isoquinolines

Summary

Summary: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)

Top Publications

  1. ncbi In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease
    Alexander Gerhard
    MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, London, UK
    Neurobiol Dis 21:404-12. 2006
  2. ncbi Sanguinarine induces apoptosis of HT-29 human colon cancer cells via the regulation of Bax/Bcl-2 ratio and caspase-9-dependent pathway
    Jun Sik Lee
    Heart Research Center of Chonnam National University Hospital, Cardiovascular Research Institute of Chonnam National University, Gwangju 501 757, Korea
    Int J Toxicol 31:70-7. 2012
  3. ncbi In-vivo measurement of activated microglia in dementia
    A Cagnin
    MRC Cyclotron Unit, Imperial College, Faculty of Medicine, Division of Neuroscience and Psychological Medicince, Hammersmith Hospital, London, UK
    Lancet 358:461-7. 2001
  4. ncbi Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron
    Peter Eisenberg
    California Cancer Care, Greenbrae, California, USA
    Cancer 98:2473-82. 2003
  5. pmc Mixed-affinity binding in humans with 18-kDa translocator protein ligands
    David R J Owen
    Division of Experimental Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
    J Nucl Med 52:24-32. 2011
  6. pmc 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
  7. ncbi Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor
    Camilo Rojas
    Research and Translational Development, MGI PHARMA INC, 6611 Tributary St, Baltimore, MD 21224 6515, USA
    Anesth Analg 107:469-78. 2008
  8. ncbi Evaluation of anticancer activities of benzo[c]phenanthridine alkaloid sanguinarine in oral squamous cell carcinoma cell line
    Hikari Tsukamoto
    Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Ota ku, Tokyo, Japan
    Anticancer Res 31:2841-6. 2011
  9. ncbi Sanguinarine induces apoptosis of human osteosarcoma cells through the extrinsic and intrinsic pathways
    Hyunjin Park
    Cell Biomaterial Biohybrid Systems, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1
    Biochem Biophys Res Commun 399:446-51. 2010
  10. ncbi Reference and target region modeling of [11C]-(R)-PK11195 brain studies
    Federico E Turkheimer
    Division of Neuroscience, Department of Clinical Neuroscience, Imperial College London, London, United Kingdom
    J Nucl Med 48:158-67. 2007

Detail Information

Publications340 found, 100 shown here

  1. ncbi In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease
    Alexander Gerhard
    MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, London, UK
    Neurobiol Dis 21:404-12. 2006
    ..The absence of significant longitudinal changes suggests that microglia are activated early in the disease process, and levels then remain relatively static, possibly driving the disease via cytokine release...
  2. ncbi Sanguinarine induces apoptosis of HT-29 human colon cancer cells via the regulation of Bax/Bcl-2 ratio and caspase-9-dependent pathway
    Jun Sik Lee
    Heart Research Center of Chonnam National University Hospital, Cardiovascular Research Institute of Chonnam National University, Gwangju 501 757, Korea
    Int J Toxicol 31:70-7. 2012
    ..Our results suggest that sanguinarine induces apoptosis of HT-29 human colon cancer cells and may have a potential therapeutic use in the treatment of human colon cancer...
  3. ncbi In-vivo measurement of activated microglia in dementia
    A Cagnin
    MRC Cyclotron Unit, Imperial College, Faculty of Medicine, Division of Neuroscience and Psychological Medicince, Hammersmith Hospital, London, UK
    Lancet 358:461-7. 2001
    ..INTERPRETATION: In-vivo detection of increased [11C](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that microglial activation is an early event in the pathogenesis of the disease...
  4. ncbi Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron
    Peter Eisenberg
    California Cancer Care, Greenbrae, California, USA
    Cancer 98:2473-82. 2003
    ..The current Phase III trial evaluated the efficacy and safety of palonosetron in preventing acute and delayed CINV after moderately emetogenic chemotherapy...
  5. pmc Mixed-affinity binding in humans with 18-kDa translocator protein ligands
    David R J Owen
    Division of Experimental Medicine, Imperial College, Hammersmith Hospital, London, United Kingdom
    J Nucl Med 52:24-32. 2011
    ....
  6. pmc 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...
  7. ncbi Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor
    Camilo Rojas
    Research and Translational Development, MGI PHARMA INC, 6611 Tributary St, Baltimore, MD 21224 6515, USA
    Anesth Analg 107:469-78. 2008
    ..However, these attributes alone are not sufficient to explain the results with palonosetron. We sought to elucidate additional differences among 5-HT(3)-RAs that could help explain the observations in the clinic...
  8. ncbi Evaluation of anticancer activities of benzo[c]phenanthridine alkaloid sanguinarine in oral squamous cell carcinoma cell line
    Hikari Tsukamoto
    Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Ota ku, Tokyo, Japan
    Anticancer Res 31:2841-6. 2011
    ..Taken together, these results indicate that sanguinarine is a potential inhibitor of tumorigenesis and suggest that it may be valuable in the development of new anticancer drugs for the treatment of OSCC...
  9. ncbi Sanguinarine induces apoptosis of human osteosarcoma cells through the extrinsic and intrinsic pathways
    Hyunjin Park
    Cell Biomaterial Biohybrid Systems, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1
    Biochem Biophys Res Commun 399:446-51. 2010
    ..It activated multicaspases, and increased the activities of caspase-8 and caspase-9 in both MG-63 and SaOS-2 cells. These data highlight sanguinarine as a novel potential agent for bone cancer therapy...
  10. ncbi Reference and target region modeling of [11C]-(R)-PK11195 brain studies
    Federico E Turkheimer
    Division of Neuroscience, Department of Clinical Neuroscience, Imperial College London, London, United Kingdom
    J Nucl Med 48:158-67. 2007
    ....
  11. ncbi Development of a tracer kinetic plasma input model for (R)-[11C]PK11195 brain studies
    Marc A Kropholler
    Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, The Netherlands
    J Cereb Blood Flow Metab 25:842-51. 2005
    ..It was concluded that a two-tissue reversible compartment model with K(1)/k(2) fixed to whole cortex value is optimal for analyzing (R)-[(11)C]PK11195 PET brain studies...
  12. ncbi Promotion of sleep by targeting the orexin system in rats, dogs and humans
    Catherine Brisbare-Roch
    Research and Development, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH 4123 Allschwil, Switzerland
    Nat Med 13:150-5. 2007
    ..No signs of cataplexy were observed, in contrast to the rodent, dog or human narcolepsy syndromes. These results open new perspectives for investigating the role of endogenous orexins in sleep-wake regulation...
  13. ncbi Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function
    Camilo Rojas
    Johns Hopkins University School of Medicine, Brain Science Institute Neurotranslational Center, 6611 Tributary Street, Baltimore, MD 21224 6515, USA
    Eur J Pharmacol 626:193-9. 2010
    ..These experiments may provide a pharmacological basis for differences noted in published clinical trials comparing palonosetron to other 5-HT(3) receptor antagonists...
