pyrrolidinones

Summary

Summary: A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)

Top Publications

  1. pmc Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy
    Steven A Yukl
    San Francisco VA Medical Center SFVAMC and University of California, San Francisco UCSF, San Francisco, California, USA
    AIDS 24:2451-60. 2010
  2. pmc HIV-1 integrase inhibitor resistance and its clinical implications
    Jose Luis Blanco
    Infectious Diseases Unit, University of Barcelona, Spain
    J Infect Dis 203:1204-14. 2011
  3. ncbi Raltegravir: the first HIV-1 integrase strand transfer inhibitor in the HIV armamentarium
    Bach Yen T Nguyen
    ISENTRESS Discovery and Development Team, Merck Research Laboratories, North Wales, Pennsylvania 19454 1099, USA
    Ann N Y Acad Sci 1222:83-9. 2011
  4. ncbi ARQ 197, a novel and selective inhibitor of the human c-Met receptor tyrosine kinase with antitumor activity
    Neru Munshi
    Boston Biomedical, Inc, Norwood, Massachusetts, USA
    Mol Cancer Ther 9:1544-53. 2010
  5. ncbi Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies
    Timothy A Yap
    Royal Marsden National Health Service Foundation Trust, The Institute of Cancer Research, Sutton, Surrey, UK
    J Clin Oncol 29:1271-9. 2011
  6. pmc Cross-resistance profile determination of two second-generation HIV-1 integrase inhibitors using a panel of recombinant viruses derived from raltegravir-treated clinical isolates
    L van Wesenbeeck
    Tibotec Virco, Beerse, Belgium
    Antimicrob Agents Chemother 55:321-5. 2011
  7. ncbi Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses
    Jeffrey L Lennox
    Emory University School of Medicine, Atlanta, GA, USA
    J Acquir Immune Defic Syndr 55:39-48. 2010
  8. pmc Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance
    Stephen Hare
    Division of Infectious Diseases, Imperial College London, London W2 1PG, United Kingdom
    Proc Natl Acad Sci U S A 107:20057-62. 2010
  9. pmc Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy
    D McMahon
    Department of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Clin Infect Dis 50:912-9. 2010
  10. pmc Study of genotypic and phenotypic HIV-1 dynamics of integrase mutations during raltegravir treatment: a refined analysis by ultra-deep 454 pyrosequencing
    Daniele Armenia
    University of Rome Tor Vergata, Rome, Italy
    J Infect Dis 205:557-67. 2012

Detail Information

Publications274 found, 100 shown here

  1. pmc Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy
    Steven A Yukl
    San Francisco VA Medical Center SFVAMC and University of California, San Francisco UCSF, San Francisco, California, USA
    AIDS 24:2451-60. 2010
    ..To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut...
  2. pmc HIV-1 integrase inhibitor resistance and its clinical implications
    Jose Luis Blanco
    Infectious Diseases Unit, University of Barcelona, Spain
    J Infect Dis 203:1204-14. 2011
    ..This perspective reviews the genetic mechanisms of INI resistance and their implications for initial INI therapy, the treatment of antiretroviral-experienced patients, and regimen simplification...
  3. ncbi Raltegravir: the first HIV-1 integrase strand transfer inhibitor in the HIV armamentarium
    Bach Yen T Nguyen
    ISENTRESS Discovery and Development Team, Merck Research Laboratories, North Wales, Pennsylvania 19454 1099, USA
    Ann N Y Acad Sci 1222:83-9. 2011
    ..Raltegravir represents an important addition to the current armamentarium for the treatment of HIV infection...
  4. ncbi ARQ 197, a novel and selective inhibitor of the human c-Met receptor tyrosine kinase with antitumor activity
    Neru Munshi
    Boston Biomedical, Inc, Norwood, Massachusetts, USA
    Mol Cancer Ther 9:1544-53. 2010
    ..Cumulatively, these data suggest that ARQ 197, currently in phase II clinical trials, is a promising agent for targeting cancers in which c-Met-driven signaling is important for their survival and proliferation...
  5. ncbi Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies
    Timothy A Yap
    Royal Marsden National Health Service Foundation Trust, The Institute of Cancer Research, Sutton, Surrey, UK
    J Clin Oncol 29:1271-9. 2011
    ..A phase I trial of ARQ 197 was conducted to assess safety, tolerability, and target inhibition, including intratumoral c-MET signaling, apoptosis, and angiogenesis...
  6. pmc Cross-resistance profile determination of two second-generation HIV-1 integrase inhibitors using a panel of recombinant viruses derived from raltegravir-treated clinical isolates
    L van Wesenbeeck
    Tibotec Virco, Beerse, Belgium
    Antimicrob Agents Chemother 55:321-5. 2011
    ..The order according to decreasing susceptibility is compound G, MK-2048, and EVG...
  7. ncbi Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses
    Jeffrey L Lennox
    Emory University School of Medicine, Atlanta, GA, USA
    J Acquir Immune Defic Syndr 55:39-48. 2010
    ..We analyzed the 96-week results in the overall population and in prespecified subgroups from the ongoing STARTMRK study of treatment-naive HIV-infected patients...
  8. pmc Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance
    Stephen Hare
    Division of Infectious Diseases, Imperial College London, London W2 1PG, United Kingdom
    Proc Natl Acad Sci U S A 107:20057-62. 2010
    ..Furthermore, our structures predict physical proximity and an interaction between HIV-1 IN mutant residues His148 and Ser/Ala140, rationalizing the coevolution of Q148H and G140S/A mutations in drug-resistant viral strains...
  9. pmc Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy
    D McMahon
    Department of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Clin Infect Dis 50:912-9. 2010
    ..We investigated whether intensification with the integrase inhibitor raltegravir decreases plasma HIV-1 RNA levels in patients receiving suppressive antiretroviral therapy...
  10. pmc Study of genotypic and phenotypic HIV-1 dynamics of integrase mutations during raltegravir treatment: a refined analysis by ultra-deep 454 pyrosequencing
    Daniele Armenia
    University of Rome Tor Vergata, Rome, Italy
    J Infect Dis 205:557-67. 2012
    ..The dynamics of raltegravir-resistant variants and their impact on virologic response in 23 HIV-1-infected patients, who started a salvage raltegravir-containing regimen, were investigated...
  11. ncbi Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection
    Vincenzo Summa
    Istituto di Ricerche di Biologia Molecolare, P Angeletti SpA Merck Research Laboratories, Rome, Via Pontina Km 30, 600, 00040 Pomezia, Italy
    J Med Chem 51:5843-55. 2008
    ....
