/CBP, may serve as a lead compound in combinatorial HIV therapeutics...
HDAC6, at the crossroads between cytoskeleton and cell signaling by acetylation and ubiquitinationC Boyault
INSERM, U823, Equipe Epigénétique et Signalisation Cellulaire, Institut Albert Bonniot, Universite Joseph Fourier, Domaine de la Merci, Grenoble, La Tronche Cedex, France
Oncogene 26:5468-76. 2007....
STIM1, an essential and conserved component of store-operated Ca2+ channel functionJack Roos
Torrey Pines Therapeutics, Inc, La Jolla, CA 92037, USA
J Cell Biol 169:435-45. 2005..We propose that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels...
Chromatin-modifying agents permit human hematopoietic stem cells to undergo multiple cell divisions while retaining their repopulating potentialHiroto Araki
Section of Hematology Oncology, Department of Medicine, University of Illinois at Chicago, 909 S Wolcott Avenue, Chicago, IL 60612, USA
Blood 109:3570-8. 2007..These data indicate that HSC treated with chromatin-modifying agents are capable of undergoing repeated cell divisions in vitro while retaining their marrow-repopulating potential...
Discovery of adamantyl ethanone derivatives as potent 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitorsXiangdong Su
Medicinal Chemistry, Department of Pharmacy and Pharmacology and Sterix Ltd, University of Bath, Bath BA2 7AY, UK
ChemMedChem 5:1026-44. 2010..Comparison of the publicly available X-ray crystal structures of human 11beta-HSD1 led to docking studies of the potent compounds, revealing how these molecules may interact with the enzyme and cofactor...
Dichloroacetate induces apoptosis and cell-cycle arrest in colorectal cancer cellsB M Madhok
Section of Translational Anaesthesia and Surgery, University of Leeds, Level 7 Clinical Sciences Building, St James s University Hospital, Leeds, UK
Br J Cancer 102:1746-52. 2010..Our aim was to determine if switching metabolism from glycolysis towards mitochondrial respiration would reduce growth preferentially in colorectal cancer cells over normal cells, and to examine the underlying mechanisms...
Endocrine resistance associated with activated ErbB system in breast cancer cells is reversed by inhibiting MAPK or PI3K/Akt signaling pathwaysSandra E Ghayad
Universite de Lyon, France
Int J Cancer 126:545-62. 2010..In conclusion, the combination of MAPK and PI3K inhibitors represents a promising strategy to overcome endocrine therapy resistance in ER+ breast cancer patients...
Reactive oxygen species, antioxidants, and the mammalian thioredoxin systemJ Nordberg
Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
Free Radic Biol Med 31:1287-312. 2001..Dinitrohalobenzenes constitute a unique class of immunostimulatory TrxR inhibitors and we consider the immunomodulatory effects of dinitrohalobenzene compounds in view of their reactions with the Trx system...
Antizyme inhibitor: mysterious modulator of cell proliferationU Mangold
Program in Vascular Biology, Children s Hospital, Karp Family Building, 1 Blackfan Circle, Boston, Massachusetts 02115, USA
Cell Mol Life Sci 63:2095-101. 2006..AZI inactivates all members of the antizyme family, reactivates ODC and prevents the proteolytic degradation of ODC, which may suggest a role for AZI in tumor progression...
Growth inhibition of human malignant glioma cells induced by the PI3-K-specific inhibitorTakashi Shingu
Department of Biochemistry and Neurosurgery, Shimane Medical University, Izumo, Japan
J Neurosurg 98:154-61. 2003..The authors examined the effects of the PI3-K inhibitor 2-(4-morpholinyl)-8-phenylchromone (LY294002) on human malignant glioma cells, and compared these effects on PTEN-deficient cells with those on PTEN-wild-type (PTEN-wt) cells...
Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivoMatthias Selbach
, Abt. Molekulare Biologie, Schumannstrasse 20/21, D-10117 Berlin, Germany
J Biol Chem 277:6775-8. 2002....
Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidantSabine Heumüller
Institut für Kardiovaskuläre Physiologie, Johann Wolfgang Goethe Universitat, Theodor Stern Kai 7, D 60596 Frankfurt am Main, Germany
Hypertension 51:211-7. 2008..These observations indicate that apocynin predominantly acts as an antioxidant in endothelial cells and vascular smooth muscle cells and should not be used as an NADPH oxidase inhibitor in vascular systems...
Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemiasIvana Gojo
University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, USA
Blood 109:2781-90. 2007..No responses by classical criteria were seen. Our results show that MS-275 effectively inhibits HDAC in vivo in patients with advanced myeloid leukemias and should be further tested, preferably in patients with less-advanced disease...
Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in DrosophilaJ S Steffan
Department of Psychiatry and Human Behavior, Gillespie 2121, University of California, Irvine, California 92697, USA
Nature 413:739-43. 2001..These findings raise the possibility that therapy with HDAC inhibitors may slow or prevent the progressive neurodegeneration seen in Huntington's disease and other polyglutamine-repeat diseases, even after the onset of symptoms...
Targeting mitochondrial glutaminase activity inhibits oncogenic transformationJian Bin Wang
Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA
Cancer Cell 18:207-19. 2010..These findings highlight a previously unappreciated connection between Rho GTPase activation and cellular metabolism and demonstrate that targeting glutaminase activity can inhibit oncogenic transformation...
Induction of the mitochondrial permeability transition mediates the killing of HeLa cells by staurosporineM Tafani
Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
Cancer Res 61:2459-66. 2001..Phosphorylation of Bad prevents Bax translocation. Caspases participate in the events related to cell killing that occur subsequent to induction of the MPT...
Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitorsStanley F Barnett
Department of Cancer Research, Merck and Company, Sumneytown Pike, West Point, PA 19454, USA
Biochem J 385:399-408. 2005....
Natural products as alpha-amylase and alpha-glucosidase inhibitors and their hypoglycaemic potential in the treatment of diabetes: an updateR Tundis
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Nutrition and Health Sciences, University of Calabria, 87036 I Rende CS, Italy
Mini Rev Med Chem 10:315-31. 2010..This article reviews recent data on plant extracts and isolated natural compounds that are being tested for their hypglycaemic activity, highlights ongoing research and considers the future persepctives...
The 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor INCB13739 improves hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapyJulio Rosenstock
Dallas Diabetes and Endocrine Center at Medical City, Dallas, Texas, USA
Diabetes Care 33:1516-22. 2010..The efficacy and safety of the 11betaHSD1 inhibitor INCB13739 were assessed when added to ongoing metformin monotherapy in patients with type 2 diabetes exhibiting inadequate glycemic control (A1C 7-11%)...
Nutrient sensor O-GlcNAc transferase regulates breast cancer tumorigenesis through targeting of the oncogenic transcription factor FoxM1S A Caldwell
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA
Oncogene 29:2831-42. 2010..These findings identify O-GlcNAc as a novel mechanism through which alterations in glucose metabolism regulate cancer growth and invasion and suggest that OGT may represent novel therapeutic targets for breast cancer...
Antizyme and antizyme inhibitor, a regulatory tangoChaim Kahana
Department of Molecular Genetics, The Weizmann Institute of Science, 76100 Rehovot, Israel
Cell Mol Life Sci 66:2479-88. 2009....
Characterization of the fatty acid amide hydrolase inhibitor cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester (URB597): effects on anandamide and oleoylethanolamide deactivationDarren Fegley
Department of Pharmacology, University of California, Irvine CA 92697-4625, USA
J Pharmacol Exp Ther 313:352-8. 2005..The results also suggest that an enzyme distinct from FAAH catalyzes OEA hydrolysis in the duodenum, where this lipid substance acts as a local satiety factor...
Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5J A Bibb
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
Nature 410:376-80. 2001..Our results suggest that changes in Cdk5 levels mediated by DeltaFosB, and resulting alterations in signalling involving D1 dopamine receptors, contribute to adaptive changes in the brain related to cocaine addiction...