  14. ncbi The many faces of H89: a review
    A Lochner
    Dept Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa
    Cardiovasc Drug Rev 24:261-74. 2006
    ..H-89 should be used in conjunction with other PKA inhibitors, such as Rp-cAMPS or PKA analogs...
  15. ncbi Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair
    Y Takebayashi
    Laboratory of Molecular Pharmacology, National Cancer Institute/NIH, Bethesda, Maryland, USA
    Nat Med 7:961-6. 2001
    ..We found that Et743 interacts with the transcription-coupled NER machinery to induce lethal DNA strand breaks...
  16. ncbi Imaging microglial activation in Huntington's disease
    Yen F Tai
    Division of Neuroscience and Psychological Medicine, Hammersmith Hospital, Imperial College London, UK
    Brain Res Bull 72:148-51. 2007
    ..Further longitudinal studies are needed to fully elucidate this link...
  17. ncbi Evolution of microglial activation in patients after ischemic stroke: a [11C](R)-PK11195 PET study
    Alexander Gerhard
    MRC Clinical Sciences Centre and Department of Neuropathology, Faculty of Medicine, Imperial College, London, UK
    Neuroimage 24:591-5. 2005
    ..Our data suggest that [11C](R)-PK11195 PET can be used to investigate both the primary lesion and remote pathological changes following Wallerian degeneration...
  18. ncbi Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex
    Bart L Staker
    deCODE BioStructures, 7869 NE Day Road West, Bainbridge Island, Washington 98110, USA
    J Med Chem 48:2336-45. 2005
    ..These new X-ray structures explain how very different molecules can stabilize top1-DNA covalent complexes and will aid the rational design of completely novel structural classes of anticancer drugs...
  19. ncbi A randomized, double-blind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo for preventing postoperative nausea and vomiting
    Keith A Candiotti
    Department of Anesthesiology, University of Miami, Miami, Florida, USA
    Anesth Analg 107:445-51. 2008
    ....
  20. pmc Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial
    Luigi Celio
    Medical Oncology Unit 2, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
    Support Care Cancer 19:1217-25. 2011
    ....
  21. ncbi Hypocretin/orexin contributes to the expression of some but not all forms of stress and arousal
    Teri M Furlong
    School of Medical Sciences, University of New South Wales, NSW 2052, Australia
    Eur J Neurosci 30:1603-14. 2009
    ..When it does, hypocretin will at least contribute to the cardiovascular response. The findings are of clinical relevance to some forms of psychological stress...
  22. ncbi Sanguinarine sensitizes human gastric adenocarcinoma AGS cells to TRAIL-mediated apoptosis via down-regulation of AKT and activation of caspase-3
    Woo Young Choi
    Department of Biochemistry, Dongeui University College of Oriental Medicine, Yangjung Dong, Busanjin Gu, Busan 614 714, South Korea
    Anticancer Res 29:4457-65. 2009
    ....
  23. pmc Isolation of the mitochondrial benzodiazepine receptor: association with the voltage-dependent anion channel and the adenine nucleotide carrier
    M W McEnery
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205 2185
    Proc Natl Acad Sci U S A 89:3170-4. 1992
    ..VDAC and ADC, outer and inner mitochondrial membrane channel proteins, respectively, together with the 18-kDa subunit, may comprise mBzR at functionally important transport sites at the junction of two mitochondrial membranes...
  24. ncbi 18F-FEAC and 18F-FEDAC: PET of the monkey brain and imaging of translocator protein (18 kDa) in the infarcted rat brain
    Joji Yui
    Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan
    J Nucl Med 51:1301-9. 2010
    ....
  25. ncbi Acute effect of palonosetron on electrocardiographic parameters in cancer patients: a prospective study
    C Yavas
    Department of Radiation Oncology, Konya Training and Research Hospital, Konya, Turkey
    Support Care Cancer 20:2343-7. 2012
    ..The acute cardiac effect of palonosteron is unknown. The purpose of this study is to determine acute effects of palonosetron on electrocardiographic (ECG) parameters in cancer patients...
  26. pmc The interaction of RS 25259-197, a potent and selective antagonist, with 5-HT3 receptors, in vitro
    E H Wong
    Institute of Pharmacology, Palo Alto, California 94303, USA
    Br J Pharmacol 114:851-9. 1995
    1. A series of isoquinolines have been identified as 5-HT3 receptor antagonists. One of these, RS 25259-197 [(3aS)-2-[(S)-1-azabicyclo[2.2...
  27. ncbi Imaging glial cell activation with [11C]-R-PK11195 in patients with AIDS
    Dima A Hammoud
    Department of Radiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287 2182, USA
    J Neurovirol 11:346-55. 2005
    ..The findings of this pilot study support a role for glial cell activation in HAD, and that PET with [11C]-R-PK11195 can detect the concomitants of neuronal damage in individuals infected with HIV...
  28. ncbi Peripheral benzodiazepine receptor ligands reverse apoptosis resistance of cancer cells in vitro and in vivo
    Didier Decaudin
    Department of Hematology, and UMR 147 CNRS, Section de Recherche, Institut Curie, 75005 Paris, France
    Cancer Res 62:1388-93. 2002
    ..Peripheral benzodiazepine receptor ligands may therefore act as chemosensitizing agents for the treatment of human neoplasms...
  29. ncbi DNA-binding affinities and sequence selectivity of quaternary benzophenanthridine alkaloids sanguinarine, chelerythrine, and nitidine
    Li Ping Bai
    School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong
    Bioorg Med Chem 14:5439-45. 2006
    ....
  30. pmc The positron emission tomography ligand DAA1106 binds with high affinity to activated microglia in human neurological disorders
    Sriram Venneti
    Department of Pathology, University of Pittsburgh School of Medicine, and Presbyterian University Hospital, Neuropathology Division, Pittsburgh, Pennsylvania 15213, USA
    J Neuropathol Exp Neurol 67:1001-10. 2008
    ....
  31. ncbi Palonosetron: in the prevention of nausea and vomiting
    Lily P H Yang
    Adis, North Shore, Auckland, New Zealand
    Drugs 69:2257-78. 2009
    ..Intravenous palonosetron is a useful alternative to currently recommended agents in PONV prevention...
  32. pmc An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28
    David R Owen
    Division of Experimental Medicine, Department of Medicine, Imperial College London, Hammersmith Hospital, London, UK
    J Cereb Blood Flow Metab 32:1-5. 2012
    ....
  33. ncbi In vivo imaging of microglial activation with [11C](R)-PK11195 PET in corticobasal degeneration
    Alexander Gerhard
    MRC Clinical Sciences Center and Division of Neuroscience, Faculty of Medicine, Imperial College, London, United Kingdom
    Mov Disord 19:1221-6. 2004
    ....
  34. pmc Developmental regulation of protein kinase A expression and activity in Schistosoma mansoni
    Brett E Swierczewski
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
    Int J Parasitol 40:929-35. 2010
    ..Taken together, our data suggest that PKA signalling is required for cercarial viability and may play a specific role in the reproductive activity of adult worms...