  12. pmc Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262)
    Babafemi Taiwo
    Division of Infectious Diseases, Northwestern University, Chicago, Illinois 60611, USA
    AIDS 25:2113-22. 2011
    ..To explore darunavir/ritonavir (DRV/r) plus raltegravir (RAL) combination therapy in antiretroviral-naive patients...
  13. ncbi Examination of noninferiority, safety, and tolerability of lopinavir/ritonavir and raltegravir compared with lopinavir/ritonavir and tenofovir/ emtricitabine in antiretroviral-naïve subjects: the progress study, 48-week results
    Jacques Reynes
    Department of Infectious and Tropical Diseases, Montpellier University Hospital, Montpellier, France
    HIV Clin Trials 12:255-67. 2011
    ..The purpose of this study is to evaluate whether a new NRTI-sparing regimen may provide an alternative for persons for whom traditional regimens may not be the best option...
  14. ncbi Body composition changes after switching from protease inhibitors to raltegravir: SPIRAL-LIP substudy
    Adrian Curran
    Hospital Universitari Vall d Hebron, Universitat Autonoma de Barcelona, Infectious Diseases Department, Spain
    AIDS 26:475-81. 2012
    ..To compare 48-week changes in body fat distribution and bone mineral density (BMD) between patients switching from a ritonavir-boosted protease inhibitor (PI/r) to raltegravir (RAL) and patients continuing with PI/r...
  15. ncbi A phase I dose-escalation study of Tivantinib (ARQ 197) in adult patients with metastatic solid tumors
    Lee S Rosen
    UCLA Division of Hematology Oncology, Los Angeles, CA 90404, USA
    Clin Cancer Res 17:7754-64. 2011
    ..This open-label, phase I, dose-escalation study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of tivantinib in patients with advanced or metastatic solid tumors refractory to standard therapy...
  16. pmc Revisiting quorum sensing: Discovery of additional chemical and biological functions for 3-oxo-N-acylhomoserine lactones
    Gunnar F Kaufmann
    Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 102:309-14. 2005
    ..These findings merit new attention such that other previously identified autoinducers be reevaluated for additional biological functions...
  17. ncbi Identification of a hybrid PKS/NRPS required for pseurotin A biosynthesis in the human pathogen Aspergillus fumigatus
    Shubha Maiya
    University of Sheffield, Department of Molecular Biology and Biotechnology, S10 2TN, Sheffield, UK
    Chembiochem 8:1736-43. 2007
    ..It is likely that the first product of psoA is converted to pseurotin A by the products of other genes in this cluster...
  18. pmc Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo
    Olivier Delelis
    LBPA, CNRS UMR8113, Ecole Normale Superieure de Cachan, 61 Avenue du President Wilson, 94235 Cachan, France
    Antimicrob Agents Chemother 54:491-501. 2010
    ..Altogether our results not only show that the mutation at position Y143 is one of the mechanisms conferring resistance to RAL but also explain the delayed emergence of this mutation...
  19. pmc Raltegravir cerebrospinal fluid concentrations in HIV-1 infection
    Aylin Yilmaz
    Department of Infectious Diseases, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
    PLoS ONE 4:e6877. 2009
    ..In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF) and plasma in subjects receiving antiretroviral treatment regimens containing this drug...
  20. ncbi Strand transfer inhibitors of HIV-1 integrase: bringing IN a new era of antiretroviral therapy
    Damian J McColl
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, United States
    Antiviral Res 85:101-18. 2010
    ..This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010...
  21. ncbi Abrogation of heat shock protein 70 induction as a strategy to increase antileukemia activity of heat shock protein 90 inhibitor 17-allylamino-demethoxy geldanamycin
    Fei Guo
    Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida 33612, USA
    Cancer Res 65:10536-44. 2005
    ..Collectively, these data indicate that induction of hsp70 attenuates the apoptotic effects of 17-AAG, and abrogation of hsp70 induction significantly enhances the antileukemia activity of 17-AAG...
  22. ncbi Potential of novel antiretrovirals to modulate expression and function of drug transporters in vitro
    Nadine Cécile Luise Zembruski
    Department of Clinical Pharmacology and Pharmacoepidemiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
    J Antimicrob Chemother 66:802-12. 2011
    ..To expand knowledge on drug-drug interactions of these antiretrovirals we investigated whether these compounds are substrates, inhibitors or inducers of important ABC transporters...
  23. pmc Early clinical development of ARQ 197, a selective, non-ATP-competitive inhibitor targeting MET tyrosine kinase for the treatment of advanced cancers
    Alex A Adjei
    Roswell Park Cancer Institute, Buffalo, New York, USA
    Oncologist 16:788-99. 2011
    ....
  24. ncbi A genotypic assay for the amplification and sequencing of integrase from diverse HIV-1 group M subtypes
    Kristel Van Laethem
    Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium
    J Virol Methods 153:176-81. 2008
    ..The relevance of these polymorphisms in the absence of the signature mutations remains unclear...
  25. pmc Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers
    J Hirvonen
    Molecular Imaging Branch, National Institute of Mental Health, NIH, Bethesda, MD 20892 1026, USA
    Mol Psychiatry 17:642-9. 2012
    ..This is the first direct demonstration of cortical cannabinoid CB(1) receptor downregulation as a neuroadaptation that may promote cannabis dependence in human brain...
  26. pmc No effect of raltegravir intensification on viral replication markers in the blood of HIV-1-infected patients receiving antiretroviral therapy
    Rajesh T Gandhi
    Division of Infectious Diseases and Ragon Institute, Massachusetts General Hospital, Boston, MA 02114, USA
    J Acquir Immune Defic Syndr 59:229-35. 2012
    ..Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1 replication...
  27. pmc Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir
    Danielle Perez Bercoff
    Laboratoire de Retrovirologie, CRP Sante, Luxembourg, Luxembourg
    Retrovirology 7:98. 2010
    ..Regimens including integrase inhibitors (INI) seem to be effective, but little data on HIV-2 integrase (IN) polymorphisms and resistance pathways are available...
  28. ncbi Receptor-induced transient reduction in plasma membrane PtdIns(4,5)P2 concentration monitored in living cells
    T P Stauffer
    Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    Curr Biol 8:343-6. 1998
    ..Overall, our studies show that PtdIns(4,5)P2 can have second messenger functions of its own, by mediating a transient dissociation of proteins anchored in the plasma membrane...
  29. pmc Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes
    D A Matthews
    Agouron Pharmaceuticals, Inc, 3565 General Atomics Court, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 96:11000-7. 1999
    ..Recently, one compound in this series, AG7088, has entered clinical trials...
