heterocyclic compounds with 4 or more rings

Summary

Summary: A class of organic compounds containing four or more ring structures, one of which is made up of more than one kind of atom, usually carbon plus another atom. The heterocycle may be either aromatic or nonaromatic.

Top Publications

  1. pmc Myosin II activity regulates vinculin recruitment to focal adhesions through FAK-mediated paxillin phosphorylation
    Ana M Pasapera
    Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 188:877-90. 2010
  2. pmc Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
    Jill C Milne
    Sirtris Pharmaceuticals Inc, 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
    Nature 450:712-6. 2007
  3. ncbi Two distinct actin networks drive the protrusion of migrating cells
    A Ponti
    Department of Cell Biology, Scripps Research Institute TSRI, La Jolla, CA 92037, USA
    Science 305:1782-6. 2004
  4. ncbi Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor
    Aaron F Straight
    Department of Cell Biology and Institute of Chemistry and Cell Biology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA
    Science 299:1743-7. 2003
  5. ncbi A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states
    Roger S McIntyre
    Department of Psychiatry and Pharmacology, University of Toronto, Toronto, ON, Canada
    Bipolar Disord 11:673-86. 2009
  6. ncbi Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation
    Jerome N Feige
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM Universite Louis Pasteur, 67404, Illkirch, France
    Cell Metab 8:347-58. 2008
  7. pmc The role of dynamic instability and wavelength in arrhythmia maintenance as revealed by panoramic imaging with blebbistatin vs. 2,3-butanedione monoxime
    Qing Lou
    Department of Biomedical Engineering, Washington University, St Louis, Missouri 63130 4899, USA
    Am J Physiol Heart Circ Physiol 302:H262-9. 2012
  8. pmc Characterization of sparstolonin B, a Chinese herb-derived compound, as a selective Toll-like receptor antagonist with potent anti-inflammatory properties
    Qiaoli Liang
    Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA
    J Biol Chem 286:26470-9. 2011
  9. ncbi Myosin IIA regulates cell motility and actomyosin-microtubule crosstalk
    Sharona Even-Ram
    Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research NIDCR, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Cell Biol 9:299-309. 2007
  10. pmc Blebbistatin effectively uncouples the excitation-contraction process in zebrafish embryonic heart
    Chuanchau J Jou
    Division of Pediatric Cardiology, University of Utah, Salt Lake City, UT 84113, USA
    Cell Physiol Biochem 25:419-24. 2010

Research Grants

  1. SYNTHESIS OF ANTICANCER AGENTS
    K C Nicolaou; Fiscal Year: 2010
  2. TOTAL SYNTHESIS OF APOPTOLIDIN
    K Nicolaou; Fiscal Year: 2004
  3. Enabling Technologies for Combinatorial Chemistry
    K Nicolaou; Fiscal Year: 2005
  4. TOTAL SYNTHESIS OF NATURAL PRODUCTS
    K Nicolaou; Fiscal Year: 2002
  5. TOTAL SYNTHESIS OF AZADIRACHTIN
    K Nicolaou; Fiscal Year: 2008
  6. SYNTHESIS OF CHLOROPEPTINS, GP120 CD4 BINDING INHIBITORS
    AMOS SMITH; Fiscal Year: 2001
  7. NMR systems : 2 Bruker Avance 500 Consoles
    AMOS SMITH; Fiscal Year: 2006
  8. SYNTHESIS OF SPONGISTATIN ANTITUMOR AGENTS
    AMOS SMITH; Fiscal Year: 2007
  9. Design and Synthesis of HIV-1 Protease Inhibitors
    AMOS SMITH; Fiscal Year: 2004
  10. Effects of antipsychotic drugs on brain and behavior
    FRANK TARAZI; Fiscal Year: 2005

Detail Information

Publications219 found, 100 shown here

  1. pmc Myosin II activity regulates vinculin recruitment to focal adhesions through FAK-mediated paxillin phosphorylation
    Ana M Pasapera
    Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 188:877-90. 2010
    ....
  2. pmc Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
    Jill C Milne
    Sirtris Pharmaceuticals Inc, 790 Memorial Drive, Cambridge, Massachusetts 02139, USA
    Nature 450:712-6. 2007
    ..Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes...
  3. ncbi Two distinct actin networks drive the protrusion of migrating cells
    A Ponti
    Department of Cell Biology, Scripps Research Institute TSRI, La Jolla, CA 92037, USA
    Science 305:1782-6. 2004
    ..Productive cell advance was a function of the second colocalized network, the lamella, where actomyosin contraction was integrated with substrate adhesion...
  4. ncbi Dissecting temporal and spatial control of cytokinesis with a myosin II Inhibitor
    Aaron F Straight
    Department of Cell Biology and Institute of Chemistry and Cell Biology, Harvard Medical School, 250 Longwood Avenue, Boston, MA 02115, USA
    Science 299:1743-7. 2003
    ..Continuous signals from microtubules are required to maintain the position of the cleavage furrow, and these signals control the localization of myosin II independently of other furrow components...
  5. ncbi A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states
    Roger S McIntyre
    Department of Psychiatry and Pharmacology, University of Toronto, Toronto, ON, Canada
    Bipolar Disord 11:673-86. 2009
    ..Asenapine is approved for bipolar disorder and schizophrenia. This was a 3-week, randomized, double-blind, placebo-controlled trial of asenapine for treating acute bipolar mania...
  6. ncbi Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation
    Jerome N Feige
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM Universite Louis Pasteur, 67404, Illkirch, France
    Cell Metab 8:347-58. 2008
    ..Combined with our previous work on resveratrol, the current study further validates SIRT1 as a target for the treatment of metabolic disorders and characterizes the mechanisms underlying the therapeutic potential of SIRT1 activation...
  7. pmc The role of dynamic instability and wavelength in arrhythmia maintenance as revealed by panoramic imaging with blebbistatin vs. 2,3-butanedione monoxime
    Qing Lou
    Department of Biomedical Engineering, Washington University, St Louis, Missouri 63130 4899, USA
    Am J Physiol Heart Circ Physiol 302:H262-9. 2012
    ..This relatively high dynamic instability leads to the self-termination of arrhythmia because of the sufficiently long wavelength under blebbistatin...
  8. pmc Characterization of sparstolonin B, a Chinese herb-derived compound, as a selective Toll-like receptor antagonist with potent anti-inflammatory properties
    Qiaoli Liang
    Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA
    J Biol Chem 286:26470-9. 2011
    ..Thus, SssB may serve as a promising lead for the development of selective TLR antagonistic agents for inflammatory diseases...
  9. ncbi Myosin IIA regulates cell motility and actomyosin-microtubule crosstalk
    Sharona Even-Ram
    Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research NIDCR, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Cell Biol 9:299-309. 2007
    ..We conclude that myosin IIA negatively regulates cell migration and suggest that it maintains a balance between the actomyosin and microtubule systems by regulating microtubule dynamics...