Discovery and evaluation of inhibitors of human sphingosine kinaseKevin J French
Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA
Cancer Res 63:5962-9. 2003..These compounds are the first examples of nonlipid inhibitors of SK with in vivo antitumor activity and so provide leads for additional development of inhibitors of this important molecular target...
Blockade of glucocorticoid excess at the tissue level: inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 as a therapy for type 2 diabetesChristopher Fotsch
Department of Medicinal Chemistry, Amgen Inc, Thousand Oaks, California 91320, USA
J Med Chem 51:4851-7. 2008
Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphomaQin C Ryan
Clinical Trials Unit, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA
J Clin Oncol 23:3912-22. 2005..Histone deacetylase inhibition was observed in peripheral-blood mononuclear-cells. Based on PK data from the q14-day schedule, a more frequent dosing schedule, weekly x 4, repeated every 6 weeks is presently being evaluated...
Design, synthesis, and structure-activity relationships of alkylcarbamic acid aryl esters, a new class of fatty acid amide hydrolase inhibitorsGiorgio Tarzia
Istituto di Chimica Farmaceutica e Tossicologica, , Piazza del Rinascimento 6, Italy
J Med Chem 46:2352-60. 2003..URB524 (N-cyclohexylcarbamic acid biphenyl-3-yl ester, 9g) is the most potent compound of the series (IC(50) = 63 nM) and was therefore selected for further optimization...
Long-term treatment with novel glycogen synthase kinase-3 inhibitor improves glucose homeostasis in ob/ob mice: molecular characterization in liver and muscleOksana Kaidanovich-Beilin
Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
J Pharmacol Exp Ther 316:17-24. 2006..Our studies show that long-term treatment with GSK-3 inhibitor improves glucose homeostasis in ob/ob mice and demonstrates a novel role of GSK-3 in regulating hepatic CREB activity and expression of muscle GLUT4...
Topoisomerase I inhibitors: camptothecins and beyondYves Pommier
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892 4255, USA
Nat Rev Cancer 6:789-802. 2006....
Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium valproate and lithiumPatrizia De Sarno
Department of Psychiatry and Behavioral Neurobiology, Sparks Center 1057, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA
Neuropharmacology 43:1158-64. 2002....
Manipulation of alternative splicing by a newly developed inhibitor of ClksMichiko Muraki
Laboratory of Gene Expression, School of Biomedical Science, Department of Functional Genomics, Medical Research Institute, Tokyo Medical and Dental University, Japan
J Biol Chem 279:24246-54. 2004....
Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibitionJeffrey F Ohren
Department of Discovery Technologies, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA
Nat Struct Mol Biol 11:1192-7. 2004..Thus, the structures reported here reveal a novel, noncompetitive mechanism for protein kinase inhibition...
Phosphorylation of p38 MAPK induced by oxidative stress is linked to activation of both caspase-8- and -9-mediated apoptotic pathways in dopaminergic neuronsWon Seok Choi
Department of Biology and Protein Network Research Center, Yonsei University College of Science, 134 Shinchon dong, Seodaemoon Gu, Seoul 120 749, Korea
J Biol Chem 279:20451-60. 2004....
Ras family signaling: therapeutic targetingAdrienne D Cox
University of North Carolina at Chapel Hill, North Carolina 27599, USA
Cancer Biol Ther 1:599-606. 2002..We review the current status of anti-Ras drug development, issues that have complicated their progression to the clinic, and possible future strategies for targeting Ras...
Genetic knockout and pharmacologic inhibition of neuronal nitric oxide synthase attenuate nerve injury-induced mechanical hypersensitivity in miceYun Guan
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 355 Ross, 720 Rutland Ave, Baltimore, Maryland 21205, USA
Mol Pain 3:29. 2007..Our findings suggest that nNOS, especially in the dorsal root ganglion, may participate in the development and/or maintenance of mechanical hypersensitivity after nerve injury...