  30. ncbi HIV-1 resistance patterns to integrase inhibitors in antiretroviral-experienced patients with virological failure on raltegravir-containing regimens
    Daniel Da Silva
    Laboratoire de Virologie, Bordeaux University Hospital, and EA2968, Universite Victor Segalen, Bordeaux, France
    J Antimicrob Chemother 65:1262-9. 2010
    ..Our aim was to study the in vivo viral genetic pathways for resistance to raltegravir, in antiretroviral-experienced patients with virological failure (VF) on raltegravir-containing regimens...
  31. ncbi Evolution of raltegravir resistance during therapy
    Nadine Sichtig
    Institute of Virology, University of Cologne, Germany
    J Antimicrob Chemother 64:25-32. 2009
    ..We investigated the prevalence of raltegravir resistance-associated mutations at baseline and their evolution during raltegravir therapy in patients infected with different HIV-1 subtypes...
  32. ncbi Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles
    Olivia Goethals
    Tibotec Virco Virology BVBA, Gen De Wittelaan L 11B 3, 2800 Mechelen, Belgium
    Virology 402:338-46. 2010
    ..These data improve the understanding of resistance against raltegravir and cross-resistance to MK-2048 and other integrase inhibitors, which will aid in the discovery of second-generation integrase inhibitors...
  33. ncbi Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol
    T Hofmann
    Institut fur Pharmakologie, Universitatsklinikum Benjamin Franklin, Freie Universitat Berlin, Germany
    Nature 397:259-63. 1999
    ..Thus, hTRPC3 and hTRPC6 represent the first members of a new functional family of second-messenger-operated cation channels, which are activated by diacylglycerol...
  34. ncbi Roles of Pseudomonas aeruginosa autoinducers and their degradation products, tetramic acids, in bacterial survival and behavior in ecological niches
    Natsue Hosono Honda
    Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo 143 8530, Japan
    Microbes Environ 26:160-4. 2011
    ..Tetramic acid and disinfectants acted synergistically to kill P. aeruginosa. These results suggest the AHL-degradation product tetramic acid to be useful for bacterial control...
  35. pmc Raltegravir is a substrate for SLC22A6: a putative mechanism for the interaction between raltegravir and tenofovir
    Darren M Moss
    Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom
    Antimicrob Agents Chemother 55:879-87. 2011
    ..However, transport was limited compared to endogenous controls, and these transporters are unlikely to have a great impact on raltegravir pharmacokinetics...
  36. ncbi Simplification from protease inhibitors to once- or twice-daily raltegravir: the ODIS trial
    Eugenia Vispo
    Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain
    HIV Clin Trials 11:197-204. 2010
    ..Raltegravir has demonstrated good antiviral activity and safety profile in twice-daily (bid) dosing. However, its long terminal elimination half-life might allow once-daily (qd) administration...
  37. ncbi Tetramic and tetronic acids: an update on new derivatives and biological aspects
    Rainer Schobert
    Organic Chemistry Laboratory, University of Bayreuth, Bayreuth, Germany
    Bioorg Med Chem 16:4203-21. 2008
    ..Important new members of the title compound families isolated since the year 2000 are covered as well as new biological aspects of some earlier congeners...
  38. pmc A switch in therapy to a reverse transcriptase inhibitor sparing combination of lopinavir/ritonavir and raltegravir in virologically suppressed HIV-infected patients: a pilot randomized trial to assess efficacy and safety profile: the KITE study
    Ighovwerha Ofotokun
    Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, Georgia 30303, USA
    AIDS Res Hum Retroviruses 28:1196-206. 2012
    ..AEs were comparable between arms, but the LPV-r/RAL arm experienced higher triglyceridemia...
  39. pmc Defining the mode of action of tetramic acid antibacterials derived from Pseudomonas aeruginosa quorum sensing signals
    Colin A Lowery
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 131:14473-9. 2009
    ....
  40. ncbi In vitro resistance selections using elvitegravir, raltegravir, and two metabolites of elvitegravir M1 and M4
    Nicolas A Margot
    Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA 94404, USA
    Antiviral Res 93:288-96. 2012
    ....
  41. pmc Substitutions at amino acid positions 143, 148, and 155 of HIV-1 integrase define distinct genetic barriers to raltegravir resistance in vivo
    Signe Fransen
    Monogram Biosciences, South San Francisco, California, USA
    J Virol 86:7249-55. 2012
    ..These selective pressures result in the displacement of N155H variants by 143 or 148 variants under continued drug exposure...
  42. ncbi Ionotropic glutamate receptor (iGluR)-like channels mediate MAMP-induced calcium influx in Arabidopsis thaliana
    Mark Kwaaitaal
    Max Planck Institute for Plant Breeding Research, Department of Plant Microbe Interactions, Carl von Linne Weg 10, 50829 Köln, Germany
    Biochem J 440:355-65. 2011
    ..We conclude that the initiation of innate immune responses upon flg22, elf18 and chitin recognition involves apoplastic Ca2+ influx via iGluR-like channels...
  43. ncbi Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir
    Filippo Canducci
    Vita Salute San Raffaele University, Laboratory of Virology and Microbiology, Milan, Italy
    J Infect Dis 204:1811-5. 2011
    ..However, viruses with mutation Q148R associated with secondary mutations and the combination Q148H+G140S were instead associated with a reduced level of susceptibility to dolutegravir in vitro...
  44. pmc Comprehensive characterization of heat shock protein 27 phosphorylation in human endothelial cells stimulated by the microbial dithiole thiolutin
    Shujia Dai
    Barnett Institute, Northeastern University, Boston, Massachusetts 02115, USA
    J Proteome Res 7:4384-95. 2008
    ....
  45. pmc Deep molecular characterization of HIV-1 dynamics under suppressive HAART
    Maria J Buzon
    Institut de Recerca de la SIDA, IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain
    PLoS Pathog 7:e1002314. 2011
    ....
  46. pmc Quantitative prediction of integrase inhibitor resistance from genotype through consensus linear regression modeling
    Koen Van Der Borght
    Tibotec Virco, Beerse, Belgium
    Virol J 10:8. 2013
    ..We developed a linear regression modeling approach to make a quantitative raltegravir (RAL) resistance phenotype prediction, as Fold Change in IC50 against a wild type virus, from mutations in the integrase genotype...
  47. ncbi Determination of P-glycoprotein surface expression and functional ability after in vitro treatment with darunavir or raltegravir in lymphocytes of healthy donors
    Massimo Tempestilli
    National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Via Portuense 292, 00149 Rome, Italy
    Int Immunopharmacol 16:492-7. 2013
    ..Our study highlights the need for studies on drug interactions via the P-gp modulation mechanism, especially with the current multi-drug regimens...
  48. ncbi Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial
    Jeffrey L Lennox
    Emory University School of Medicine, Atlanta, GA, USA
    Lancet 374:796-806. 2009
    ..We compared the safety and efficacy of raltegravir with efavirenz as part of combination antiretroviral therapy for treatment-naive patients...