  10. pmc Blebbistatin effectively uncouples the excitation-contraction process in zebrafish embryonic heart
    Chuanchau J Jou
    Division of Pediatric Cardiology, University of Utah, Salt Lake City, UT 84113, USA
    Cell Physiol Biochem 25:419-24. 2010
    ..In this study, we compared the effects two uncoupling agents, 2,3-Butanedione monoxime (BDM) and blebbistatin, on contractility and AP parameters in embryonic zebrafish heart...
  11. pmc Evidence for a common mechanism of SIRT1 regulation by allosteric activators
    Basil P Hubbard
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Science 339:1216-9. 2013
    ..In primary cells reconstituted with activation-defective SIRT1, the metabolic effects of STACs were blocked. Thus, SIRT1 can be directly activated through an allosteric mechanism common to chemically diverse STACs...
  12. ncbi Asenapine for long-term treatment of bipolar disorder: a double-blind 40-week extension study
    Roger S McIntyre
    Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, ON, Canada
    J Affect Disord 126:358-65. 2010
    ..We report the results of long-term treatment with asenapine in patients with bipolar I disorder...
  13. pmc Cytoskeletal coherence requires myosin-IIA contractility
    Yunfei Cai
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    J Cell Sci 123:413-23. 2010
    ..We suggest that NMIIA creates a coherent actin network through the formation of circumferential actin bundles that mechanically link elements of the peripheral actin cytoskeleton where much of the force is generated during spreading...
  14. ncbi Mechanism of blebbistatin inhibition of myosin II
    Mihaly Kovacs
    Laboratory of Molecular Cardiology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 1762, USA
    J Biol Chem 279:35557-63. 2004
    ....
  15. pmc Myosin II contributes to cell-scale actin network treadmilling through network disassembly
    Cyrus A Wilson
    Department of Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA
    Nature 465:373-7. 2010
    ....
  16. ncbi Asenapine versus olanzapine in people with persistent negative symptoms of schizophrenia
    Robert W Buchanan
    Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
    J Clin Psychopharmacol 32:36-45. 2012
    ..In conclusion, asenapine superiority over olanzapine was not observed in the core studies. Both treatments improved persistent negative symptoms, but discontinuation rates were higher with asenapine...
  17. ncbi Molecular requirements for inhibition of cytochrome p450 activities by roquefortine
    C Aninat
    CEA-Saclay, , Service de Pharmacologie et d'Immunologie, , F-91191 Gif-sur-Yvette Cedex, France
    Chem Res Toxicol 14:1259-65. 2001
    ..These studies indicate that the =N- imidazole moiety coordinates with the heme iron, and suggest that the dehydroHis moiety and the presence of a fused tetracycle play an important part in roquefortine inhibitory power...
  18. ncbi Myosin II functions in actin-bundle turnover in neuronal growth cones
    Nelson A Medeiros
    Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA
    Nat Cell Biol 8:215-26. 2006
    ....
  19. pmc Asenapine effects in animal models of psychosis and cognitive function
    Hugh M Marston
    Schering Plough Research Institute, Newhouse, Lanarkshire, UK
    Psychopharmacology (Berl) 206:699-714. 2009
    ....
  20. pmc Properties of blebbistatin for cardiac optical mapping and other imaging applications
    Luther M Swift
    Department of Pharmacology and Physiology, The George Washington University Medical Center, 2300 Eye Street, Washington, DC 20037, USA
    Pflugers Arch 464:503-12. 2012
    ..Our findings provide important new information about the properties of this myosin II inhibitor, which will aid in the proper design and interpretation of studies that use this compound...
  21. ncbi Wentilactone B from Aspergillus wentii induces apoptosis and inhibits proliferation and migration of human hepatoma SMMC-7721 cells
    Zhenwei Zhang
    Department of Biochemistry and Molecular Biology, Second Military Medical University, PR China
    Biol Pharm Bull 35:1964-71. 2012
    ..In conclusion, Wentilactone B inhibited the growth of SMMC-7721 cells by triggering apoptosis and inhibiting metastasis...
  22. ncbi Lamellarin alpha 20-sulfate, an inhibitor of HIV-1 integrase active against HIV-1 virus in cell culture
    M V Reddy
    Organic Chemistry Division I, Natural Products Laboratory, Indian Institute of Chemical Technology, Hyderabad 500 007, India
    J Med Chem 42:1901-7. 1999
    ..In addition, these single round tests rule out action against viral assembly or budding. These findings provide a new class of compounds for potential development of clinically useful integrase inhibitors...
  23. pmc Myosin complexed with ADP and blebbistatin reversibly adopts a conformation resembling the start point of the working stroke
    Balazs Takacs
    Department of Biochemistry, Eotvos University, H 1117 Budapest, Pazmany Peter setany 1 C, Hungary
    Proc Natl Acad Sci U S A 107:6799-804. 2010
    ..The results indicate that a significant fraction of the myosin.ADP.blebbistatin complex populates a previously inaccessible conformation of myosin resembling the start of the powerstroke...
  24. ncbi Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia
    John M Kane
    Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, NY 11004, USA
    J Clin Psychopharmacol 30:106-15. 2010
    ..Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms...
  25. pmc The small chemical vacuolin-1 inhibits Ca(2+)-dependent lysosomal exocytosis but not cell resealing
    Jan Cerny
    Department of Cell Biology and The CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115, USA
    EMBO Rep 5:883-8. 2004
    ..Because cells heal normally in the presence of vacuolin-1, we suggest that lysosomes are dispensable for resealing...
  26. ncbi Cortical actin turnover during cytokinesis requires myosin II
    Minakshi Guha
    Department of Physiology, University of Massachussetts Medical School, Worcester, 01605, USA
    Curr Biol 15:732-6. 2005
    ..Our observations indicate that myosin II ATPase is not required for the assembly of equatorial cortex during cytokinesis but is essential for its subsequent turnover and remodeling...
  27. pmc Blebbistatin and blebbistatin-inactivated myosin II inhibit myosin II-independent processes in Dictyostelium
    Shi Shu
    Laboratory of Cell Biology, National Heart, Lung, and Blood Institute, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 102:1472-7. 2005
    ....
  28. ncbi Kinetic mechanism of blebbistatin inhibition of nonmuscle myosin IIb
    Bhagavathi Ramamurthy
    Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, Pennsylvania 19104 6085, USA
    Biochemistry 43:14832-9. 2004
    ..These effects are likely mediated by binding of blebbistatin within the myosin cleft that progressively closes in forming the acto-myosin rigor state...
  29. pmc Stress fibers are generated by two distinct actin assembly mechanisms in motile cells
    Pirta Hotulainen
    Institute of Biotechnology, University of Helsinki, Helsinki FI 00014, Finland
    J Cell Biol 173:383-94. 2006
    ..Based on these data, we propose a general model for assembly and maintenance of contractile actin structures in cells...
  30. pmc Sirt1 activation protects the mouse renal medulla from oxidative injury
    Wenjuan He
    Nephrology Division, Vanderbilt University Medical Center School of Medicine, Nashville, Tennessee 37232, USA
    J Clin Invest 120:1056-68. 2010
    ..We therefore suggest that Sirt1 provides a potential therapeutic target to minimize renal medullary cell damage following oxidative stress...