Indirubins inhibit glycogen synthase kinase-3 beta and CDK5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A property common to most cyclin-dependent kinase inhibitors?S Leclerc
CNRS, Cell Cycle Group, Station Biologique, BP 74, Roscoff 29682 Cedex, Bretagne, France
J Biol Chem 276:251-60. 2001..Indirubins constitute the first family of low nanomolar inhibitors of GSK-3 beta to be described...
Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from deathD A Cross
Neurology Centre of Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, Harlow, Essex, UK
J Neurochem 77:94-102. 2001....
Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutantsPatrick J Collins
MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
Nature 453:1258-61. 2008..7) and H1N1 (ref. 8) viruses with neuraminidases carrying these mutations, our results indicate that it would be prudent for pandemic stockpiles of oseltamivir to be augmented by additional antiviral drugs, including zanamivir...
Chitinases and chitinase-like proteins: potential therapeutic targets for the treatment of T-helper type 2 allergiesT E Sutherland
Ashworth Laboratories, Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, UK
Clin Exp Allergy 39:943-55. 2009..chitinase inhibition leads to an attenuated allergic response, several strategies are being used to develop enzyme inhibitors for therapeutic use in human diseases...
Phase II open label study of valproic acid in spinal muscular atrophyKathryn J Swoboda
Departments of Neurology, Pediatrics, Neonatology and General Clinical Research Center, University of Utah School of Medicine, Salt Lake City, Utah, United States of America
PLoS ONE 4:e5268. 2009..TRIAL REGISTRATION: ClinicalTrials.gov...
Phosphoinositide signalling in cancer: beyond PI3K and PTENTom D Bunney
The Institute of Cancer Research, Section for Cell and Molecular Biology, Chester Beatty Laboratories, Fulham Road, London SW3 6JB, UK
Nat Rev Cancer 10:342-52. 2010..Studies of these enzymes are providing new insights into the mechanisms and the extent of their involvement in cancer, highlighting new potential targets for therapeutic intervention...
11beta-hydroxysteroid dehydrogenase type 1 and obesityNicholas M Morton
Endocrinology Unit, Centre for Cardiovascular Sciences, Queens Medical Research Institute, Edinburgh University, Edinburgh, UK
Front Horm Res 36:146-64. 2008....
Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemiaM J Eliasson
Department of Pharmacology and Molecular Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Nat Med 3:1089-95. 1997....
Radiation-induced cell cycle arrest compromised by p21 deficiencyJ Brugarolas
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA
Nature 377:552-7. 1995..However, p21-/- mouse embryo fibroblasts are impaired in their ability to undergo G1 arrest following DNA damage...
Development of anaplastic lymphoma kinase (ALK) small-molecule inhibitors for cancer therapyRongshi Li
High Throughput Medicinal Chemistry, ChemBridge Research Laboratories, 16981 Via Tazon, Suites K, San Diego, California 92127, USA
Med Res Rev 28:372-412. 2008....
Protective effects of the urocortin homologues stresscopin (SCP) and stresscopin-related peptide (SRP) against hypoxia/reoxygenation injury in rat neonatal cardiomyocytesA Chanalaris
Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
J Mol Cell Cardiol 35:1295-305. 2003..In addition, we showed that SCP and UCN are potent activators of the p42/44 MAPK pathway, with SRP able to induce phosphorylation of p42/44 MAPK as well, albeit not as pronounced...
Calcium/calmodulin-dependent protein kinase II binds to Raf-1 and modulates integrin-stimulated ERK activationMaddalena Illario
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita Federico II, Napoli, 80131 Italy
J Biol Chem 278:45101-8. 2003..These findings also provide evidence supporting the possible existence of cross-talk between other intracellular pathways involving CaMKII and Raf-1...
Nitric oxide-mediated promotion of mammary tumour cell migration requires sequential activation of nitric oxide synthase, guanylate cyclase and mitogen-activated protein kinaseLorraine C Jadeski
Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, Canada
Int J Cancer 106:496-504. 2003..Since NOS activity is positively associated with human breast cancer progression, the present results are relevant for development of therapeutic modalities for this disease...