  49. ncbi Natural polymorphisms of integrase among HIV type 1-infected South African patients
    Muhammad Q Fish
    HIV Pathogenesis Research Laboratory, Department of Molecular Medicine and Haematology, University of Witwatersrand Medical School, Parktown, Johannesburg, South Africa
    AIDS Res Hum Retroviruses 26:489-93. 2010
    ..However, the impact of E157Q and other naturally occurring polymorphisms warrants further phenotypic investigation...
  50. pmc Response of a simian immunodeficiency virus (SIVmac251) to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy
    Mark G Lewis
    Department of Infectious, Parasitic and Immune Mediated Diseases, Istituto Superiore di Sanita, Viale Regina Elena, 299, 00161, Rome, Italy
    Retrovirology 7:21. 2010
    ....
  51. ncbi Dynamic escape of pre-existing raltegravir-resistant HIV-1 from raltegravir selection pressure
    Francisco M Codoñer
    HIVACAT, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
    Antiviral Res 88:281-6. 2010
    ....
  52. pmc Transmitted raltegravir resistance in an HIV-1 CRF_AG-infected patient
    Sarita D Boyd
    SAIC Frederick, Inc, MD, USA
    Antivir Ther 16:257-61. 2011
    ..We suggest obtaining a pretreatment integrase genotype in patients with transmitted multiclass drug resistance in order to create an optimal first regimen and increase the chance for virological suppression...
  53. pmc MK-0536 inhibits HIV-1 integrases resistant to raltegravir
    Mathieu Metifiot
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, Maryland 20892, USA
    Antimicrob Agents Chemother 55:5127-33. 2011
    ..Modeling of IN developed from recent prototype foamy virus structures is presented to account for the differences in the drug activities of MK-0536 and RAL against the IN mutants...
  54. pmc G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not
    Xiao Ju Ni
    LBPA, CNRS, Ecole Normale Superieure de Cachan, Cachan, France
    Retrovirology 8:68. 2011
    ..The resistance of HIV-1 IN has been confirmed in vitro for mutated enzymes harboring these mutations, but no such confirmation has yet been obtained for HIV-2...
  55. ncbi The dynamics of appearance and disappearance of HIV-1 integrase mutations during and after withdrawal of raltegravir therapy
    Ruth Bridget Ferns
    Division of Infection and Immunity, University College London, London, UK
    AIDS 23:2159-64. 2009
    ..To monitor HIV-1 integrase resistance mutations during raltegravir (RAL) therapy, including the impact of RAL interruption...
  56. ncbi Clinical efficacy of raltegravir against B and non-B subtype HIV-1 in phase III clinical studies
    Jurgen K Rockstroh
    University of Bonn, Bonn Venusberg, Germany
    AIDS 25:1365-9. 2011
    ..We evaluated the long-term efficacy of raltegravir according to HIV-1 subtype (B and non-B) using data from three phase III studies in treatment-experienced (BENCHMRK-1 and 2) and treatment-naive (STARTMRK) HIV-infected patients...
  57. ncbi Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: a randomized 48-week study
    Josep M Llibre
    Lluita contra la SIDA Foundation, Hospital Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain
    Antivir Ther 17:355-64. 2012
    ..The intensification with raltegravir could impact latent reservoirs and might lead to a reduction of plasma HIV-1 viraemia (viral load [VL]), complementary DNA intermediates and immune activation...
  58. ncbi Transmission of integrase strand-transfer inhibitor multidrug-resistant HIV-1: case report and response to raltegravir-containing antiretroviral therapy
    Benjamin Young
    Rocky Mountain CARES DIDC, Denver, CO, USA
    Antivir Ther 16:253-6. 2011
    ..This case illustrates an emerging need to consider the possibility of acquired INI resistance among newly diagnosed treatment-naive individuals harbouring multidrug-resistant HIV-1...
  59. pmc Biochemical and pharmacological analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir
    Mathieu Metifiot
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Bethesda, Maryland 20892, USA
    Biochemistry 49:3715-22. 2010
    ..Our results demonstrate that IN mutations at positions 140 and 148 in the IN flexible loop can account for the phenotype of RAL-resistant viruses...
  60. ncbi Switch from enfuvirtide to raltegravir in virologically suppressed multidrug-resistant HIV-1-infected patients: a randomized open-label trial
    Nathalie de Castro
    Department of Infectious Diseases, Assistance Publique Hopitaux de Paris, Saint Louis Hospital and University of Paris VII Denis Diderot, Paris, France
    Clin Infect Dis 49:1259-67. 2009
    ..We conducted a prospective, randomized, open-label trial to compare the antiviral efficacy and safety of a switch to raltegravir with the efficacy and safety of continuing enfuvirtide...
  61. ncbi Long-term efficacy and safety of the HIV integrase inhibitor raltegravir in patients with limited treatment options in a Phase II study
    Jose M Gatell
    University of Barcelona, Barcelona, Spain
    J Acquir Immune Defic Syndr 53:456-63. 2010
    ..Raltegravir in combination therapy has demonstrated potent suppression of HIV-1 with a favorable safety profile. This report provides 96-week efficacy and safety data from Protocol 005, a Phase II study...
  62. pmc Longitudinal analysis of raltegravir susceptibility and integrase replication capacity of human immunodeficiency virus type 1 during virologic failure
    Signe Fransen
    Monogram Biosciences, South San Francisco, California, USA
    Antimicrob Agents Chemother 53:4522-4. 2009
    ....
  63. ncbi Extracellular calcium-sensing receptor mediated signalling is involved in human vascular smooth muscle cell proliferation and apoptosis
    Guerman Molostvov
    The Clinical Sciences Research Institute, Warwick Medical School, Coventry, UK
    Cell Physiol Biochem 22:413-22. 2008
    ..05). In conclusion, stimulation of CaSR leads to activation of MEK1/ERK1,2 and PLC pathways and up-regulation of cell proliferation. CaSR-mediated PLC activation is important for SMC survival and protection against apoptosis...
  64. pmc Hot spots of integrase genotypic changes leading to HIV-2 resistance to raltegravir
    Charlotte Charpentier
    Hopital Bichat Claude Bernard, Laboratoire de Virologie, 46 rue Henri Huchard, 75018 Paris, France
    Antimicrob Agents Chemother 55:1293-5. 2011
    ..Thus, despite a 40% difference in integrase genes between HIV-1 and HIV-2, the genetic pathways leading to raltegravir resistance are similar...