  35. pmc Inhibition of Stat3 activation by sanguinarine suppresses prostate cancer cell growth and invasion
    Meng Sun
    Department of Urology, University of California at Davis, Sacramento, California, USA
    Prostate 72:82-9. 2012
    ..Sanguinarine, a benzophenanthridine alkaloid derived primarily from the bloodroot plant, was identified previously as a novel inhibitor of survivin that selectively kills prostate cancer cells over "normal" prostate epithelial cells...
  36. ncbi [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy
    A Gerhard
    MRC Clinical Sciences Center and Division of Neuroscience, Faculty of Medicine, Imperial College, London, UK
    Neurology 61:686-9. 2003
    ..Providing an indicator of disease activity, [11C](R)-PK11195 PET can thus be used to characterize the in vivo neuropathology of MSA...
  37. ncbi Inhibition of lipopolysaccharide-induced cyclooxygenase-2, tumor necrosis factor-alpha and [Ca2+]i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195
    Hyan B Choi
    Department of Pharmacology and Therapeutics, Division of Neurology, Faculty of Medicine, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3
    J Neurochem 83:546-55. 2002
    ....
  38. ncbi Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial
    Mitsue Saito
    Department of Breast Oncology, Juntendo University Hospital, Tokyo, Japan
    Lancet Oncol 10:115-24. 2009
    ....
  39. ncbi Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation
    Fabien Chauveau
    CEA, DSV, I2BM, LIME, Orsay, France
    J Nucl Med 50:468-76. 2009
    ....
  40. ncbi Double-blind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy
    M Aapro
    Division of Oncology, Institut Multidisciplinaire d Oncologie, Clinique de Genolier, Genolier, Switzerland
    Ann Oncol 21:1083-8. 2010
    ..We evaluated the possibility to reduce the total dose of corticosteroids when palonosetron, a long-acting second-generation 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, is used...
  41. ncbi Novel indenoisoquinolines NSC 725776 and NSC 724998 produce persistent topoisomerase I cleavage complexes and overcome multidrug resistance
    Smitha Antony
    Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, MD 20892 4255, USA
    Cancer Res 67:10397-405. 2007
    ..These gamma-H2AX foci were detectable at pharmacologically relevant doses for up to 24 h and thus could be used as biomarkers for clinical trials (phase 0)...
  42. ncbi Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats
    Santiago Rojas
    Department of Brain Ischemia and Neurodegeneration, Institut d Investigacions Biomèdiques de Barcelona IIBB Consejo Superior de Investigaciones Científicas CSIC, Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, Barcelona, Spain
    J Cereb Blood Flow Metab 27:1975-86. 2007
    ..These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding depends on intrinsic features of the inflammatory cells...
  43. pmc Altered subcellular distribution of MSK1 induced by glucocorticoids contributes to NF-kappaB inhibition
    Ilse M E Beck
    Laboratory of Eukaryotic Gene Expression and Signal Transduction, Department of Molecular Biology, Gent University, Gent, Belgium
    EMBO J 27:1682-93. 2008
    ..These findings unveil a novel aspect within the GR-mediated NF-kappaB-targeting anti-inflammatory mechanism...
  44. ncbi Evaluation of methods for generating parametric (R-[11C]PK11195 binding images
    Alie Schuitemaker
    Department of Nuclear Medicine and PET Research, VU University Medical Centre, Amsterdam, The Netherlands
    J Cereb Blood Flow Metab 27:1603-15. 2007
    ..In pathological conditions with reduced flow rates or large variations in blood volume, the basis function method is preferred because it produces less bias and is more precise...
  45. ncbi Involvement of benzodiazepine receptors in neuroinflammatory and neurodegenerative diseases: evidence from activated microglial cells in vitro
    H Wilms
    Klinik fur Neurologie, Christian Albrechts Universitat zu Kiel, Niemannsweg 147, 24105 Kiel, Germany
    Neurobiol Dis 14:417-24. 2003
    ..These findings link the in vivo data of elevated PBR levels in neurodegenerative/-inflammatory diseases to a functional role and opens up possible therapeutic intervention targeting the PBR in microglia...
  46. ncbi Sanguinarine-dependent induction of apoptosis in primary effusion lymphoma cells
    Azhar R Hussain
    Human Cancer Genomic Research, King Fahad National Center for Children s Cancer and Research, Biological and Medical Research, Riyadh 11211, Saudi Arabia
    Cancer Res 67:3888-97. 2007
    ....
  47. ncbi Novel reference region model reveals increased microglial and reduced vascular binding of 11C-(R)-PK11195 in patients with Alzheimer's disease
    Giampaolo Tomasi
    Department of Information Engineering, University of Padova, Padova, Italy
    J Nucl Med 49:1249-56. 2008
    ....
  48. ncbi Visualising microglial activation in vivo
    Richard B Banati
    Department of Neuropathology, Charing Cross Hospital, Imperial College School of Medicine, and MRC Clinical Sciences Centre PET Neurology, Hammersmith Hospital, London, United Kingdom
    Glia 40:206-17. 2002
    ....
  49. ncbi Blockade of orexin-1 receptors attenuates orexin-2 receptor antagonism-induced sleep promotion in the rat
    Christine Dugovic
    Neuroscience, Johnson and Johnson PRD, 3210 Merryfield Row, San Diego, CA 92121, USA
    J Pharmacol Exp Ther 330:142-51. 2009
    ..In addition, it is suggested that simultaneous inhibition of OX1R attenuates the sleep-promoting effects mediated by selective OX2R blockade, possibly correlated with dopaminergic neurotransmission...
  50. pmc [11C]-DPA-713 and [18F]-DPA-714 as new PET tracers for TSPO: a comparison with [11C]-(R)-PK11195 in a rat model of herpes encephalitis
    Janine Doorduin
    Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
    Mol Imaging Biol 11:386-98. 2009
    ..In this study, we evaluated the PET tracers [(11)C]-DPA-713 and [(18)F]-DPA-714 as agents for imaging of activated microglia in a rat model of herpes encephalitis...
  51. pmc The indenoisoquinoline noncamptothecin topoisomerase I inhibitors: update and perspectives
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Mol Cancer Ther 8:1008-14. 2009
    ..We discuss the use of γ-H2AX as a pharmacodynamic biomarker for the clinical development of the indenoisoquinolines...
  52. pmc Synthesis of substituted isoquinolines utilizing palladium-catalyzed α-arylation of ketones
    Timothy J Donohoe
    Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, United Kingdom
    Proc Natl Acad Sci U S A 109:11605-8. 2012
    ..palladium-catalyzed α-arylation and cyclization reactions provides a general approach to an array of isoquinolines and their corresponding N-oxides...
  53. ncbi Differential induction of topoisomerase I-DNA cleavage complexes by the indenoisoquinoline MJ-III-65 (NSC 706744) and camptothecin: base sequence analysis and activity against camptothecin-resistant topoisomerases I
    Smitha Antony
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute NIH, 37 Convent Drive, Bethesda, MD 20892 4255, USA
    Cancer Res 63:7428-35. 2003
    ..This study shows the specific molecular interactions of MJ-III-65 with top1 and demonstrates that MJ-III-65 is a potentially useful top1 inhibitor that enhances and traps top1 cleavage sites not sensitive to CPTs...