LPS regulate ERK1/2-dependent signaling in cardiac fibroblasts via PKC-mediated MKP-1 inductionPhilipp Stawowy
Department of Medicine/Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany
Biochem Biophys Res Commun 303:74-80. 2003..This might be relevant with regard to the decreased MAPK activity and increased levels in MKPs reported during chronic heart failure in humans...
Olanzapine produces trophic effects in vitro and stimulates phosphorylation of Akt/PKB, ERK1/2, and the mitogen-activated protein kinase p38Xiao-Hong Lu
Department of Pharmacology, LSU Health Sciences Center, Shreveport, LA 71130, USA
Brain Res 1011:58-68. 2004..Other antipsychotic drugs stimulated phosphorylation of a subset of the kinase panel, but not all three kinases. The present findings demonstrate that olanzapine has both mitogenic and neuroprotective effects in neuronal cells...
Transforming growth factor-alpha attenuates N-methyl-D-aspartic acid toxicity in cortical cultures by preventing protein synthesis inhibition through an Erk1/2-dependent mechanismValerie Petegnief
Departament de Farmacologia i Toxicologia, Institut d Investigacions Biomediques de Barcelona, CSIC IDIBAPS, Spain
J Biol Chem 278:29552-9. 2003....
NMDA-induced phosphorylation of the microtubule-associated protein MAP-2 is mediated by activation of nitric oxide synthase and MAP kinaseM Llansola
Laboratory of Neurobiology, Instituto de Investigaciones Citologicas, , Amadeo de Saboya, 4. 46010 Valencia, Spain
Eur J Neurosci 13:1283-91. 2001..The interplay between NMDA receptors-associated signal transduction pathways and MAP-2 may be involved in the modulation of neuronal responses to extracellular signals and in the regulation of neuronal function...
Ouabain is a potent promoter of growth and activator of ERK1/2 in ouabain-resistant rat renal epithelial cellsRenata I Dmitrieva
Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA
J Biol Chem 278:28160-6. 2003..These results indicate that renal epithelial cells may be a sensitive target of the ERK1/2-activating and growth-promoting effects of ouabain even in the presence of ouabain-resistant Na+, K+-ATPase...
Regulation of insulin gene transcription by ERK1 and ERK2 in pancreatic beta cellsShih Khoo
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
J Biol Chem 278:32969-77. 2003..Phosphorylation increases their functional activity and results in a cumulative transactivation of the promoter. Thus, ERK1/2 act at multiple points to transduce a glucose signal to insulin gene transcription...
Bombesin and substance P analogues differentially regulate G-protein coupling to the bombesin receptor. Direct evidence for biased agonismA C MacKinnon
Rayne Laboratory, Centre for Inflammation Research, Respiratory Medicine Unit, University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, United Kingdom
J Biol Chem 276:28083-91. 2001..This validation of the concept of biased agonism has important implications in the development of novel pharmacological agents to dissect receptor-mediated signal transduction and of highly selective drugs to treat human disease...
Role of p38 mitogen-activated protein kinase (p38 MAPK) in cytokine-induced rat islet cell apoptosisJ Saldeen
Department of Medical Cell Biology, Uppsla University, Biomedicum, P O Box 571, S 751 23 Uppsala, Sweden
Biochem Pharmacol 61:1561-9. 2001..In conclusion, cytokine-induced p38 activation participates in beta-cell apoptosis, possibly by a nitric oxide-independent mechanism or by enhancing the sensitivity to nitric oxide...
Activation of the pro-survival phosphatidylinositol 3-kinase/AKT pathway by transforming growth factor-beta1 in mesenchymal cells is mediated by p38 MAPK-dependent induction of an autocrine growth factorJeffrey C Horowitz
Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
J Biol Chem 279:1359-67. 2004....
Temporal control of NF-kappaB activation by ERK differentially regulates interleukin-1beta-induced gene expressionBingbing Jiang
Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 279:1323-9. 2004..These results reveal a novel functional role for ERK as an important temporal regulator of NF-kappaB activation and NF-kappaB-dependent gene expression...