  65. ncbi Mutation N155H in HIV-2 integrase confers high phenotypic resistance to raltegravir and impairs replication capacity
    Maria Salgado
    Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain
    J Clin Virol 46:173-5. 2009
    ..Due to the recent introduction of these novel inhibitors, information on the selection of resistance mutations and its phenotypic effect in this population is scarce...
  66. ncbi Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimens
    Fausto Baldanti
    Virology Unit, Foundation IRCCS Policlinico San Matteo, Pavia, Italy
    J Med Virol 82:116-22. 2010
    ..The effect of single and multiple mutations on integrase activity, raltegravir susceptibility, and on the capacity of viral replication remains to be elucidated...
  67. pmc Secondary integrase resistance mutations found in HIV-1 minority quasispecies in integrase therapy-naive patients have little or no effect on susceptibility to integrase inhibitors
    Francesca Ceccherini-Silberstein
    Department of Experimental Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
    Antimicrob Agents Chemother 54:3938-48. 2010
    ....
  68. ncbi Elvitegravir overcomes resistance to raltegravir induced by integrase mutation Y143
    Mathieu Metifiot
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    AIDS 25:1175-8. 2011
    ..In this study, we characterized elvitegravir activity in the context of raltegravir resistance mutations...
  69. ncbi Dynamic patterns of human immunodeficiency virus type 1 integrase gene evolution in patients failing raltegravir-based salvage therapies
    Filippo Canducci
    Universita Vita Salute San Raffaele, Italy
    AIDS 23:455-60. 2009
    ..Evaluate HIV-1 subtype B integrase gene evolution in patients failing raltegravir (RAL)-based savage regimens by clonal analysis of the replicating viral quasispecies...
  70. pmc Molecular dynamics approaches estimate the binding energy of HIV-1 integrase inhibitors and correlate with in vitro activity
    Barry C Johnson
    HIV Drug Resistance Program, National Cancer Institute Frederick, National Institutes of Health, Frederick, Maryland, USA
    Antimicrob Agents Chemother 56:411-9. 2012
    ....
  71. ncbi ARQ-197, an oral small-molecule inhibitor of c-Met for the treatment of solid tumors
    Rakesh Bagai
    Case Western Reserve University, Ireland Cancer Center, University Hospitals Case Medical Center, Division of Hematology Oncology, Department of Medicine, 10900 Euclid Avenue, WRB 2 123, Cleveland, OH 44106, USA
    IDrugs 13:404-14. 2010
    ....
  72. ncbi Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study
    Martin Markowitz
    Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY, USA
    J Acquir Immune Defic Syndr 46:125-33. 2007
    ..This study explored the antiretroviral activity and safety of raltegravir in treatment-naive patients with plasma HIV-1 RNA levels > or = 5000 copies/mL and CD4 T-cell counts > or = 100 cells/mm...
  73. ncbi Raltegravir and unboosted atazanavir dual therapy in virologically suppressed antiretroviral treatment-experienced HIV patients
    Damien V Cordery
    National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia
    Antivir Ther 15:1035-8. 2010
    ....
  74. ncbi Pseurotin A and its analogues as inhibitors of immunoglobulin E [correction of immunoglobuline E] production
    Minoru Ishikawa
    Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd, 760 Morooka cho, Kohoku Ku, Yokohama 222 8567, Japan
    Bioorg Med Chem Lett 19:1457-60. 2009
    ..066 microM. An immunosuppressive activity of another natural product, synerazol was also found...
  75. ncbi Phospholipase C isoforms are localized at the cleavage furrow during cytokinesis
    Yoko Naito
    Laboratory of Biological Signaling, Graduate School of Life Science, University of Hyogo, Harima Science Garden City, Hyogo 678 1297
    J Biochem 140:785-91. 2006
    ....
  76. ncbi Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials
    Roy T Steigbigel
    State University of New York at Stony Brook, The Rockefeller University, New York, New York, USA
    Clin Infect Dis 50:605-12. 2010
    ....
  77. pmc HIV-1 integrase sequence variability in antiretroviral naïve patients and in triple-class experienced patients subsequently treated with raltegravir
    Vici Varghese
    Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA
    AIDS Res Hum Retroviruses 26:1323-6. 2010
    ..However, none of the major INI-resistance mutations was found to be polymorphic in either study and there were no significant changes in the prevalence of any of the minor INI-resistance mutations...
  78. pmc Differential sensitivities of retroviruses to integrase strand transfer inhibitors
    Yasuhiro Koh
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, CLS 1010, Boston, MA 02115, USA
    J Virol 85:3677-82. 2011
    ..The drugs intermediately inhibited intracisternal A-particle retrotransposition but were inactive against Sleeping Beauty transposition and long interspersed nucleotide element 1 (LINE-1) retrotransposition...
  79. pmc Synthesis, ex vivo evaluation, and radiolabeling of potent 1,5-diphenylpyrrolidin-2-one cannabinoid subtype-1 receptor ligands as candidates for in vivo imaging
    Sean R Donohue
    Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Med Chem 51:5833-42. 2008
    ....
  80. ncbi Dynamics of raltegravir resistance profile in an HIV type 2-infected patient
    Li Xu
    Health Protection Agency, Heart of England NHS Foundation Trust, Birmingham B9 5SS, UK
    AIDS Res Hum Retroviruses 25:843-7. 2009
    ..Our findings provide evidence supporting the supposition that substantial cross-resistance between strand transfer IN-Is is likely in HIV-2 as shown in HIV-1...
  81. pmc Anti-Clostridium difficile potential of tetramic acid derivatives from Pseudomonas aeruginosa quorum-sensing autoinducers
    Chihiro Ueda
    Department of Microbiology and Infectious Diseases, Toho University School of Medicine, 5 21 16 Ohmorinishi, Ohtaku, Tokyo 143 8540, Japan
    Antimicrob Agents Chemother 54:683-8. 2010
    ..These results suggest the potential for tetramic acid derivatives to be novel agents with activity against C. difficile...
  82. ncbi Modulation of dopamine receptor agonist-induced rotational behavior in 6-OHDA-lesioned rats by a peptidomimetic analogue of Pro-Leu-Gly-NH2 (PLG)
    R K Mishra
    Department of Psychiatry, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
    Peptides 18:1209-15. 1997
    ..In summary, the results of this study indicate that PAOPA, a conformationally constrained peptidomimetic analogue of PLG, can modulate dopaminergic activity in vivo with higher potency and efficacy than PLG...
  83. ncbi Clinical pharmacology profile of raltegravir, an HIV-1 integrase strand transfer inhibitor
    Diana M Brainard
    Merck Sharp and Dohme Corp, Whitehouse Station, New Jersey, USA
    J Clin Pharmacol 51:1376-402. 2011
    ....