  54. ncbi Isoquinoline synthesis via rhodium-catalyzed oxidative cross-coupling/cyclization of aryl aldimines and alkynes
    Nicolas Guimond
    Centre for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Canada K1N 6N5
    J Am Chem Soc 131:12050-1. 2009
    ..This process affords 3,4-disubstituted isoquinolines in good yield and high regioselectivity...
  55. pmc Agonists and antagonists induce different palonosetron dissociation rates in 5-HT₃A and 5-HT₃AB receptors
    Sarah C R Lummis
    Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK
    Neuropharmacology 73:241-6. 2013
    ....
  56. ncbi On the binding of indeno[1,2-c]isoquinolines in the DNA-topoisomerase I cleavage complex
    Xiangshu Xiao
    Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Cancer Center, School of Pharmacy and Pharmaceutical Sciences, Purdue University, West Lafayette, Indiana 47907, USA
    J Med Chem 48:3231-8. 2005
    ....
  57. pmc Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[(11)C]PK11195 brain PET studies
    Maqsood Yaqub
    Department of Nuclear Medicine and PET Research, VU University Medical Center, Amsterdam, The Netherlands
    J Cereb Blood Flow Metab 32:1600-8. 2012
    ..Incorporation of V(b) within RPM, together with SVCA4, appears to be the method of choice for analyzing cerebral (R)-[(11)C]PK11195 neurodegeneration studies...
  58. ncbi Salsolinol, a tetrahydroisoquinoline-derived neurotoxin, induces oxidative modification of neurofilament-L protection by histidyl dipeptides
    Jung Hoon Kang
    Department of Genetic Engineering, Cheongju University, Cheongju 360 764, Korea
    BMB Rep 45:114-9. 2012
    ..Both compounds also inhibited the generation of •OH induced by salsolinol. The results indicated that carnosine and related compounds may prevent salsolinol-mediated NF-L modification via free radical scavenging...
  59. ncbi Orexins depolarize rostral ventrolateral medulla neurons and increase arterial pressure and heart rate in rats mainly via orexin 2 receptors
    Shang Cheng Huang
    Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
    J Pharmacol Exp Ther 334:522-9. 2010
    ..We concluded that orexins directly excite RVLM neurons, which include bulbospinal vasomotor neurons, and regulate cardiovascular function mainly via the OX(2)R, with a smaller contribution from the OX(1)R...
  60. ncbi Efficacy of palonosetron (PAL) compared to other serotonin inhibitors (5-HT3R) in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetogenic (MoHE) treatment: systematic review and meta-analysis
    Tobias Engel Ayer Botrel
    Rua Tranquillo Prosperi, 143, Campinas, Sao Paulo, 13084 778, Brazil
    Support Care Cancer 19:823-32. 2011
    ..25 mg with other 5-HT(3)R in patients receiving moderately or highly emetogenic (MoHE) chemotherapy...
  61. pmc The binding orientation of a norindenoisoquinoline in the topoisomerase I-DNA cleavage complex is primarily governed by pi-pi stacking interactions
    Yunlong Song
    Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue Cancer Center, Purdue University, West Lafayette, IN 47907, USA
    J Phys Chem B 112:9484-9. 2008
    ....
  62. pmc The antiemetic 5-HT3 receptor antagonist Palonosetron inhibits substance P-mediated responses in vitro and in vivo
    Camilo Rojas
    the Brain Science Institute, Johns Hopkins University School of Medicine, 855 N Wolfe Street, Suite 270, Baltimore, MD 21205, USA
    J Pharmacol Exp Ther 335:362-8. 2010
    ....
  63. ncbi TSPO over-expression increases motility, transmigration and proliferation properties of C6 rat glioma cells
    Mariarosa Rechichi
    Dipartimento di Morfologia Umana e Biologia Applicata, University of Pisa, Via Volta 4, Pisa, Italy
    Biochim Biophys Acta 1782:118-25. 2008
    ..These findings suggest that the use of TSPO ligands as chemotherapeutic agents could be effective on aggressive tumor cells with a high TSPO expression level...
  64. ncbi The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells
    Antonio F Santidrian
    Departament de Ciències Fisiològiques II, IDIBELL Universitat de Barcelona, L Hospitalet de Llobregat, Spain
    Haematologica 92:1631-8. 2007
    ..Primary chronic lymphocytic leukemia (CLL) cells overexpress TSPO. The aim of this study was to examine the effects of PK11195 on CLL cells. Table 1. Characteristics of the patients with chronic lymphocytic leukemia...
  65. ncbi Inhibition of poly adenosine diphosphate-ribose polymerase decreases hepatocellular carcinoma growth by modulation of tumor-related gene expression
    Rosa Quiles-Perez
    San Cecilio University Hospital, Granada, Spain
    Hepatology 51:255-66. 2010
    ..05)...
  66. ncbi SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods
    Alie Schuitemaker
    Department of Nuclear Medicine and PET Research, VU University Medical Centre, P O Box 7057, 1081 MB Amsterdam, The Netherlands
    Neuroimage 35:1473-9. 2007
    ..Vd images could only demonstrate differences in (R)-[11C]PK11195 binding when analysed with proportional scaling due to intersubject variation in K1/k2 (blood-brain barrier transport and non-specific binding)...
  67. ncbi Widespread and prolonged increase in (R)-(11)C-PK11195 binding after traumatic brain injury
    Hedy Folkersma
    Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands
    J Nucl Med 52:1235-9. 2011
    ..Our objective was to measure (R)-(11)C-PK11195 binding as an indirect marker of neuronal damage after traumatic brain injury (TBI)...
  68. pmc Identification of SR8278, a synthetic antagonist of the nuclear heme receptor REV-ERB
    Douglas Kojetin
    ACS Chem Biol 6:131-4. 2011
    ..Thus, SR8278 represents a unique chemical tool for probing REV-ERB function and may serve as a point for initiation of further optimization to develop REV-ERB antagonists with the ability to explore circadian and metabolic functions...
  69. ncbi Design, synthesis, and biological evaluation of a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones as dual inhibitors of human immunodeficiency virus type 1 integrase and the reverse transcriptase RNase H domain
    Muriel Billamboz
    Laboratoire de Chimie Organique et Macromoléculaire, UMR CNRS 8009, Universite de Lille 1, 59655 Villeneuve d Ascq, France
    J Med Chem 51:7717-30. 2008
    ..Unfortunately, all tested compounds exhibited high cellular cytotoxicity in cell culture which limits their applications as antiviral agents...
  70. ncbi Salsolinol produces reinforcing effects in the nucleus accumbens shell of alcohol-preferring (P) rats
    Zachary A Rodd
    Indiana University School of Medicine, Institute of Psychiatric Research, 791 Union Drive, Indianapolis, IN 46202 4887, USA
    Alcohol Clin Exp Res 27:440-9. 2003
    ....