Chronic stimulation of D1 dopamine receptors in human SK-N-MC neuroblastoma cells induces nitric-oxide synthase activation and cytotoxicityJun Chen
Department of Pediatrics, Georgetown University, Washington, DC 20007, USA
J Biol Chem 278:28089-100. 2003..These data demonstrate a novel pathway of dopamine-mediated postsynaptic oxidative stress and cell death through direct activation of NOS enzymes by D1 dopamine receptors and its associated signaling pathways...
Insulin receptor substrate-1/SHP-2 interaction, a phenotype-dependent switching machinery of insulin-like growth factor-I signaling in vascular smooth muscle cellsKen ichiro Hayashi
Department of Neuroscience D13, Osaka University Graduate School of Medicine, Yamadaoka 2 2, Suita, Osaka 565 0871, Japan
J Biol Chem 279:40807-18. 2004....
A novel role of lactosylceramide in the regulation of lipopolysaccharide/interferon-gamma-mediated inducible nitric oxide synthase gene expression: implications for neuroinflammatory diseasesRavinder Pannu
Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425, USA
J Neurosci 24:5942-54. 2004..To our knowledge this is the first report of a role of LacCer in iNOS expression and the advantage of GSL depletion in attenuating post-SCI inflammation to improve the outcome of SCI...
Phospholipase D isozymes mediate epigallocatechin gallate-induced cyclooxygenase-2 expression in astrocyte cellsShi Yeon Kim
Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137 701, Korea
J Biol Chem 279:38125-33. 2004..Collectively, our results demonstrate for the first time that PLD isozymes mediate EGCG-induced COX-2 expression through PKC and p38 in immortalized astroglial line and normal astrocyte cells...
Erk1/2 phosphorylation and reactive oxygen species formation via nitric oxide and Akt-1/Raf-1 crosstalk in cultured rat cerebellar granule cells exposed to the organic solvent 1,2,4-trimethylcyclohexaneOddvar Myhre
Norwegian Defence Research Establishment, Division for Protection and Materiel, P O Box 25, N 2027 Kjeller, Norway
Toxicol Sci 80:296-303. 2004....
Effect of erythropoietin axotomy-induced apoptosis in rat retinal ganglion cellsJochen H Weishaupt
Department of Neurology, , , Germany
Invest Ophthalmol Vis Sci 45:1514-22. 2004....
Focal adhesion kinase in netrin-1 signalingXiu Rong Ren
Department of Pathology, University of Alabama, Birmingham, Alabama 35294, USA
Nat Neurosci 7:1204-12. 2004..Taken together, these results indicate a new signaling mechanism for DCC, in which FAK is activated upon netrin-1 stimulation and mediates netrin-1 function; they also identify a critical role for FAK in axon navigation...
Arginine and Leucine regulate p70 S6 kinase and 4E-BP1 in intestinal epithelial cellsHidetoshi Ban
Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Graduate School of Medicine and Dentistry, Okayama University, Okayama 700 8558, Japan
Int J Mol Med 13:537-43. 2004..In conclusion, l-Arginine regulates p70 S6 kinase activity and phosphorylation of 4E-BP1 through mTOR signaling pathway, which involves system y(+), cationic amino acid transporters...
Angiotensin II differentially regulates interleukin-1-beta-inducible NO synthase (iNOS) and vascular cell adhesion molecule-1 (VCAM-1) expression: role of p38 MAPKBingbing Jiang
Whitaker Cardiovascular Institute, Vascular Biology Unit, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
J Biol Chem 279:20363-8. 2004....
Antioxidants N-acetylcysteine (NAC) and 2-mercaptoethanol (2-ME) affect the survival and differentiative potential of cholinergic precursors from the embryonic septal nuclei and basal forebrain: involvement of ras signalingL Ni
Department of Biological Sciences, Rutgers University/Newark, 101 Warren St, Newark, NJ 07102, USA
Brain Res Dev Brain Res 130:207-16. 2001..Treatment of the cultures with PD98059 to inhibit MEK returned cultures to a 'low-dose' phenotype. These data suggest that redox status of basal forebrain precursors affect both their survival and differentiative potential...