  84. ncbi Meldrum's acid and related compounds in the synthesis of natural products and analogs
    Andrey S Ivanov
    Pharm Sintez, 117312, Vavilova Str 15, Moscow, Russia
    Chem Soc Rev 37:789-811. 2008
    ..This critical review focuses on applications of Meldrum's acid and its derivatives to the synthesis of natural products and analogs. It covers all relevant literature from 1991 to August 2007 (181 references)...
  85. ncbi 4,5-Disubstituted cis-pyrrolidinones as inhibitors of type II 17beta-hydroxysteroid dehydrogenase. Part 3. Identification of lead candidate
    Jill Wood
    Bayer Research Center, Bayer HealthCare, Pharmaceutical Division, 400 Morgan Lane, West Haven, CT 06516, USA
    Bioorg Med Chem Lett 16:4965-8. 2006
    A series of 4,5-disubstituted cis-pyrrolidinones was investigated as inhibitors of 17beta-HSD II for the treatment of osteoporosis. Biochemical data for several compounds are given. Compound 42 was selected as the lead candidate.
  86. ncbi Prevalence of HIV-1 integrase mutations related to resistance to dolutegravir in raltegravir naïve and pretreated patients
    F Saladini
    Department of Biotechnology, University of Siena, Siena, Italy
    Clin Microbiol Infect 18:E428-30. 2012
    ....
  87. ncbi Review of pharmaceutical applications of N-methyl-2-pyrrolidone
    Abolghasem Jouyban
    Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
    J Pharm Pharm Sci 13:524-35. 2010
    ..This review reveals that NMP is an acceptable pharmaceutical solvent and its efficacy, toxicity, and side effects are comparable with other common solvent...
  88. ncbi The effect of CYP2C19 polymorphism on the safety, tolerability, and pharmacokinetics of tivantinib (ARQ 197): results from a phase I trial in advanced solid tumors
    N Yamamoto
    Division of Thoracic Oncology, Shizuoka Cancer Center, Naga Izumi, Japan
    Ann Oncol 24:1653-9. 2013
    ..In this study, we examined the safety, pharmacokinetics (PK), and preliminary efficacy of tivantinib as a single agent to determine recommended phase II doses (RPIIDs)...
  89. ncbi Drug resistance mutations of HIV type 1 non-B viruses to integrase inhibitors in treatment-naive patients from sub-saharan countries and discordant interpretations
    Marjorie Monleau
    UMI TransVIHMI, Institut de Recherche pour le Developpement, Montpellier, France
    AIDS Res Hum Retroviruses 28:1157-60. 2012
    ..These results illustrated the need of further in vitro and clinical studies involving non-B viruses to better understand the real significance of observed mutations and harmonize interpretations...
  90. pmc Thiophene-degrading Escherichia coli mutants possess sulfone oxidase activity and show altered resistance to sulfur-containing antibiotics
    M J Juhl
    Department of Microbiology, Southern Illinois University, Carbondale 62901
    Appl Environ Microbiol 56:3179-85. 1990
    ..However, the thdA-directed expression of sulfone oxidase activity was not fadR dependent. The thdC and thdD mutations probably protect against the toxicity of thiophene derivatives rather than conferring improved metabolic capability...
  91. ncbi Purinergic neuron-to-glia signaling in the enteric nervous system
    Brian D Gulbransen
    Hotchkiss Brain Institute, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada
    Gastroenterology 136:1349-58. 2009
    ..We investigated whether enteric glia are activated by ATP released from enteric neurons...
  92. ncbi HIV dynamics and integrase inhibitors
    John M Murray
    School of Mathematics and Statistics, University of New South Wales, Sydney, Australia
    Antivir Chem Chemother 19:157-64. 2009
    ..Investigation of HIV RNA and HIV DNA levels with an INI will provide better understanding of how these components are generated and maintained under antiretroviral therapy...
  93. pmc Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness
    Zixin Hu
    Section of Retroviral Therapeutics, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    J Acquir Immune Defic Syndr 55:148-55. 2010
    ..These findings correspond well with the clinical trials data and help explain the temporal pattern of RAL resistance evolution...
  94. ncbi Patterns of adherence to raltegravir-based regimens and the risk of virological failure among HIV-infected patients: the RALTECAPS cohort study
    Guillaume Gras
    Department of Infectious Diseases, Centre Hospitalier Universitaire, Tours, France
    J Acquir Immune Defic Syndr 61:265-9. 2012
    ..05) were both independently associated with virological failure controlling for prior duration of viral suppression. Timely interdose intervals and high levels of adherence to raltegravir are both necessary to control HIV replication...
  95. ncbi A pilot study of abacavir/lamivudine and raltegravir in antiretroviral-naïve HIV-1-infected patients: 48-week results of the SHIELD trial
    Benjamin Young
    Rocky Mountain CARES, Denver, Colorado, USA Health Connections International, Amsterdam, The Netherlands
    HIV Clin Trials 11:260-9. 2010
    ..to evaluate raltegravir plus abacavir/lamivudine in antiretroviral-naïve, HIV-1-infected patients...
  96. pmc Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance
    Robert A Smith
    Department of Pathology, University of Washington, Seattle, Washington 98109, USA
    AIDS 25:2235-41. 2011
    ..Our objectives were to directly compare the susceptibilities of HIV-1 and HIV-2 to raltegravir and to examine the role of mutations in HIV-2 integrase in emergent raltegravir resistance...
  97. ncbi Dynamics of HIV-1 DNA level in highly antiretroviral-experienced patients receiving raltegravir-based therapy
    C Charpentier
    Assistance Publique Hopitaux de Paris, Hopital Europeen Georges Pompidou, Laboratoire de Virologie, 20 rue Leblanc, 75015 Paris, France
    Eur J Clin Microbiol Infect Dis 31:129-33. 2012
    ..The potent action of RAL-containing treatment observed in the CD4 T cells compartment may suggest a pronounced reduced inhibition in the pool of regenerating CD4 T cells on a RAL-based therapy...
  98. ncbi HIV type 1 coreceptor tropism, CCR5 genotype, and integrase inhibitor resistance profiles in Vietnam: implications for the introduction of new antiretroviral regimens
    Quynh Phuong Luu
    Ireland Vietnam Blood Borne Virus Initiative, Dublin, Ireland
    AIDS Res Hum Retroviruses 28:1344-8. 2012
    ..This should help inform policy on the future use of novel antiretrovirals in Vietnam...
  99. pmc Analysis of transmitted resistance to raltegravir and selective pressure among HIV-1-infected patients on a failing HAART in Sao Paulo, Brazil
    N P Mantovani
    Retrovirology Laboratory, Infectious Diseases Division, Federal University of Sao Paulo UNIFESP, Sao Paulo, Brazil
    J Clin Microbiol 50:2122-5. 2012
    ..We found a high frequency of integrase polymorphisms related to the resistance to RAL and sequence stability. Further studies are needed to determine the importance of these polymorphisms to RAL resistance...