  71. ncbi ET-743: the US experience in sarcomas of soft tissues
    George D Demetri
    Center for Sarcoma and Bone Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    Anticancer Drugs 13:S7-9. 2002
    ..There were no treatment-associated deaths. In conclusion, ET-743 is an active chemotherapeutic agent that can induce objective responses and clinical benefit in a subset of patients with metastatic or advanced soft-tissue sarcoma...
  72. pmc Antisense RNA-mediated suppression of benzophenanthridine alkaloid biosynthesis in transgenic cell cultures of California poppy
    Sang Un Park
    Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada T2N 1N4
    Plant Physiol 128:696-706. 2002
    ..These data provide new insight into the metabolic engineering of benzophenanthridine alkaloid pathways...
  73. ncbi Phosphorylation of glycogen synthase kinase-3 and stimulation of T-cell factor signaling following activation of EP2 and EP4 prostanoid receptors by prostaglandin E2
    Hiromichi Fujino
    Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona 85721 0207, USA
    J Biol Chem 277:2614-9. 2002
    ..This is the first indication of a fundamental difference in the signaling potential of EP(2) and EP(4) prostanoid receptors...
  74. ncbi Novel phosphorylation of aquaporin-5 at its threonine 259 through cAMP signaling in salivary gland cells
    Takahiro Hasegawa
    Dept of Molecular Oral Physiology, Institute of Health Biosciences, The Univ of Tokushima Graduate School, Japan
    Am J Physiol Cell Physiol 301:C667-78. 2011
    ..These results suggest that AQP5 is phosphorylated at its Thr259 by PKA through cAMP, but not Ca(2+), signaling pathways, and that this phosphorylation does not contribute to AQP5 trafficking in the salivary gland cells...
  75. ncbi Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury
    R B Banati
    Peripheral Neuropathy Unit, MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, Hammersmith Hospital, London, UK
    Neuroreport 12:3439-42. 2001
    ..Our findings support the view that long-term rearrangement of cortical representational maps is significantly determined within the thalamus...
  76. ncbi Sanguinarine (pseudochelerythrine) is a potent inhibitor of NF-kappaB activation, IkappaBalpha phosphorylation, and degradation
    M M Chaturvedi
    Cytokine Research Section, Department of Molecular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 272:30129-34. 1997
    ..Overall, our results demonstrate that sanguinarine is a potent suppressor of NF-kappaB activation and it acts at a step prior to IkappaBalpha phosphorylation...
  77. pmc Differential effects of the dual orexin receptor antagonist almorexant and the GABA(A)-α1 receptor modulator zolpidem, alone or combined with ethanol, on motor performance in the rat
    Michel A Steiner
    CNS Pharmacology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland
    Neuropsychopharmacology 36:848-56. 2011
    ....
  78. ncbi Induction of conditioned place preference and dopamine release by salsolinol in posterior VTA of rats: involvement of μ-opioid receptors
    Lucía Hipólito
    Departament de Farmàcia i Tecnologia Farmacèutica, Universitat de Valencia, Avda Vicente Andres Estelles s n, 46100 Burjassot, Spain
    Neurochem Int 59:559-62. 2011
    ..The local pretreatment with β-FNA, an antagonist of MORs, prevented this increase, supporting our hypothesis on the involvement of MORs in the Sal-derived effects...
  79. ncbi Cyclooxygenase 2 rescues LNCaP prostate cancer cells from sanguinarine-induced apoptosis by a mechanism involving inhibition of nitric oxide synthase activity
    Jacob Huh
    Department of Medicine and Free Radical Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53266, USA
    Cancer Res 66:3726-36. 2006
    ....
  80. ncbi Orexin receptor antagonism, a new sleep-promoting paradigm: an ascending single-dose study with almorexant
    P Hoever
    Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland
    Clin Pharmacol Ther 87:593-600. 2010
    ..Population pharmacokinetic/pharmacodynamic modeling suggested that doses of ~500 mg almorexant and 10 mg zolpidem are equivalent with respect to subjectively assessed alertness...
  81. ncbi Positron emission tomography imaging of neuroinflammation
    Annachiara Cagnin
    Department of Neuroscience, University of Padova, Via Giustiniani 5, 35128, Padova, Italy
    Neurotherapeutics 4:443-52. 2007
    ....
  82. ncbi Anti-emetic effect of ondansetron and palonosetron in thyroidectomy: a prospective, randomized, double-blind study
    Y E Moon
    Department of Anaesthesiology and Pain Medicine, Seoul St Mary s Hospital, Catholic University College of Medicine, Seoul, Republic of Korea
    Br J Anaesth 108:417-22. 2012
    ..This study compared the effects of i.v. ondansetron and palonosetron administered at the end of surgery in preventing postoperative nausea and vomiting (PONV) in high-risk patients receiving i.v. PCA after thyroidectomy...
  83. ncbi Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist
    Rudolph M Navari
    Indiana University School of Medicine, Notre Dame Cancer Institute, South Bend, IN 46617, USA
    Future Oncol 2:591-602. 2006
    ..Future studies may consider the use of palonosetron with current and other new agents and in other clinical settings, such as bone marrow transplantation and radiation therapy...
  84. ncbi Neuropathological imaging: in vivo detection of glial activation as a measure of disease and adaptive change in the brain
    Richard B Banati
    Molecular Neuropsychiatry, Department of Neuropathology, Charing Cross Hospital, Imperial College School of Medicine, London, UK
    Br Med Bull 65:121-31. 2003
    ..Systematic attempts are now undertaken, using positron emission tomography and a ligand with relative selectivity for activated microglia, to develop generic imaging tools for a cellular in vivo neuropathology...
  85. ncbi Sanguinarine causes cell cycle blockade and apoptosis of human prostate carcinoma cells via modulation of cyclin kinase inhibitor-cyclin-cyclin-dependent kinase machinery
    Vaqar Mustafa Adhami
    Department of Dermatology, University of Wisconsin Medical Science Center, 1300 University Avenue, Madison, WI 53706, USA
    Mol Cancer Ther 3:933-40. 2004
    ..These results suggest that sanguinarine may be developed as an agent for the management of prostate cancer...
  86. ncbi PET imaging with [11C]PBR28 can localize and quantify upregulated peripheral benzodiazepine receptors associated with cerebral ischemia in rat
    Masao Imaizumi
    Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 1, Room B3 10, 1 Center Drive, MSC 0135, Bethesda, MD 20892 0135, USA
    Neurosci Lett 411:200-5. 2007
    ..In this first study to demonstrate neuroinflammation in vivo with small animal PET, [11C]PBR28 had adequate sensitivity to localize and quantify the associated increase in PBRs...
  87. ncbi Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918
    M Maliepaard
    Division of Experimental Therapy, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Clin Cancer Res 7:935-41. 2001
    ..This observation may have important clinical implications for future development of novel camptothecins...