  31. ncbi Iloperidone, asenapine, and lurasidone: a brief overview of 3 new second-generation antipsychotics
    Leslie Citrome
    New York University School of Medicine, Department of Psychiatry, New York, NY, USA
    Postgrad Med 123:153-62. 2011
    ..Longer-term and naturalistic studies will be helpful in evaluating these agents and their role in the psychiatric armamentarium...
  32. pmc A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange
    Yi Liu
    The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd, La Jolla, California 92037, USA
    Nature 456:269-73. 2008
    ....
  33. ncbi Potent inhibition of arterial smooth muscle tonic contractions by the selective myosin II inhibitor, blebbistatin
    Thomas J Eddinger
    Department of Biological Sciences, Marquette University, Milwaukee, Wisconsin, USA
    J Pharmacol Exp Ther 320:865-70. 2007
    ....
  34. ncbi Specificity of blebbistatin, an inhibitor of myosin II
    John Limouze
    Laboratory of Molecular Cardiology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Muscle Res Cell Motil 25:337-41. 2004
    ..The drug potently inhibits Dictyostelium myosin II, but poorly inhibits Acanthamoeba myosin II. Blebbistatin did not inhibit representative myosin superfamily members from classes I, V, and X...
  35. ncbi Enhancement of myosin II/actin turnover at the contractile ring induces slower furrowing in dividing HeLa cells
    Tomo Kondo
    Department of Biological Science, Graduate School of Science, Hiroshima University, Higashi Hiroshima, 739 8526, Japan
    Biochem J 435:569-76. 2011
    ..In conclusion, we show that the enhancement of myosin II and actin turnover at the CR induced slower furrowing in dividing HeLa cells...
  36. ncbi Securinine induces p73-dependent apoptosis preferentially in p53-deficient colon cancer cells
    Sonia Rana
    Invenio Therapeutics, Cleveland, Ohio, USA
    FASEB J 24:2126-34. 2010
    ..These studies reveal a novel approach to specifically target colon cancer cells lacking p53 as well as identify a novel clinically relevant pathway to selectively induce p73 in p53-null cells...
  37. ncbi Effect of huprine X on β-amyloid, synaptophysin and α7 neuronal nicotinic acetylcholine receptors in the brain of 3xTg-AD and APPswe transgenic mice
    Monika M Hedberg
    Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Alzheimer Neurobiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden
    Neurodegener Dis 7:379-88. 2010
    ..In this study, the aim was to investigate whether HX could affect the AD-related neuropathology in vivo in two mouse models...
  38. ncbi Blebbistatin specifically inhibits actin-myosin interaction in mouse cardiac muscle
    Ying Dou
    Dept of Physiology and Pharmacology, Karolinska Institutet, SE 171 77 Stockholm, Sweden
    Am J Physiol Cell Physiol 293:C1148-53. 2007
    ..In conclusion, we show that blebbistatin is an inhibitor of the actin-myosin interaction in the organized contractile system of cardiac muscle and that its action is not due to effects on the Ca(2+) influx and activation systems...
  39. ncbi Roquefortine/oxaline biosynthesis pathway metabolites in Penicillium ser. Corymbifera: in planta production and implications for competitive fitness
    D P Overy
    Center for Microbial Biotechnology, Technical University of Denmark, BioCentrum DTU, Building 221, DK 2800 Kgs Lyngby, Denmark
    J Chem Ecol 31:2373-90. 2005
    ....
  40. pmc The small chemical vacuolin-1 alters the morphology of lysosomes without inhibiting Ca2+-regulated exocytosis
    Chau Huynh
    Section of Microbial Pathogenesis and Department of Cell Biology, Yale University School of Medicine, 295 Congress Avenue, New Haven, Connecticut 06536, USA
    EMBO Rep 6:843-7. 2005
    ..Thus, lysosomes cannot be excluded as agents of membrane repair in vacuolin-1-treated cells...
  41. ncbi Different molecular motors mediate platelet-derived growth factor and lysophosphatidic acid-stimulated floating collagen matrix contraction
    Masatoshi Abe
    Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9039, USA
    J Biol Chem 278:47707-12. 2003
    ..LPA-dependent, Rho kinase-independent force generation also was detected during fibroblast spreading on collagen-coated coverslips...
  42. pmc Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell-cell contacts
    Annette M Shewan
    Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Australia
    Mol Biol Cell 16:4531-42. 2005
    ..We propose that Myosin 2 is a key effector of Rho-Rho kinase signaling that regulates cell-cell adhesion by determining the ability of cells to concentrate cadherins at contacts in response to homophilic ligation...
  43. ncbi Molecular determinants of topoisomerase I poisoning by lamellarins: comparison with camptothecin and structure-activity relationships
    Esther Marco
    Departamento de Farmacologia, Universidad de Alcala, E 28871 Madrid, Spain
    J Med Chem 48:3796-807. 2005
    ..The deleterious effect of replacing the 20-OH in LMD with a hydrogen was confirmed using a set of thermodynamic integration free energy simulations...
  44. ncbi Blebbistatin, a myosin II inhibitor, is photoinactivated by blue light
    Takeshi Sakamoto
    Laboratory of Molecular Cardiology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1762, USA
    Biochemistry 44:584-8. 2005
    ..This property may be useful in locally reversing the action of blebbistatin treatment in a cell. However, caution should be exercised as free radicals may be produced upon irradiation of blebbistatin that could result in cell damage...
  45. ncbi Self-assembled micellar formulation of chafuroside A with improved anti-inflammatory effects in experimental asthma/COPD-model rats
    Satomi Onoue
    Department of Pharmacokinetics and Pharmacodynamics, and Global Center of Excellence COE Program, School of Pharmaceutical Sciences, University of Shizuoka, 52 1, Yada, Suruga ku, Shizuoka 422 8526, Japan
    Eur J Pharm Sci 45:184-9. 2012
    ..From these observations, the SAM formulation might be an efficacious approach for enhancing the therapeutic potential of CFA for treatment of inflammatory diseases...
  46. ncbi Asenapine improves phencyclidine-induced object recognition deficits in the rat: evidence for engagement of a dopamine D1 receptor mechanism
    Shikha Snigdha
    Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92697 4540, USA
    Psychopharmacology (Berl) 214:843-53. 2011
    ....
  47. pmc Differential roles for actin polymerization and a myosin II motor in assembly of the epithelial apical junctional complex
    Andrei I Ivanov
    Epithelial Pathobiology Research Unit, Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA
    Mol Biol Cell 16:2636-50. 2005
    ....
  48. ncbi Overcoming chemoresistance of non-small cell lung carcinoma through restoration of an AIF-dependent apoptotic pathway
    M A Gallego
    INSERM U 837, Universite Lille 2, Faculte de Medecine, Jean Pierre Aubert Research Centre, Place de Verdun, Lille, France
    Oncogene 27:1981-92. 2008
    ..Altogether, these data suggest that mitochondrial ROS generation is crucial for overriding the chemoresistance of NSCLC cells. Moreover, this study delineates the unique mechanism of action of lamellarins as potential anticancer agents...