Stimulation of extracellular signal-regulated kinases and proliferation in rat osteoblastic cells by parathyroid hormone is protein kinase C-dependentJ 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...
nitric oxide triggers the phosphatidylinositol 3-kinase/Akt survival pathway in insulin-producing RINm5F cells by arousing Src to activate insulin receptor substrate-1Juan R Tejedo
Laboratory of Biochemistry of the Immune System, Department of Medical Biochemistry and Molecular Biology, University of Sevilla, 41009 Sevilla, Spain
Endocrinology 145:2319-27. 2004..These data strengthen the notion that NO production at physiological levels plays a role in protection from apoptosis in pancreatic beta-cells...
A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxationMario Lorenz
Medizinische Klinik mit Schwerpunkt Kardiologie, Angiologie, Pneumologie, Charit, Campus Mitte, , Berlin D-10117, Germany
J Biol Chem 279:6190-5. 2004....
Akt down-regulation of p38 signaling provides a novel mechanism of vascular endothelial growth factor-mediated cytoprotection in endothelial cellsJ P Gratton
Department of Pharmacology and Molecular Cardiobiology Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536, USA
J Biol Chem 276:30359-65. 2001..Thus, cross-talk between the Akt and p38 MAPK pathways may regulate the level of cytoprotection versus apoptosis and is a new mechanism to explain the cytoprotective actions of Akt...
Inhibition of the c-Jun N-terminal kinase signaling pathway by the mixed lineage kinase inhibitor CEP-1347 (KT7515) preserves metabolism and growth of trophic factor-deprived neuronsCharles A Harris
Department of Molecular Biology and Pharmacology, Washington University, St. Louis, Missouri 63110, USA
J Neurosci 22:103-13. 2002....
Nitric oxide regulates cGMP-dependent cAMP-responsive element binding protein phosphorylation and Bcl-2 expression in cerebellar neurons: implication for a survival role of nitric oxideElisabetta Ciani
Department of Biology, University of Bologna, Italy
J Neurochem 82:1282-9. 2002..These results not only confirm the role of CREB in neuronal survival but also provide circumstantial evidence for a novel link among NO, CREB activation and survival...
Sodium nitroprusside-induced mitochondrial apoptotic events in insulin-secreting RINm5F cells are associated with MAP kinases activationJ C Bernabé
Laboratory of Biochemistry of the Immune System, University of Sevilla, Spain
Exp Cell Res 269:222-9. 2001..Thus, we propose that exposure to apoptotic concentrations of NO triggers ERK- and p38-dependent cytochrome c release, caspase 3 activation, and PI3K-dependent Bcl-2 phosphorylation...
Phosphorylation of extracellular signal-regulated kinase in primary afferent neurons by noxious stimuli and its involvement in peripheral sensitizationYi Dai
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Hyogo 663-8501, Japan
J Neurosci 22:7737-45. 2002..Thus, pERK in primary afferents by noxious stimulation in vivo showed distinct characteristics of expression and may be correlated with the functional activity of primary afferent neurons...
Research Grants
- An Aldosterone-Endothelin Feedback Mechanism on Sodium HomeostasisCHARLES S contact WINGO; Fiscal Year: 2010..This study will examine whether endothelin acts as a local inhibitory mechanism and feedback control system on the action of aldosterone. ..
- Nanoliter Lab-on-a-chip for Protein CrystallizationVamsee Pamula; Fiscal Year: 2007..Recent antiviral drugs against AIDS are enzyme inhibitors, and their design was based on the detailed protein-drug interactions provided by crystal structures of the ..
- Pharmacogenetics and Cardiovascular EventsBruce Psaty; Fiscal Year: 2006..products of these genes represent the sites of action for many cardiovascular drugs: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, all classes of diuretics, alpha blockers, beta-blockers, central alpha ..