  100. ncbi Long-term efficacy and safety of raltegravir, etravirine, and darunavir/ritonavir in treatment-experienced patients: week 96 results from the ANRS 139 TRIO trial
    Catherine Fagard
    INSERM, ISPED, Centre INSERM U897 Epidemiologie Biostatistique, F 33000 Bordeaux, France
    J Acquir Immune Defic Syndr 59:489-93. 2012
    ..CD4 response was maintained (median change of +150 cells/mm(3)). No major toxicity was reported. This triple drug combination showed sustained efficacy and thus should be strongly considered for patients with multiclass-resistant virus...
  101. ncbi HIV integrase inhibitors in ART-experienced patients
    Jose Luis Blanco
    Division of Infectious Diseases, Hospital Clinic, University of Barcelona, Barcelona, Spain
    Curr Opin HIV AIDS 7:415-21. 2012
    ....

Research Grants60

  1. Au/Pt Catalysis in the Synthesis of Elaborate N-Heterocycles: Methodology Develop
    Liming Zhang; Fiscal Year: 2013
    ..including pyrrolo[2,1-a]isoindoles, indolizines, pyrrolizines, 1,2-heterocycle/carbocycle-fused indoles, pyrrolidinones, tetracyclic indolines, and benzoazepinones/benzoazocinones...
  2. Allylsilane Annulation Strategy for Diversity Synthesis
    ANNALIESE FRANZ; Fiscal Year: 2004
    ..rapid access to biologically active heterocycles and carbocycles such as tetrahydrofurans, pyrrolidines, pyrrolidinones, isoxazolidines, quinone derivatives, tetrahydroquinolines, lactams, and cyclopentane rings, as well as ..
  3. NEW DEVELOPMENTS IN ORGANOCOPPER CHEMISTRY
    R Dieter; Fiscal Year: 2004
    ..The synthetic approach to highly substituted pyrrolines, pyrrolidines, and pyrrolidinones involves the reaction of alpha-aminoalkylcuprates with scalemic propargyl substrates in a controlled anti-SN2' ..
  4. Fostriecin and Related Protein Phosphatase Inhibitors
    Dale Boger; Fiscal Year: 2005
    ....
  5. SYNTHESIS OF SPONGISTATIN ANTITUMOR AGENTS
    AMOS SMITH; Fiscal Year: 2007
    ..abstract_text> ..
  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. Design and Synthesis of HIV-1 Protease Inhibitors
    AMOS SMITH; Fiscal Year: 2004
    ....
  9. Heterogeneity of hypoxic Ca2+ release in pulmonary and *
    Yong Xiao Wang; Fiscal Year: 2006
    ..The proposed studies are also of fundamental physiological significance with respect to the regulation of Ca2+ release in other cell types. ..
  10. New Methods for the Synthesis of Neurological Agents
    LARRY OVERMAN; Fiscal Year: 2008
    ..oryzae at 90 nM, suggesting potential antitumor activity. Because of the scarcity of these natural products from their natural sources, little biological evaluation has been carried out. ..
  11. Novel Signaling for Ca2+ and Release in Airway Myocytes
    Yong Xiao Wang; Fiscal Year: 2007
    ..6, and/or RyRs are ubiquitously expressed in a variety of cell types, the mechanistic findings from the proposed study will have general biological and pathological significance for various Ca2+-mediated cellular effects. ..
  12. PRACTICAL CHEMICAL SYNTHESIS OF COMPLEX ALKALOIDS
    LARRY OVERMAN; Fiscal Year: 2009
    ....
  13. Mechanisms for hypoxic Ca2+ release in pulmonary artery myocytes
    Yong Xiao Wang; Fiscal Year: 2010
    ..The findings from this proposal will enhance our understanding of cellular molecular mechanisms for hypoxic [Ca2+]i rise in PASMCs and associated HPV, and may lead to identify potential novel targets to treat pulmonary hypertension. ..
  14. Prevention of post-stroke depression-treatment strategy
    Robert Robinson; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  15. Vascular depression and magnetic stimulation therapy
    Robert Robinson; Fiscal Year: 2005
    ..e. more atrophy lower response rate) and cognitive function. ..
  16. Aging and Sites of Action of Cognition-Enhancing Drugs
    DIANA WOODRUFF PAK; Fiscal Year: 2008
    ..These studies will likely support hypotheses about ACh mechanisms in learning and memory and may identify the cerebellum as an additional site of drug action. [unreadable] [unreadable]..
  17. 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]..
  18. Incarceration and HIV-Infected Inmates
    David A Wohl; Fiscal Year: 2010
    ..Aim 2. Determine the inmate, nurse-counselor and facility characteristics associated with agreeing to HIV VCT. Aim 3. Explore the risks associated with receiving an HIV diagnosis in prison. ..
  19. PKC modulation of calcium current and anesthetic action
    GANESAN KAMATCHI; Fiscal Year: 2007
    ..abstract_text> ..
  20. HIV+ Prison Releases to Access to HIV Care and Services
    David Wohl; Fiscal Year: 2007
    ..2. BCM will reduce intimate and drug related HIV transmission risk behaviors during the year following prison release. ..
  21. DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS
    Arun K Ghosh; Fiscal Year: 2010
    ..This research integrates organic synthesis, protein-ligand x-ray crystallography, molecular modeling and in-depth virus and cell-biological studies to design the next generation of HIV-1 protease inhibitors. ..
  22. ELECTRIC STUDIES OF EXCITATION, SECRETION & CONTRACTION
    Bertil Hille; Fiscal Year: 2007
    ..What are the Ca 2+ buffering and flux properties of these organelles? Our work in these cells concerns processes whose failure leads to disease and whose modulation offers new therapies. ..
  23. Lipid Raft Microdomains in Neutrophil Function
    ROBERT GARY SITRIN; Fiscal Year: 2010
    ..Hopefully, targeting the function of lipid raft microdomains will engender new therapeutic strategies for enhancing antimicrobial defenses and suppressing the deleterious effects of acute inflammation. ..
  24. Predictors of Immunologic Long-term Non-Progression in Children with HIV
    Jintanat Ananworanich; Fiscal Year: 2010
    ..This will be important in deciding when to treat children with antiretroviral therapy. ..
  25. Polymer-Surfactant Therapy in Rat Models of ARDS
    HWILLIAM TAEUSCH; Fiscal Year: 2010
    ..Overall this project will not only develop a promising new therapy of ALI/ARDS, but will also foster basic understanding of mechanisms of surfactant inhibition and ways to overcome it. ..