  49. pmc Wentilactone B induces G2/M phase arrest and apoptosis via the Ras/Raf/MAPK signaling pathway in human hepatoma SMMC-7721 cells
    Z Zhang
    Department of Biochemistry and Molecular Biology, Faculty of Basic Medicine, Second Military Medical University, Shanghai, China
    Cell Death Dis 4:e657. 2013
    ....
  50. pmc The C-terminal tail region of nonmuscle myosin II directs isoform-specific distribution in migrating cells
    Joshua C Sandquist
    Department of Pharmacology and Cancer Biology, Duke University Medical Center Durham, NC 27710, USA
    Mol Biol Cell 19:5156-67. 2008
    ....
  51. ncbi Regulation of polarity in cells devoid of actin bundle system after treatment with inhibitors of myosin II activity
    Maria S Shutova
    Institute of Carcinogenesis, Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia
    Cell Motil Cytoskeleton 65:734-46. 2008
    ..These mechanisms could switch dependent on circumstances as fibroblasts may acquire non-contractile phenotype, not only after direct inhibition of myosin II but also in certain conditions of microenvironment...
  52. ncbi A water soluble prodrug of a novel camptothecin analog is efficacious against breast cancer resistance protein-expressing tumor xenografts
    Mika Endo
    Kamakura Research Laboratories, Pharmaceutical Research Department, Chugai Pharmaceutical Co Ltd, Kajiwara, Kanagawa, Japan
    Cancer Chemother Pharmacol 65:363-71. 2010
    ..Identification of a novel topoisomerase I inhibitor which shows superior efficacy and less individual variation than irinotecan hydrochloride (CPT-11)...
  53. ncbi Actomyosin tension is required for correct recruitment of adherens junction components and zonula occludens formation
    Yuka Miyake
    RIKEN Center for Developmental Biology, 2 2 3 Minatojima minamimachi, Chuo Ku, Kobe 650 0047, Japan
    Exp Cell Res 312:1637-50. 2006
    ..These findings suggest that tension generated by actomyosin is essential for correct AJ assembly...
  54. ncbi Optical mapping study of blebbistatin-induced chaotic electrical activities in isolated rat atrium preparations
    Natnicha Kanlop
    Department of Physiology, University of the Ryukyus School of Medicine, 207 Uehara, Nishihara, Okinawa, 903 0215, Japan
    J Physiol Sci 60:109-17. 2010
    ..We suggest that these phenomena are due to the disturbed intracellular calcium dynamics induced by the application of blebbistatin...
  55. pmc Cytoplasmic force gradient in migrating adhesive cells
    Takahiro Iwasaki
    Biophys J 94:L35-7. 2008
    ..This gradient may be responsible for the forward transport of cellular components and for maintaining the directionality during cell migration...
  56. ncbi Blebbistatin, a myosin II inhibitor, suppresses contraction and disrupts contractile filaments organization of skinned taenia cecum from guinea pig
    Masaru Watanabe
    Dept of Physiology, Tokyo Medical Univ, Japan
    Am J Physiol Cell Physiol 298:C1118-26. 2010
    ..These results suggested that blebbistatin suppressed skinned smooth muscle contraction through disruption of structure of SMM by the agent...
  57. ncbi Simultaneous inhibition of PDK1/AKT and Fms-like tyrosine kinase 3 signaling by a small-molecule KP372-1 induces mitochondrial dysfunction and apoptosis in acute myelogenous leukemia
    Zhihong Zeng
    Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M D Anderson Cancer Center, 1400 Holcombe Boulevard, Houston, TX 77030, USA
    Cancer Res 66:3737-46. 2006
    ..Taken together, our results show that the simultaneous inhibition of critical prosurvival kinases by KP372-1 leads to mitochondrial dysfunction and apoptosis of AML but not normal hematopoietic progenitor cells...
  58. pmc Non-muscle myosin II regulates survival threshold of pluripotent stem cells
    Andrea Walker
    Department of Biochemistry, University of California, Riverside, Riverside, California 29521, USA
    Nat Commun 1:71. 2010
    ..These results underscore the importance of the molecular motor, NMII, as a novel target for chemically engineering the survival and self-renewal of hPS cells...
  59. pmc Cell cycle progression after cleavage failure: mammalian somatic cells do not possess a "tetraploidy checkpoint"
    Yumi Uetake
    Department of Cell Biology, University of Massachusetts Medical School, Biotech 4, 3rd Floor, 377 Plantation St, Worcester, MA 01605, USA
    J Cell Biol 165:609-15. 2004
    ..These observations provide a functional demonstration that the tetraploidy checkpoint does not exist in normal mammalian somatic cells...
  60. ncbi Blebbistatin: use as inhibitor of muscle contraction
    Gerrie P Farman
    Center for Cardiovascular Research, Department of Physiology and Biophysics M C 901, University of Illinois at Chicago, College of Medicine Chicago, Chicago, IL 60612 7342, USA
    Pflugers Arch 455:995-1005. 2008
    ....
  61. ncbi A cytoskeletal demolition worker: myosin II acts as an actin depolymerization agent
    Lior Haviv
    Department of Chemical Engineering, Ben Gurion University of the Negev, P O Box 653, Beer Sheva 84105, Israel
    J Mol Biol 375:325-30. 2008
    ..We believe that myosin II motors may function similarly in vivo (e.g., in the disassembly of the contractile ring by fine tuning the local concentration/activity of myosin II motors)...
  62. ncbi Cancer cell mitochondria are direct proapoptotic targets for the marine antitumor drug lamellarin D
    Jerome Kluza
    Institut National de la Santé et de la Reserche Médicale U 524, Institut de Recherche sur le Cancer de Lille, France
    Cancer Res 66:3177-87. 2006
    ..Altogether, this work reinforces the pharmacologic interest of the lamellarins and defines lamellarin D as a lead in the search for treatments against chemoresistant cancer cells...
  63. pmc The role of myosin II motor activity in distributing myosin asymmetrically and coupling protrusive activity to cell translocation
    John Kolega
    Department of Pathology and Anatomical Sciences, Division of Anatomy and Cell Biology, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY 14214, USA
    Mol Biol Cell 17:4435-45. 2006
    ..Myosin II may ordinarily move anteriorly on actin filaments and pull crossed filaments into antiparallel bundles, with the resulting realignment pulling the cell body forward...
  64. ncbi Lamellarin D: a novel pro-apoptotic agent from marine origin insensitive to P-glycoprotein-mediated drug efflux
    Marie Vanhuyse
    Centre Oscar Lambret and INSERM U 524, IRCL, Institute for Cancer Research, Place de Verdun, Lille cedex F 59045, France
    Cancer Lett 221:165-75. 2005
    ..This in vitro work identifies LAM-D as a potent pro-apoptotic agent and its cytotoxic action is fully maintained in multidrug-resistant cells compared to the sensitive parental cell line...