  88. ncbi Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists
    Pari Malherbe
    F Hoffmann La Roche Ltd, Bldg 69 333, CH 4070 Basel, Switzerland
    Mol Pharmacol 76:618-31. 2009
    ..The electrophysiology data suggest that OX(2) might be more important than OX(1) in mediating the effect of orexin-A on slow-firing of VTA dopaminergic neurons...
  89. ncbi Positron emission tomography imaging of peripheral benzodiazepine receptor binding in human immunodeficiency virus-infected subjects with and without cognitive impairment
    Clayton A Wiley
    Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    J Neurovirol 12:262-71. 2006
    ....
  90. ncbi An active protein kinase A (PKA) is involved in meiotic arrest of rat growing oocytes
    Michal Kovo
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, 76100 Israel
    Reproduction 132:33-43. 2006
    ....
  91. ncbi MSK activation and physiological roles
    J Simon C Arthur
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK
    Front Biosci 13:5866-79. 2008
    ..The physiological roles of MSKs still remain to be completely determined, however recent work has suggested a role for MSKs in neuronal synaptic plasticity and in regulating cytokine production in the innate immune system...
  92. pmc Topoisomerase I levels in the NCI-60 cancer cell line panel determined by validated ELISA and microarray analysis and correlation with indenoisoquinoline sensitivity
    Thomas D Pfister
    Laboratory of Human Toxicology and Pharmacology, Applied Developmental Research Support Directorate, Science Applications International Corporation Frederick Inc, National Cancer Institute Frederick, Frederick, MD 21702, USA
    Mol Cancer Ther 8:1878-84. 2009
    ....
  93. ncbi The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases
    Rebecca L Hurley
    Departments of Medicine and Biochemistry, Dartmouth Medical School and the Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA
    J Biol Chem 280:29060-6. 2005
    ..These data indicate that the CaMKKs function in intact cells as AMPKKs, predicting wider roles for these kinases in regulating AMPK activity in vivo...
  94. ncbi Synergy of Pancratistatin and Tamoxifen on breast cancer cells in inducing apoptosis by targeting mitochondria
    Peter Siedlakowski
    Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada
    Cancer Biol Ther 7:376-84. 2008
    ....
  95. pmc Comparison of [(11)C]-(R)-PK 11195 and [(11)C]PBR28, two radioligands for translocator protein (18 kDa) in human and monkey: Implications for positron emission tomographic imaging of this inflammation biomarker
    William C Kreisl
    Molecular Imaging Branch, National Institute of Mental Health, Bethesda, MD, USA
    Neuroimage 49:2924-32. 2010
    ..This study asked two questions: (1) What is the cause of non-binding to PBR28? and (2) Why has this phenomenon not been reported using [(11)C]-(R)-PK 11195?..
  96. ncbi Palonosetron
    M Asif A Siddiqui
    Adis International Limited, Mairangi Bay, Auckland, New Zealand
    Drugs 64:1125-32; discussion 1133-4. 2004
    ..Intravenous palonosetron was generally well tolerated in clinical trials, with few adverse events being treatment related. Palonosetron had no significant effect on the corrected QT interval or laboratory parameters...
  97. ncbi Morphinans and isoquinolines: acetylcholinesterase inhibition, pharmacophore modeling, and interaction with opioid receptors
    Daniela Schuster
    Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck and Center for Molecular Biosciences Innsbruck CMBI, Innrain 52a c, A 6020 Innsbruck, Austria
    Bioorg Med Chem 18:5071-80. 2010
    ..The most active compounds were biochemically tested for their activity on mu, delta, and kappa opioid receptors...
  98. pmc Mitogen- and stress-activated kinase 1-mediated histone H3 phosphorylation is crucial for cell transformation
    Hong Gyum Kim
    The Hormel Institute, University of Minnesota, Austin, MN 55912, USA
    Cancer Res 68:2538-47. 2008
    ..Thus, MSK1 is required for tumor promoter-induced cell transformation through its phosphorylation of histone H3 at Ser(10) and AP-1 activation...
  99. ncbi Total synthesis of the N,C-coupled naphthylisoquinoline alkaloids ancistrocladinium A and B and related analogues
    Gerhard Bringmann
    Institute of Organic Chemistry, University of Wurzburg, Am Hubland, D 97074 Wurzburg, Germany
    J Am Chem Soc 132:1151-8. 2010
    ..Its general applicability was shown by the preparation of the sterically even more congested, as yet unnatural N,3'- and N,1'-coupled analogues, ancistrocladinium C (5) and D (6)...
  100. ncbi Syntheses and antitumor targeting G1 phase of the cell cycle of benzoyldihydroisoquinolines and related 1-substituted isoquinolines
    Almudena Bermejo
    Departamento de Farmacologia, Laboratorio de Farmacognosia, Universidad de Valencia, 46100 Burjassot, Spain
    J Med Chem 45:5058-68. 2002
    ..iii) Regarding the influence of the benzoylic moiety, both the unsubstituted (13, 8, 9, 11, 1, and 6) and the 3'-monosubstituted (22, 21, 20, and 19) compounds were more potent than compounds with other substitutions...
  101. ncbi Two activated stages of microglia and PET imaging of peripheral benzodiazepine receptors with [(11)C]PK11195 in rats
    Fumitaka Ito
    Department of Radiology, Fujita Health University, Kutsukake, Toyoake, Aichi, Japan
    Ann Nucl Med 24:163-9. 2010
    ..We evaluated whether [(11)C]PK11195 PET can indicate differences of microglial activation between no treatment and lipopolysaccharide (LPS) treatment in a rat artificial injury model of brain inflammation...

Research Grants65

  1. Synthesis of Medicinally Important Heterocycles
    RICHARD LAROCK; Fiscal Year: 2007
    ..affords very high yields of a wide variety of halogen-, sulfur- and selenium-substituted benzothiophenes, isoquinolines, benzofurans, and isocoumarins under exceptionally mild reaction conditions...
  2. Pilot-Scale Heterocyclic and Carbocyclic Libraries for High Throughout Screening
    RICHARD LAROCK; Fiscal Year: 2009
    ..coumarins, isocoumarins, phthalides, pyrones, 2-quinolones, pyridines, isoquinolin-1-ones, isoindolin-1-ones, isoquinolines, carbolines, isoindolo[2,1-a]indoles, carbazoles, dibenzofurans and various other heterocycles, plus indenones,..
  3. BENZODIAZEPINE DERIVED CARBORANES FOR N CAPTURE THERAPY
    JOHN NEUMEYER; Fiscal Year: 1992
    ..The initial objective of the Phase I effort will be the synthesis of several boron-containing isoquinolines structurally related to PK 11195 and their evaluation against malignant glioma cells, U251 human glioblastoma...
  4. MITOCHONDRIA, PESTICIDES, ISOQUINOLINES AND PARKINSON'S
    Howard Strahlendorf; Fiscal Year: 2001
    ..or by increasing the vulnerability of these neurons to selective detrimental effects of naturally occurring isoquinolines (IsoQ), specifically 1,2,3,4, tetrahydroisoquinoline (TIQ) and salsolinol (SAL)...