  26. Induction of HIV-specific Immune Responses
    Rajesh T Gandhi; Fiscal Year: 2010
    ..By understanding the mechanisms by which immune responses against HIV can be augmented, this may lead to improved ways of treating this disease and may help in developing a vaccine to prevent this infection. ..
  27. Myogenic tone in the urethra and its modulation
    Mark Hollywood; Fiscal Year: 2009
    ....
  28. Neurodevelopmental Effects of Antiepileptic Drugs II
    Kimford Meador; Fiscal Year: 2009
    ..The NEAD study has an invaluable cohort, and the results of this continuation proposal will impact the clinical management of women receiving these medications, and improve the health of their children. ..
  29. Mechanisms of Associative Learning in Aging: Mouse Models
    Diana S Woodruff Pak; Fiscal Year: 2010
    ..This proposal has the potential to expand perspectives and devise treatments to facilitate learning and memory in older adults. ..
  30. 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. ..
  31. ETHANOL SENSITIVITY OF NATIVE AND CLONED NMDA RECEPTORS
    John Woodward; Fiscal Year: 2009
    ..Aim 3 will express ethanol-insensitive receptors identified in Aims 1 and 2 in neurons in vitro and in vivo to address which effects of ethanol are mediated by inhibition of NMDA receptors. ..
  32. NOVEL REGULATORY MECHANISMS CONTROLLING BONE REPAIR AND OSTEOPOROSIS
    Peter Friedman; Fiscal Year: 2008
    ..The long-term objective is to identify novel compounds that can be used to treat post-menopausal osteoporosis. [unreadable] [unreadable] [unreadable]..
  33. Differential effects of TARPs on AMPA receptor subunits
    AMY ARAI; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  34. SYNTHESIS OF BIOLOGICALLY ACTIVE NATURAL PRODUCTS
    BARRY SNIDER; Fiscal Year: 2009
    ..In the course of these studies new methods will be developed that are of general utility for preparing drugs more economically. ..
  35. Open Tubular Capillary Electrochromatography/Mass Spectroscopy
    JOSEPH PESEK; Fiscal Year: 2007
    ..This project focuses on providing a means for the analysis of complex samples found in clinical, biological and pharmaceutical applications. [unreadable] [unreadable] [unreadable]..
  36. SEXUAL DIFFERENTIATION OF MOUSE VOMERONASAL FUNCTION
    James Cherry; Fiscal Year: 2004
    ....
  37. DIFFERENCES IN SYNAPTIC VS NONSYNAPTIC AMPA RECEPTORS
    AMY ARAI; Fiscal Year: 2004
    ..Determining which cellular factor stabilizes the low-affinity receptors will constitute the Fifth Aim of this application. ..
  38. Dopamine D4 Receptor in Sustained Attention
    Kehong Zhang; Fiscal Year: 2003
    ..The findings may also provide a pharmacological basis for innovative treatment for ADHD to replace stimulant therapy. ..
  39. Metastasis Competent Genes in Lung Cancer
    Alan Lader; Fiscal Year: 2003
    ..Lader (the PI), Dr. Kwiatkowski, an expert in genetics and molecular biology, and are an expert in metastasis. ..
  40. Development of Etched Modified Capillaries
    JOSEPH PESEK; Fiscal Year: 2002
    ..Microsolv Corporation will undertake a marketing plan to distribute the products for use by companies working in the targeted application areas. ..
  41. MECHANISMS OF T CELL APOPTOSIS DURING HIV1 INFECTION
    Rajesh Gandhi; Fiscal Year: 2002
    ....
  42. CYCLIC AMP/ADENOSINE PATHWAY
    Edwin Jackson; Fiscal Year: 2002
    ..abstract_text> ..
  43. 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. ..
  44. TREATMENT FOR ALCHOLISM: A PRIMATE MODEL
    KELLY COSGROVE; Fiscal Year: 2002
    ..Thus, the effects of bremazocine and naltrexone on ethanol self-administration as a function of sex will be investigated. ..
  45. 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. ..
  46. The Urokinase-CD87 System in Macrophage Activation
    Robert Sitrin; Fiscal Year: 2004
    ....
  47. Mode of Action of Insecticides: Electrophysiological
    Toshio Narahashi; Fiscal Year: 2004
    ..This information will significantly contribute to the development of newer therapeutic means of insecticide intoxication of humans and of more effective and safer insecticides. ..
  48. MECHANISMS AND FUNCTIONS OF ASTROCYTE CALCIUM SIGNALING
    Andrew Charles; Fiscal Year: 2004
    ....
  49. 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. ..
  50. 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. ..
  51. SYNTHESIS OF COCARCINOGENIC DITERPENES
    JAMES RIGBY; Fiscal Year: 2005
    ..These projected investigations should generate substantial new knowledge about complex synthesis as well as providing additional insight into some of the bioactivity exhibited by the subject natural products. ..
  52. TNF Alters Renal Tubular Function in Diabetes
    Frank Gesek; Fiscal Year: 2005
    ..Complementary techniques are used to examine alterations in vivo and at the cellular level. Our studies provide insights into the earliest changes that occur in DT due to the cytokine TNF. ..
  53. SYNTHESIS OF CYTOTOXIC GUAIANOLIDES AND OTHER TERPENOIDS
    JAMES RIGBY; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  54. Regulation and actions of NO in the cardiac plexus
    JEAN HARDWICK; Fiscal Year: 2005
    ..In particular, it will provide important information concerning the regulation and of NO in the control of cardiac function. ..
  55. Ethanol sensitivity--native /recombinant NMDA receptors
    John Woodward; Fiscal Year: 2006
    ..The successful completion of this training plan will substantially enhance the PI's research expertise and his ability to fulfill the goals of his research. ..
  56. Injury-Evoked Regeneration Mechanism in Olfactory System
    Colleen Hegg; Fiscal Year: 2008
    ..Agents that modify the effects of purinergics and purinergic receptors are readily available and could therapeutically modulate cell proliferation and differentiation, in the olfactory system and in the CNS. ..
  57. Purinergic Receptors in Olfactory System
    Colleen Hegg; Fiscal Year: 2003
    ..Because ATP is released during neurotransmission and by noxious stimuli, these studies may elucidate mechanisms for the observed reduction in olfactory sensitivity during exposure to noxious agents. ..
  58. Midcareer Investigator Award /Patient-Oriented Research
    Charles Hicks; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  59. DEVELOPMENT OF LIGAND ASSISTED ASYMMETRIC SYNTHESES
    Arun Ghosh; Fiscal Year: 2001
    ..Besides the broad range of scope and generality, this line of research will provide excellent opportunities to teach and train graduate and undergraduate students in the laboratory. ..