  65. pmc Nonmuscle myosin II is responsible for maintaining endothelial cell basal tone and stress fiber integrity
    Zoe M Goeckeler
    Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, West Virginia 26506, USA
    Am J Physiol Cell Physiol 295:C994-1006. 2008
    ..Thus the inhibitory effects of blebbistatin on basal tone and induced tension are consistent with a requirement for myosin II activity to maintain stress fiber integrity...
  66. ncbi Behavioural effects and regulation of PKCalpha and MAPK by huprine X in middle aged mice
    M Ratia
    Departament de Farmacologia, de Terapeutica i de Toxicologia, Institut de Neurociencies, Universitat Autonoma de Barcelona, Spain
    Pharmacol Biochem Behav 95:485-93. 2010
    ..Results obtained herein using a sample of aged animals strongly suggest that huprine X constitutes a promising therapeutic agent for the treatment of cholinergic dysfunction underlying aging and/or dementias...
  67. ncbi The structural basis of blebbistatin inhibition and specificity for myosin II
    John S Allingham
    Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, Wisconsin 53706, USA
    Nat Struct Mol Biol 12:378-9. 2005
    ..This reveals the structural basis for its specificity and provides insight into the development of new agents...
  68. ncbi Vacuolin-1-modulated exocytosis and cell resealing in mast cells
    Gouse M Shaik
    Laboratory of Signal Transduction, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Cell Signal 21:1337-45. 2009
    ..Furthermore, our results support the concept that lysosomal exocytosis is involved in the repair of injured plasma membranes...
  69. pmc Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo
    Jesse J Smith
    Sirtris, a GSK Company, 200 Technology Square, Cambridge, MA 02139, USA
    BMC Syst Biol 3:31. 2009
    ....
  70. ncbi Phototoxicity and photoinactivation of blebbistatin in UV and visible light
    J Kolega
    Department of Pathology and Anatomical Sciences, State University of New York at Buffalo School of Medicine and Biomedical Sciences, 3435 Main Street, Buffalo, NY 14214, USA
    Biochem Biophys Res Commun 320:1020-5. 2004
    ..Blebbistatin should be used only with careful consideration of these photochemical effects...
  71. ncbi In vitro and in vivo relaxation of corpus cavernosum smooth muscle by the selective myosin II inhibitor, blebbistatin
    Xin Hua Zhang
    Department of Urology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA
    J Sex Med 6:2661-71. 2009
    ..5-5 microM) with poor inhibition of turkey gizzard smooth muscle (SM) myosin II (IC(50) approximately 80 microM). However, recently it was found that BLEB can potently inhibit mammalian arterial SM (IC(50) approximately 5 microM)...
  72. ncbi Nonmuscle myosin, force maintenance, and the tonic contractile phenotype in smooth muscle
    Albert Y Rhee
    Department of Physiology, University of Maryland, Baltimore, MD, USA
    Pflugers Arch 452:766-74. 2006
    ..These results suggest that NM myosin contributes to the mechanism of force maintenance in smooth muscle, and could suggest that the expression of NMIIB is a factor for determining the tonic contractile phenotype...
  73. ncbi Asenapine versus olanzapine in acute mania: a double-blind extension study
    Roger S McIntyre
    Department of Psychiatry and Pharmacology, University of Toronto, Toronto, ON, Canada
    Bipolar Disord 11:815-26. 2009
    ..To assess the efficacy and tolerability of asenapine versus olanzapine in the extended treatment of bipolar mania...
  74. ncbi Securinine, a GABAA receptor antagonist, enhances macrophage clearance of phase II C. burnetii: comparison with TLR agonists
    Kirk Lubick
    Veterinary Molecular Biology, Montana State University, Bozeman, MT 59718, USA
    J Leukoc Biol 82:1062-9. 2007
    ..Securinine has minimal toxicity in vivo, suggesting it or structurally similar compounds may represent novel, therapeutic adjuvants, which increase resistance to intracellular pathogens...
  75. ncbi A critical role for myosin IIb in dendritic spine morphology and synaptic function
    Jubin Ryu
    The Picower Institute for Learning and Memory, RIKEN MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Neuron 49:175-82. 2006
    ..Thus, the structure and function of spines is regulated by an actin-based motor in addition to the polymerization state of actin...
  76. ncbi Myosin regulation in the migration of tumor cells and leukocytes within a three-dimensional collagen matrix
    P Bastian
    Institute of Immunology, Witten Herdecke University, Stockumer Strasse 10, 58448 Witten, Germany
    Cell Mol Life Sci 62:65-76. 2005
    ....
  77. ncbi Efficacy and tolerability of asenapine in acute schizophrenia: a placebo- and risperidone-controlled trial
    Steven G Potkin
    Department of Psychiatry and Human Behavior, University of California, Irvine, Brain Imaging Center, CA 92697 3960, USA
    J Clin Psychiatry 68:1492-500. 2007
    ..This 6-week trial assessed the efficacy, tolerability, and safety of the investigational psychopharmacologic agent asenapine versus placebo and risperidone in patients with acute schizophrenia (DSM-IV criteria)...
  78. ncbi In vitro and in vivo relaxation of urinary bladder smooth muscle by the selective myosin II inhibitor, blebbistatin
    Xinhua Zhang
    Department of Urology, Albert Einstein College of Medicine, Bronx, NY, USA
    BJU Int 107:310-7. 2011
    ....
  79. ncbi Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia
    Olivia Frånberg
    Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz vag 2, 171 77, Stockholm, Sweden
    Psychopharmacology (Berl) 196:417-29. 2008
    ..Asenapine is a novel psychopharmacologic agent being developed for the treatment of schizophrenia and bipolar disorder...
  80. ncbi Asenapine increases dopamine, norepinephrine, and acetylcholine efflux in the rat medial prefrontal cortex and hippocampus
    Mei Huang
    Department of Psychiatry, Division of Psychopharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA
    Neuropsychopharmacology 33:2934-45. 2008
    ....
  81. ncbi Differential regional and dose-related effects of asenapine on dopamine receptor subtypes
    Frank I Tarazi
    Mailman Research Center, McLean Hospital, Harvard Medical School, Belmont, MA, USA
    Psychopharmacology (Berl) 198:103-11. 2008
    ..The novel psychopharmacologic agent, asenapine, has high affinity for a range of receptors including the dopaminergic receptors...
  82. ncbi Asenapine restores cognitive flexibility in rats with medial prefrontal cortex lesions
    David S Tait
    School of Psychology, University of St Andrews, St Andrews, Scotland, KY169RH, UK
    Psychopharmacology (Berl) 202:295-306. 2009
    ..This study examined the effect of asenapine, a novel psychopharmacologic agent being developed for schizophrenia and bipolar disorder, on cognitive dysfunction in the rat...