  5. Topoisomerase I-directed Anticancer Drugs
    Leroy Liu; Fiscal Year: 2004
    ..g. indolocarbazoles, nitidines, saintopin, morpholinyl doxorubicin, aclacinomycin A, indeno[1,2-c]isoquinolines, nogalamycin, actinomycin D, protoberberines, dibenzo[c,h]cinnolines, 2-phenylbenzimidazoles and ..
  6. ANTHRACYCLINES FROM ISOQUINOLINES
    RICHARD FRANCK; Fiscal Year: 1992
    ..The biological activity of the C-glycosides will provide important information about the requirements for cytotoxicity and cardiotoxicity of the parent compounds...
  7. Enabling Technologies for Combinatorial Chemistry
    K Nicolaou; Fiscal Year: 2005
    ..abstract_text> ..
  8. Morphine/NMDA interactions: Antinociceptive and discriminative stimulus effects
    BRADFORD FISCHER; Fiscal Year: 2007
    ..Findings from these experiments may have important clinical implications, and may lead to new pharmacotherapeutic strategies in the treatment of pain and drug abuse. [unreadable] [unreadable] [unreadable]..
  9. Imaging of Serotonin Transporters in Depression
    RAMIN PARSEY; Fiscal Year: 2005
    ..These goals will be met by a combination of didactic I course work and supervision. ..
  10. 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. ..
  11. Biological Predictors of Response to Antidepressants
    Ramin V Parsey; Fiscal Year: 2010
    ..Our overall goal is to reduce the trial and error associated with finding an effective antidepressant by using data from pre-treatment quantification of 5-HT1A receptors and 5-HTT to guide antidepressant treatment selection. ..
  12. Escalating Cocaine Self-Administration: NMDA Mechanisms
    Richard Allen; Fiscal Year: 2003
    ..abstract_text> ..
  13. Molecular Target Focused Discovery of Anticancer Drugs
    George R Pettit; Fiscal Year: 2010
    ....
  14. SYNTHESIS OF ANTICANCER AGENTS
    K C Nicolaou; Fiscal Year: 2010
    ..abstract_text> ..
  15. TOTAL SYNTHESIS OF NATURAL PRODUCTS
    K Nicolaou; Fiscal Year: 2002
    ..3] sigmatropic rearrangement and a radical based ring closure to form the bicyclic skeleton. ..
  16. DESIGN OF INHIBITORS OF EPINEPHRINE BIOSYNTHESIS
    GARY GRUNEWALD; Fiscal Year: 2005
    ..These inhibitors will be the first pharmacological tools available to help determine the function(s) of Epi in the CNS. This project is ripe and ready to burst forth with important new results. ..
  17. Molecular Target Focused Discovery of Anticancer Drugs
    GEORGE PETTIT; Fiscal Year: 2007
    ..In summary, the proposed research will be sharply aimed at the discovery and very rapid development of new anticancer drugs for the NCI programs direct at improving human cancer treatments. ..
  18. 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. ..
  19. 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. ..
  20. Alkynyliodonium Salts and Derived Diyls in Synthesis
    Ken Feldman; Fiscal Year: 2009
    ..abstract_text> ..
  21. COCAINE: A STUDY OF THE BIOCHEMICAL MECHANISM OF ACTION
    Frank Carroll; Fiscal Year: 2007
    ..abstract_text> ..
  22. Screen for Mycobacterium Tuberculosis (RMI)
    E White; Fiscal Year: 2005
    ..tuberculosis. 3) To study the effect of these novel inhibitors on the pantothenate pathway in M. smegmatis. 4) To co-crystallize these compounds with pantothenate synthetase to study their mode of binding ..
  23. PET Imaging MDMA Neurotoxicity
    Una McCann; Fiscal Year: 2006
    ..g., dementia, Parkinsonism, depression/anxiety). In addition, the proposed 18FDG studies will address the question of if MDMA exposure leads to altered brain function at the most fundamental level, glucose utilization. ..
  24. METHODOLOGY FOR THE SYNTHESIS OF NITROGEN HETEROCYCLES
    Philip Magnus; Fiscal Year: 2007
    ..The synthetic intermediates, particularly as they more closely resemble the natural products, will be screened to assess biological activity. [unreadable] [unreadable]..
  25. NOVEL PHARMACOTHERAPY FOR TREATMENT OF COCAINE ADDICTION
    Frank Carroll; Fiscal Year: 2008
    ..abstract_text> ..
  26. Design and Development of Pharmacotherapies for Treating Stimulant Abuse
    Frank Ivy Carroll; Fiscal Year: 2010
    ..3) To continue on a limited basis our development of selected 3-phenyltropane analogs as second-generation pharmacotherapies to treat cocaine addiction. ..
  27. Northeast Under/Grad Research Organization for Neuroscience
    Cheryl Frye; Fiscal Year: 2008
    ..Both of these outcomes are congruous with the Public Health Service's mission to ensure that there is a resource of well-trained scientists and health-care providers in the United States. [unreadable] [unreadable] [unreadable]..
  28. SYNTHESIS OF ANTIBIOTICS
    Andrew G Myers; Fiscal Year: 2010
    ..In addition, we will undertake basic studies to explore the feasibility of a novel macropolycyclization route to produce the new class of antibiotics known as the pyrrocidines. ..
  29. 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. ..
  30. NOVEL PHARMACOTHERAPIES FOR COCAINE DEPENDENCE
    Frank Carroll; Fiscal Year: 2001
    ..An ideal candidate compound would not only have efficacy in the preclinical models but would be safe, orally active, and potent, would not show tolerance or sensitization, and if abusable, would be less so than cocaine. ..
  31. SYNTHESIS OF DIAZONAMIDES
    Philip Magnus; Fiscal Year: 2004
    ..Part of the synthetic studies will involve the generation of persistent radical intermediates that should add to pi-deficient heterocycles and form the key central hindered bond present in the diazonamides. ..
  32. Novel antioxidant catalyst for transplant rejection
    Prakash Jagtap; Fiscal Year: 2003
    ..Phase II funding would support pharamcokinetic, toxicology, and pharmacodynamic studies required for IND submission and FDA-sanctioned clinical Phase I trials. ..
  33. Novel PARS inhibitor for therapy of colitis
    Prakash Jagtap; Fiscal Year: 2002
    ..These studies will provide the foundation for clinical testing, commercial development, and first market entry of an ultrapotent PARS inhibitor for therapy of IBD. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE ..
  34. PARS inhibitor for cardiac allotransplantation
    Prakash Jagtap; Fiscal Year: 2002
    ..Global markets are estimated at $400 million. Current market entrants such as cyclosporine A and FK506, have substantial toxicity. Funding of SBIR Phases I and II would allow for market entry in 4 years. ..
  35. Gene expression associated with the CNS reinforcing act*
    ZACHARY RODD HENRICKS; Fiscal Year: 2003
    ..The results of the proposed project will provide valuable information on neuronal systems and receptors within the extended amygdala involved in mediating the rewarding properties of alcohol. ..