- Mechanism of Arsenic-Induced DiabetesMiroslav Styblo; Fiscal Year: 2002..have shown that trivalent methylated metabolites (Mas-III and DMAs-III) are more potent cytotoxins and enzyme inhibitors than iAs-III...
- Improving Outcomes in Diabetic NephropathyRobert Toto; Fiscal Year: 2003..to ESRD despite inhibition of the renin-angiotensin-aldosterone system with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs)...
- HE3 MR Diffusion & Low Dose CT Quantitation of EmphysemaDavid Gierada; Fiscal Year: 2005..proteinases in the pathogenesis of COPD is leading to searches for newer anti-inflammatory strategies and enzyme inhibitors. Though in the early stages of development, some of these new approaches may eventually provide therapy that ..
- Phase III Trial of Minocycline in ALS:I-Clinical CenterPaul Gordon; Fiscal Year: 2006..Caspase enzyme inhibitors and anti-inflammatory agents have been shown to slow progression in the ALS model (6,7,17,18)...
- Phase III Trial of Minocycline in ALS:I-Clinical CenterPaul Gordon; Fiscal Year: 2007..Caspase enzyme inhibitors and anti-inflammatory agents have been shown to slow progression in the ALS model (6,7,17,18)...
- REGULATION OF HEME OXYGENASE IN NEONATAL ANIMALSDavid Stevenson; Fiscal Year: 2001..to address the regulation of HO transcription in culture and living animals in the presence and absence of enzyme inhibitors. This proposal contains three specific aims...
- Flavoenzymes in Pyrimidine MetabolismBruce A Palfey; Fiscal Year: 2010..The results of these studies will facilitate the design of enzyme inhibitors, which may be developed into useful drug candidates...
- Renin Angioensin Aldosterone System in Drub Abuse and HIV-associated NephropathyPravin C Singhal; Fiscal Year: 2010..Our long term research goal is to develop strategies to slow down the progression as well as find a cure of this devastating kidney disease. ..
- Angiotensin II and diabetic retinopathyALFONSO SCICLI; Fiscal Year: 2003Clinical trials suggest that Angiotensin Converting Enzyme inhibitors (ACEi) slow the progression of diabetic retinopathy...
- Angiotensin II and diabetic retinopathyALFONSO SCICLI; Fiscal Year: 2006Clinical trials suggest that Angiotensin Converting Enzyme inhibitors (ACEi) slow the progression of diabetic retinopathy...
- A Family Partnership Intervention for Heart FailureSandra Dunbar; Fiscal Year: 2009..dietary sodium (24-hour urinary sodium), medication adherence to HF drugs including angiotensin converting enzyme inhibitors and diuretics (Medication Event Monitoring System), heart failure severity (brain natriuretic peptide levels)..
- Amidoglycosylation Reactions of Glycal MetallanitrenesChristian Rojas; Fiscal Year: 2007..sugars, crucial molecular components and precursors in biological systems, including structural polymers, enzyme inhibitors, and cell-surface glycoproteins...
- Role and Relevance of Pept1 in Drug Absorption, Disposition, and DynamicsDavid E Smith; Fiscal Year: 2010..g., ?-lactam antibiotics, angiotensin-converting enzyme inhibitors, antiviral nucleoside prodrugs) and potentially toxic peptidomimetics (e.g., 5-aminolevulinic acid)...
- Clinical Impact of Bradykinin Receptor PolymorphismsJames Gainer; Fiscal Year: 2005..a B2 receptor dependent-mechanism, is an integral contributor to the efficacy of angiotensin converting enzyme inhibitors. Animal studies suggest that genetic variation altering the regulation or function of the B2 receptor has ..
- ACE Inhibition and Novel Cardiovascular Risk FactorsMarco Pahor; Fiscal Year: 2004Angiotensin converting enzyme inhibitors (ACE inhibitors) may prevent cardiovascular events in high risk persons and improve skeletal muscle function in heart failure patients by means of mechanisms that are independent of blood pressure ..