  83. ncbi Total synthesis and evaluation of lamellarin alpha 20-Sulfate analogues
    Christian P Ridley
    Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093 0212, USA
    Bioorg Med Chem 10:3285-90. 2002
    ..Lamellarin alpha 13,20-disulfate is a moderate inhibitor of both HIV-1 integrase and cancer cell lines. Lamellarin H is a more potent inhibitor of HIV-1 integrase but lacked the specificity required to be medicinally useful...
  84. ncbi 4,5-Diaryl-1H-pyrrole-2-carboxylates as combretastatin A-4/lamellarin T hybrids: synthesis and evaluation as anti-mitotic and cytotoxic agents
    Martin G Banwell
    Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT
    Bioorg Med Chem 14:4627-38. 2006
    ..Compounds 3-8 have all been evaluated for their anti-mitotic and cytotoxic properties and two of them, 3 and 5, display useful activities although they are less potent than combretastatin A-4...
  85. ncbi Topoisomerase I-mediated DNA cleavage as a guide to the development of antitumor agents derived from the marine alkaloid lamellarin D: triester derivatives incorporating amino acid residues
    Christelle Tardy
    INSERM UR 524 and Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, IRCL, Place de Verdun, 59045 Lille, France
    Bioorg Med Chem 12:1697-712. 2004
    ..LAM-D is the lead compound of a new promising family of antitumor agents targeting topoisomerase I and the amino acid derivatives appear to be excellent candidates for a preclinical development...
  86. pmc Comparative maps of motion and assembly of filamentous actin and myosin II in migrating cells
    Sebastien Schaub
    Laboratory of Cell Biophysics, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, Switzerland
    Mol Biol Cell 18:3723-32. 2007
    ....
  87. ncbi Synthesis and structure-activity relationship study of lamellarin derivatives
    Fumito Ishibashi
    Division of Marine Life Science and Biochemistry, Faculty of Fisheries, and Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1 14 Bunkyo machi, Nagasaki 852 8521, Japan
    J Nat Prod 65:500-4. 2002
    ....
  88. ncbi Asenapine: a novel psychopharmacologic agent with a unique human receptor signature
    M Shahid
    Schering Plough, Newhouse, Lanarkshire, UK
    J Psychopharmacol 23:65-73. 2009
    ..Our results indicate that asenapine has a unique human receptor signature, with binding affinity and antagonistic properties that differ appreciably from those of antipsychotic drugs...
  89. ncbi Lamellarin D: a novel potent inhibitor of topoisomerase I
    Michael Facompre
    Institut National de la Santé et de la Recherche Médicale U 524 and Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, Place de Verdun, 59045 Lille, France
    Cancer Res 63:7392-9. 2003
    ..Collectively, the results identify LAM-D as a novel lead candidate for the development of topoisomerase I-targeted antitumor agents...
  90. ncbi Yuzurimine-type alkaloids from Daphniphyllum yunnanense
    Ying Tong Di
    State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, People s Republic of China
    J Nat Prod 69:1745-8. 2006
    ..The structures of the new alkaloids were elucidated by spectroscopic methods. Yunnandaphnine E (6) is a novel heptacyclic yuzurimine-type alkaloid with an oxazine ring...
  91. ncbi Design and synthesis of 4-substituted indolo[3,2-e][1,2,3]triazolo[1,5-a]pyrimidine derivatives with antitumor activity
    Antonino Lauria
    Dipartimento Farmacochimico, Tossicologico e Biologico Università di Palermo, Via Archirafi 32, Palermo, Italy
    J Med Chem 51:2037-46. 2008
    ..A mechanism of action closely related to the DNA-interacting drugs can be supposed, although, alternative mechanisms, similar to those of the anthracyclines, can also operate...
  92. ncbi Approaches to the quaternary stereocentre and to the heterocyclic core in diazonamide A using the Heck reaction and related coupling reactions
    James E M Booker
    School of Chemistry, The University of Nottingham, Nottingham, NG7 2RD, UK
    Org Biomol Chem 4:4193-205. 2006
    ..X-Ray crystal structure analysis established that the quaternary centre in 64 had the same configuration as that present in diazonamide A (1)...
  93. ncbi Calyciphylline D, a novel alkaloid with an unprecedented fused-pentacyclic skeleton from Daphniphyllum calycinum
    Shizuka Saito
    Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
    Org Lett 9:1207-9. 2007
    ..2.1.0.4,8]nonane ring system, has been isolated from the leaves of Daphniphyllum calycinum (Daphniphyllaceae), and the structure and relative stereochemistry were elucidated on the basis of spectroscopic data...
  94. ncbi Daphmanidins E and F, alkaloids from Daphniphyllum teijsmannii
    Hiroshi Morita
    Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan
    J Nat Prod 69:418-20. 2006
    ..Daphmanidins E and F showed a moderate vasorelaxant effect on rat aorta...
  95. ncbi Oxidative rearrangement of indoles: a new approach to the EFHG-tetracyclic core of diazonamide A
    Cyril Poriel
    Department of Chemistry, University of Exeter, Stocker Road, Exeter EX4 4QD, United Kingdom
    J Org Chem 72:2978-87. 2007
    ..The methodology was applied to the tyrosine-indole derivative 17 to give the EFHG-tetracyclic core of diazonamide A...
  96. ncbi Approach to the homoerythrina alkaloids using a tandem N-alkylation/azomethine ylide cycloaddition
    William H Pearson
    Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109 1055, USA
    J Org Chem 72:4135-48. 2007
    ..Subsequent attempts to install the C-3 methoxy group of 1-3 are also described...
  97. ncbi Fawcettimine-related alkaloids from Lycopodium serratum
    Kazuaki Katakawa
    Graduate School of Pharmaceutical Sciences, Chiba University, 1 33 Yayoi cho, Inage Ku, Chiba 263 8522, Japan
    J Nat Prod 70:1024-8. 2007
    ..The structures of the alkaloids were elucidated on the basis of spectroscopic analysis. Some alkaloids isolated in this and previous studies (1, 2, 5, and 10) were assayed for acetylcholine esterase (AChE) inhibitory activity...
  98. ncbi Toward the synthesis of norzoanthamine: complete fragment assembly
    Martin Juhl
    Department of Chemistry, Technical University of Denmark, Building 201, Kemitorvet, DK 2800 Kgs Lyngby, Denmark
    J Org Chem 72:4644-54. 2007
    ..The final fragment coupling between lithiated fragment A (C1-C5) and aldehyde 40 (C6-C24) has also been successfully accomplished affording the entire carbon framework of the natural product...
  99. ncbi Synthesis of diazatricyclic core of Madangamines from cis-perhydroisoquinolines
    Josefina Quirante
    Laboratori de Química Orgànica, Facultat de Farmacia, Institut de Biomedicina, Universitat de Barcelona, Av Joan XXIII s n, 08028 Barcelona, Spain
    J Org Chem 73:768-71. 2008
    ..A diastereoselective allylation and reduction of amide, nitrile, and ketone groups leads to a bicyclic alcohol, which undergoes aminocyclization through the nosyl derivative to the diazatricyclic ring...