  36. Sleep and Nocturnal Endocrine Function in MDMA User
    Una McCann; Fiscal Year: 2007
    ..Results from the proposed studies will help better define the functional consequences of MDMA exposure in humans, and could shed light on the roles of 5-HT and DA in sleep and nocturnal endocrine function. ..
  37. A Method To Study Membrane Protein Structure
    Guido Zampighi; Fiscal Year: 2003
    ....
  38. TRPV1 Expressing Sensory Afferents in Postoperative Pain
    Timothy Brennan; Fiscal Year: 2009
    ..A separate pathway, likely an A-fiber mediated pathway, is sufficient to transmit the enhanced mechanical responses. ..
  39. GAP JUNCTIONAL COMMUNICATIONS IN WOUND HEALING
    H Ehrlich; Fiscal Year: 2009
    ..abstract_text> ..
  40. NITROGEN HETEROCYCLES: METABOLIC EFFECTS AND TOXICITY
    Raymond F Novak; Fiscal Year: 2010
    ....
  41. Inflammation in obesity: Modulation by Weight Loss
    Paresh Dandona; Fiscal Year: 2009
    ..abstract_text> ..
  42. VASOMOTOR CONTROL OF DESCENDING VASA RECTA
    THOMAS PALLONE; Fiscal Year: 2003
    ....
  43. ROLE OF IMMUNE RESPONSIVENESS AND HIV ENCEPHALOPATHY
    Clayton Wiley; Fiscal Year: 2001
    ..These data will help design means of identifying subjects at risk for the development of CNS disease and help design therapies for arresting HIV encephalitis. ..
  44. MDMA Neurotoxicity in Nonhuman Primates
    George Ricaurte; Fiscal Year: 2005
    ..abstract_text> ..
  45. TEMPLATE POLYMERIZATION
    KENNETH SHEA; Fiscal Year: 2002
    ..This latter application will utilize a fluorescent signal to report the binding event. Finally we have proposed a study designed to get at how binding sites are created during the polymerization process. ..
  46. Mechanisms of HIV-Induced PNS Disease: The SIV Macaque Model
    Joseph Mankowski; Fiscal Year: 2009
    ..The goal of these comprehensive, integrated studies of HIV sensory neuropathy in our novel SIV primate model is to advance the understanding of HIV-SN pathogenesis to foster new therapeutic approaches. ..
  47. Agilent 5973 GC/MS System
    GARY MOLANDER; Fiscal Year: 2002
    ..Our current lack of such instrumentation negatively affects the ability to carry out many of these studies. This critical capability, in the form of an instrument for everyday analysis, is urgently needed. ..
  48. Motor Systems Supporting Pavlovian Conditioning
    Terry Crow; Fiscal Year: 2008
    ..These studies will help to elucidate general principles underlying the organization of polysensory neural systems generating behavior and their modification by learning. ..
  49. MOLECULAR MECHANISMS OF SCHWANN CELL MYELINATION
    Bruce Trapp; Fiscal Year: 2008
    ....
  50. Xenobiotics and Breast Epithelial Cell-ECM Signaling
    Raymond Novak; Fiscal Year: 2005
    ..The results of this proposal will provide novel information regarding chemical-mediated effects in breast epithelial cells and seminal data on fundamental cellular changes in human proliferative breast disease. ..
  51. REGULATION OF THE STEROIDOGENIC ACUTE REGULATORY PROTEIN
    Barbara Clark; Fiscal Year: 2005
    ..This will ultimately lead to a better understanding of potential developmental or disease states that result from aberrant over- or under-expression of StAR in a cell-specific manner. ..
  52. Partner of Under-Represented Scientists United for Educ
    LINDA DYKSTRA; Fiscal Year: 2005
    ..The Graduate School and individual doctoral granting departments at UNC-Chapel Hill will provide matching funds to promote the success of the program. ..
  53. Botanicals from Central America for Menopause
    Gail Mahady; Fiscal Year: 2005
    ..Successful validation and standardization of traditional plant-based medicines used to treat menopause has great significance not only for the women of Central America but the rest of the world as well. ..
  54. 2004 TERATOLOGY SOCIETY MEETINGS: TRAVEL FOR STUDENTS
    Thomas Knudsen; Fiscal Year: 2004
    ..Funds to help support and encourage student-fellow attendance at the Teratology Society 2004 meeting will enhance the quality of the meeting and the experience of the student attendees. ..
  55. Overcoming Barriers to Early Phase Clinical Trials
    Bruce Chabner; Fiscal Year: 2004
    ....
  56. Red Blood Cell Adhesion in Sickle Cell Disease
    CHERYL HILLERY; Fiscal Year: 2005
    ..Thus, we expect that information derived from this proposal will lead to new therapeutic approaches for the treatment of vaso-occlusion in SS-D. ..
  57. ALVEOLAR TYPE II CELL GROWTH IN INJURY
    RANDOLPH HASTINGS; Fiscal Year: 2003
    ..The project will evaluate the potential use of PTHrP-related therapeutic interventions that might speed or improve recovery following silica-induced lung injury. ..
  58. Reactive Oxygen Species American Society of Nephrology Fall 2007
    THOMAS PALLONE; Fiscal Year: 2007
    ..Attendance of young scientists insures that the information will be translated into future studies that elucidate the role of ROS in kidney diseases and treatment thereof. [unreadable] [unreadable] [unreadable]..
  59. 2003 TERATOLOGY SOCIETY MEETINGS: TRAVEL FOR STUDENTS
    Thomas Knudsen; Fiscal Year: 2003
    ..Funds to help support and encourage student-fellow attendance at the Teratology Society 2003 meeting will enhance the quality of the meeting and the experience of the student attendees. ..
  60. Stem Cell-Seeded ECM Scaffolds for Neurotransplantation
    MICHELLE LAPLACA; Fiscal Year: 2004
    ..abstract_text> ..
  61. RETINOID REGULATION OF BLOOD VESSEL FORMATION
    Karen Hirschi; Fiscal Year: 2004
    ..We will also specifically investigate the role(s) of retinoic acid and TGF-¿ signaling in the control of endothelial cell maturation and growth, as a direct extension of our previous work. ..
  62. Cyclic AMP signaling in cardiac myocytes
    THOMAS RICH; Fiscal Year: 2007
    ..g., protenoid, beta1-,or beta2-adrenergic receptors) or inhibit phosphodiesterase (PDE) will shed new light on the physiologic functions of these enzymes and their relation to cardiac function. ..
  63. Antipsychotic Actions in Models of NMDA Hypofunction
    Gary Duncan; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  64. Development of cAMP Biosensor, High Content Imaging, and Functional GLP-1R aSSAYS
    Philip LoGrasso; Fiscal Year: 2010
    ....
  65. TRANSPORT BY OCULAR EPITHELIAL CELLS
    MORTIMER CIVAN; Fiscal Year: 2005
    ..abstract_text> ..