  100. ncbi Alkaloids from the twigs of Daphniphyllum calycinum
    Chuan Rui Zhang
    State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi Tech Park, Shanghai, 201203, People s Republic of China
    J Nat Prod 71:1663-8. 2008
    ..Twelve new alkaloids, caldaphnidines G-R (1-12), along with 24 known ones, were isolated from the twigs of Daphniphyllum calycinum. Their structures were elucidated by spectroscopic methods, especially two-dimensional NMR techniques...
  101. ncbi Recent advances in lamellarin alkaloids: isolation, synthesis and activity
    D Pla
    Institute for Research in Biomedicine, Barcelona Science Park, University of Barcelona, E 08028, Barcelona, Spain
    Anticancer Agents Med Chem 8:746-60. 2008
    ....

Research Grants62

  1. SYNTHESIS OF ANTICANCER AGENTS
    K C Nicolaou; Fiscal Year: 2010
    ..abstract_text> ..
  2. TOTAL SYNTHESIS OF APOPTOLIDIN
    K Nicolaou; Fiscal Year: 2004
    ..The proposed work is expected to have significant impact in the area of cancer chemotherapy and should provide enabling technologies and tools for biology and medicine. ..
  3. Enabling Technologies for Combinatorial Chemistry
    K Nicolaou; Fiscal Year: 2005
    ..abstract_text> ..
  4. TOTAL SYNTHESIS OF NATURAL PRODUCTS
    K Nicolaou; Fiscal Year: 2002
    ..3] sigmatropic rearrangement and a radical based ring closure to form the bicyclic skeleton. ..
  5. TOTAL SYNTHESIS OF AZADIRACHTIN
    K Nicolaou; Fiscal Year: 2008
    ..The proposed work is expected to impact the general areas of pharmaceutical and agricultural research, and infectious diseases in particular, through discoveries in synthetic organic chemistry and chemical biology. ..
  6. SYNTHESIS OF CHLOROPEPTINS, GP120 CD4 BINDING INHIBITORS
    AMOS SMITH; Fiscal Year: 2001
    ..abstract_text> ..
  7. NMR systems : 2 Bruker Avance 500 Consoles
    AMOS SMITH; Fiscal Year: 2006
    ..The areas of public health research include, among others, cancer, infectious diseases, neurodegenerative diseases such as Alzheimer's disease, and heart and cardiovascular disease. [unreadable] [unreadable] [unreadable]..
  8. SYNTHESIS OF SPONGISTATIN ANTITUMOR AGENTS
    AMOS SMITH; Fiscal Year: 2007
    ..abstract_text> ..
  9. Design and Synthesis of HIV-1 Protease Inhibitors
    AMOS SMITH; Fiscal Year: 2004
    ....
  10. Effects of antipsychotic drugs on brain and behavior
    FRANK TARAZI; Fiscal Year: 2005
    ..adult rats, and should evolve new principles for improved treatments for childhood-onset schizophrenia and other major pediatric psychiatric disorders. ..
  11. Novel pharmacotherapies for treatment of ADHD
    FRANK TARAZI; Fiscal Year: 2003
    ..Expected findings should evolve new principles and lead to novel compounds that can be used as much-needed innovative treatments for ADHD and other major neuropsychiatric disorders. ..
  12. Hybrid Drugs: Novel Pharmacotherapy for ADHD
    FRANK TARAZI; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  13. Norepinephrine Transporters: Targets for ADHD
    FRANK TARAZI; Fiscal Year: 2004
    ..Expected findings should lead to novel compounds that can be developed as much needed innovative non-stimulant treatments for ADHD and other major neuropsychiatric disorders. ..
  14. CHEMICAL SYNTHESIS OF NOVEL NATURAL PRODUCTS
    David Williams; Fiscal Year: 2009
    ..Daphnicyclidin A. This recent discovery has revealed a new molecular architecture which exhibits significant antitumor activity. Our research will investigate strategies for chemical synthesis of these complex polycyclic systems. ..
  15. INTERESTING BIOACTIVE SUBSTANCES
    David Williams; Fiscal Year: 2006
    ..The selective synthesis of contiguous stereotriads will advance basic methodology for asymmetric conjugate additions. ..
  16. SYNTHESIS OF NATURAL PRODUCTS WITH OXAZOLE MOIETIES
    Peter Wipf; Fiscal Year: 2005
    ..The proposed program represents a multi-dimensional effort to increase the basic knowledge of the function of marine natural products, establish new methods in heterocyclic chemistry, and identify novel pharmacophores. ..
  17. Transdisciplinary Imaging Genetics Center (1 of 2)(RMI)
    Steven Potkin; Fiscal Year: 2006
    ..The new knowledge generated by the Center holds considerable promise for improving diagnosis and treatment of mental illness. [unreadable] [unreadable]..
  18. CYTOTOXIC NITROGEN HETEROCYCLES
    Edwin Vedejs; Fiscal Year: 2008
    ..abstract_text> ..
  19. Rapid Fluorous Synthesis of Drug-Like Small Molecules
    Wei Zhang; Fiscal Year: 2005
    ....
  20. HETEROCYCLIC RING COMPOUNDS FOR ALKALOID SYNTHESIS
    Albert Padwa; Fiscal Year: 2007
    ..The generation of biologically active compounds by new synthetic methods remains an important part of both health related and chemical research. ..
  21. Tandem Cycloaddition Chemistry of 2-Azoniaheterodienes
    SCOTT DENMARK; Fiscal Year: 2007
    ..abstract_text> ..
  22. Alkynyliodonium Salts and Derived Diyls in Synthesis
    Ken Feldman; Fiscal Year: 2009
    ..abstract_text> ..
  23. Does SIRT1 regulate mammalian health and longevity?
    JOSEPH BAUR; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  24. Cross-Coupling Reactions of Organosilanols
    SCOTT DENMARK; Fiscal Year: 2009
    ..Synthetic approaches to isodomoic acid H, hepatitis C viral inihibiting indole alkaloids, the salicylihalimide macrolactone oximidine II, and polyene antiviral antibiotic viridenomycin are detailed. ..
  25. New Methodology for Indole Alkaloid Syntheses
    Ken S Feldman; Fiscal Year: 2010
    ..The use of a new variant of the Pummerer reaction to control both oxidation level and reaction site within the indole nucleus forms the basis of this chemistry. ..
  26. ASYMMETRIC SYNTHESIS OF ANTITUMOR AGENTS
    MICHAEL CRIMMINS; Fiscal Year: 2005
    ..Laulimalide stimulates tubulin polymerization more effectively than paclitaxel. Laulimalide is a representative of a new class of microtubule stabilizing agents with promise for therapeutic potential. ..
  27. Solution Phase Libraries by Fluorous Mixture Synthesis
    Wei Zhang; Fiscal Year: 2002
    ..The company plans to use the techniques in- house for contract library synthesis and to make them available to the community at large. ..
  28. SYNTHESIS OF FUSED HETEROCYCLIC COMPOUNDS
    Albert Padwa; Fiscal Year: 2002
    ..The generation of biologically active compounds by new synthetic methods remains an important part of both health related and chemical research. ..
  29. ASYMMETRIC SYNTHESIS OF NOVEL NATURAL PRODUCTS
    MICHAEL CRIMMINS; Fiscal Year: 2006
    ..Synthesis of the biologically active agents guanacastepene, and SCH 351448 will also be pursued. ..
  30. Chemical and Biological Studies on Biaryl Phenolics
    Ken Feldman; Fiscal Year: 2005
    ..The search for selective 20S proteosome inhibitors among the Ntn-type proteases will be advanced by these investigations. ..
  31. Micromass LCT Mass Spectrometer
    MICHAEL CRIMMINS; Fiscal Year: 2004
    ..The major users group is highly dependent on rapid turn around mass spectral data. Since there is currently no Departmental mass spectrometry facility, the research programs of the major users have been seriously hampered for some time. ..
  32. PROSPECTIVE STUDY OF TARDIVE DYSKINESIA DEVELOPMENT
    John Kane; Fiscal Year: 2001
    ..This strategy will provide a rapid and cost-effective answer to a critical question. ..
  33. Synthesis of Macrolides, Steroids, Cyclopentanoids, etc.
    BARRY TROST; Fiscal Year: 2009
    ..These new synthetic methods apply to many structural types beyond those illustrated and constitutes a significant to gain access to complex molecular targets more easily. ..
  34. Functional active-site models of cytochrome c oxidase
    JAMES COLLMAN; Fiscal Year: 2009
    ..The role that the copper ion (CuB) and a phenolic group, in the amino acid tyrosine (Tyr244) play in the catalytic function of CcO are of particular interest. ..
  35. Oxidative Coupling in Natural Product Synthesis
    Phil Baran; Fiscal Year: 2009
    ....
  36. Inhibition of Alzheimer's Beta-Amyloid Fibril Formation
    Duy Hua; Fiscal Year: 2009
    ..However, soluble oligomeric Abeta showed high neuronal toxicity. Inhibition of the formation of these toxic soluble Abeta oligomers would provide therapeutics for AD. ..
  37. SYNTHESIS OF BIOACTIVE MACROLIDES
    James White; Fiscal Year: 2002
    ..These pathways, regardless of whether they are successful, must also serve as paradigms for accessing other potentially useful chemotherapeutic agents of equal or greater complexity. ..
  38. Clozapine Treatment of Schizophrenic Patients
    Robert Buchanan; Fiscal Year: 2006
    ..The study will provide new information on the clinical utility of adjunctive risperidone in treatment-resistant patients who fail to adequately respond to clozapine. ..
  39. Synthesis of Polyketides and Terpenes
    David A Evans; Fiscal Year: 2010
    ..As a consequence, organic synthesis is a critical discipline that continues to have an important impact on the fields of both medicine and biology. ..
  40. Oligopyrrole-based Anion Binding Agents
    Jonathan L Sessler; Fiscal Year: 2010
    ..abstract_text> ..
  41. 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. ..
  42. 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. ..
  43. Molecular Targets of Novel Antifungal Compounds
    Ameeta Agarwal; Fiscal Year: 2008
    ..This work will provide a starting point in the development of new antifungal therapies. [unreadable] [unreadable] [unreadable]..
  44. The Effects of the Cannabinoid-1 Receptor Antagonist Rimonabant on Weight...
    Robert Buchanan; Fiscal Year: 2008
    ..There should be direct evidence of efficacy and safety in these patients in order to provide truly effective treatments and further understanding of these disorders. [unreadable] [unreadable] [unreadable]..
  45. The 7th International Conference on Head and Neck Cancer
    Jeffrey Myers; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  46. SYNTHESIS OF BIOACTIVE ALKALOIDS
    James White; Fiscal Year: 2006
    ..A plan is presented for the synthesis of this complex heptacyclic molecule which envisions a thio-Claisen rearrangement as the key step for building the vicinal quaternary carbons of this structure. ..
  47. ASYMMETRIC SYNTHESIS OF IONOPHORE/MACROLIDE ANTIBIOTICS
    David Evans; Fiscal Year: 2005
    ..Our goal has been to set in place all of the reactions necessary for the rapid assemblage of any polyketide target structure. ..
  48. 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. ..
  49. PHYSIOLOGICALLY ACTIVE NATURAL PRODUCTS
    Douglass Taber; Fiscal Year: 2007
    ..In the course of these investigations, new molecular reactivity will be developed that will substantially shorten current routes to polycyclic natural products and drug candidates. ..
  50. Pharmacotherapy for Minor Depression
    Robert Howland; Fiscal Year: 2004
    ..The results of this study will have profound public health implications by improving our understanding of the efficacy of SJW and standard antidepressants for the treatment of MinorD. ..
  51. Changes in nicotinic receptors in parkinsonian animals
    JENNIFER KULAK; Fiscal Year: 2004
    ..abstract_text> ..
  52. Purification of Oligonucleotides and Nucleoside Triphosphates
    William Pearson; Fiscal Year: 2007
    ..The proposed work seeks to further develop an entirely new method for oligonucleotide purification, thus streamlining the development and production of these crucial substances. [unreadable] [unreadable] [unreadable]..
  53. Advanced Centers for Interventions and Services Research
    Robert Buchanan; Fiscal Year: 2007
    ....
  54. ASYMMETRIC SYNTHESIS OF VANCOMYCIN ANTIBIOTICS
    David Evans; Fiscal Year: 2001
    ..During the course of this project we intend to confirm (correct) the absolute stereochemical assignments of the principal members of this family by total synthesis. ..
  55. Medicinal Inorganic Chemistry ACS Symposium F-2003
    Jonathan Sessler; Fiscal Year: 2003
    ..It is thus expected that the present MIC-ACS symposium will afford a unique opportunity to develop further growth in a field of study that is rich in opportunity and central to the NIH mission. ..
  56. Biomimetic Studies of NO-binding Respiratory Chain Hemes
    JAMES COLLMAN; Fiscal Year: 2008
    ..An emphasis will be placed on kinetic and mechanistic studies to elucidate the putitive reaction pathways of CcO and NOR. ..
  57. New Synthetic Routes to Phorbols and Ingananes
    TIMO OVASKA; Fiscal Year: 2003
    ..This basic ring construction strategy will be coupled with other synthetic methodologies to generate structurally and functionally diverse analogues of phorbol and ingenol. ..
  58. CATCH: Mechanochemistry and Regulation in Smooth Muscle
    Thomas Butler; Fiscal Year: 2008
    ..4) Determination of the extent of involvement of myosin crossbridges in catch force maintenance by measurements of changes in orientation of fluorescent probes attached to the regulatory light chain. ..
  59. Total Synthesis of Anti-Cancer Natural Products
    Phil S Baran; Fiscal Year: 2010
    ..New strategies and methods in chemistry and substantial contributions to medicine are anticipated through strategic collaborations with several leaders in the field of cancer biology. ..