imidazoles

Summary

Summary: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).

Top Publications

  1. ncbi In vivo activation of the p53 pathway by small-molecule antagonists of MDM2
    Lyubomir T Vassilev
    Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Science 303:844-8. 2004
  2. ncbi Identification of RIP1 kinase as a specific cellular target of necrostatins
    Alexei Degterev
    Tufts University, School of Medicine, Department of Biochemistry, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
    Nat Chem Biol 4:313-21. 2008
  3. ncbi Neonicotinoid pesticide reduces bumble bee colony growth and queen production
    Penelope R Whitehorn
    School of Natural Sciences, University of Stirling, Stirling FK9 4LA, UK
    Science 336:351-2. 2012
  4. ncbi Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity
    Sauveur Michel Maira
    Oncology Disease Area, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH4002 Basel, Switzerland
    Mol Cancer Ther 7:1851-63. 2008
  5. ncbi NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations
    Violeta Serra
    Laboratory of Oncology Research, Medical Oncology Service, Vall d Hebron University Hospital, Barcelona, Spain
    Cancer Res 68:8022-30. 2008
  6. pmc AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Cancer Cell 16:401-12. 2009
  7. ncbi Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
    Alexei Degterev
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Chem Biol 1:112-9. 2005
  8. ncbi A protein kinase involved in the regulation of inflammatory cytokine biosynthesis
    J C Lee
    Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406
    Nature 372:739-46. 1994
  9. pmc Interactions between Nosema microspores and a neonicotinoid weaken honeybees (Apis mellifera)
    Cedric Alaux
    INRA, UMR 406 Abeilles et Environnement, Laboratoire Biologie et Protection de l abeille, Site Agroparc, 84914 Avignon, France
    Environ Microbiol 12:774-82. 2010
  10. ncbi p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain
    Shan Xue Jin
    Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA
    J Neurosci 23:4017-22. 2003

Detail Information

Publications354 found, 100 shown here

  1. ncbi In vivo activation of the p53 pathway by small-molecule antagonists of MDM2
    Lyubomir T Vassilev
    Department of Discovery Oncology, Roche Research Center, Hoffmann La Roche, Inc, Nutley, NJ 07110, USA
    Science 303:844-8. 2004
    ..These compounds bind MDM2 in the p53-binding pocket and activate the p53 pathway in cancer cells, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts in nude mice...
  2. ncbi Identification of RIP1 kinase as a specific cellular target of necrostatins
    Alexei Degterev
    Tufts University, School of Medicine, Department of Biochemistry, 136 Harrison Avenue, Boston, Massachusetts 02111, USA
    Nat Chem Biol 4:313-21. 2008
    ..Overall, our data establish necrostatins as the first-in-class inhibitors of RIP1 kinase, the key upstream kinase involved in the activation of necroptosis...
  3. ncbi Neonicotinoid pesticide reduces bumble bee colony growth and queen production
    Penelope R Whitehorn
    School of Natural Sciences, University of Stirling, Stirling FK9 4LA, UK
    Science 336:351-2. 2012
    ..Given the scale of use of neonicotinoids, we suggest that they may be having a considerable negative impact on wild bumble bee populations across the developed world...
  4. ncbi Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity
    Sauveur Michel Maira
    Oncology Disease Area, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH4002 Basel, Switzerland
    Mol Cancer Ther 7:1851-63. 2008
    ..Collectively, the preclinical data show that NVP-BEZ235 is a potent dual PI3K/mTOR modulator with favorable pharmaceutical properties. NVP-BEZ235 is currently in phase I clinical trials...
  5. ncbi NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations
    Violeta Serra
    Laboratory of Oncology Research, Medical Oncology Service, Vall d Hebron University Hospital, Barcelona, Spain
    Cancer Res 68:8022-30. 2008
    ..In summary, NVP-BEZ235 inhibits the PI3K/mTOR axis and results in antiproliferative and antitumoral activity in cancer cells with both wild-type and mutated p110-alpha...
  6. pmc AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Cancer Cell 16:401-12. 2009
    ..Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML...
  7. ncbi Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
    Alexei Degterev
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Chem Biol 1:112-9. 2005
    ..Our study identifies a previously undescribed basic cell-death pathway with potentially broad relevance to human pathologies...
  8. ncbi A protein kinase involved in the regulation of inflammatory cytokine biosynthesis
    J C Lee
    Department of Cellular Biochemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406
    Nature 372:739-46. 1994
    ..Binding of the pyridinyl-imidazole compounds inhibited CSBP kinase activity and could be directly correlated with their ability to inhibit cytokine production, suggesting that the CSBPs are critical for cytokine production...
  9. pmc Interactions between Nosema microspores and a neonicotinoid weaken honeybees (Apis mellifera)
    Cedric Alaux
    INRA, UMR 406 Abeilles et Environnement, Laboratoire Biologie et Protection de l abeille, Site Agroparc, 84914 Avignon, France
    Environ Microbiol 12:774-82. 2010
    ..This provides the first evidences that interaction between an infectious organism and a chemical can also threaten pollinators, interactions that are widely used to eliminate insect pests in integrative pest management...
  10. ncbi p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain
    Shan Xue Jin
    Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA
    J Neurosci 23:4017-22. 2003
    ..Coactivation of p38 in DRG neurons and spinal microglia may contribute to later phases of neuropathic pain...
  11. ncbi Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes
    Hermann Haller
    Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
    N Engl J Med 364:907-17. 2011
    ..We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria...
  12. ncbi Breast-cancer adjuvant therapy with zoledronic acid
    Robert E Coleman
    Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, United Kingdom
    N Engl J Med 365:1396-405. 2011
    ..We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients...
  13. ncbi Applied aspects of neonicotinoid uses in crop protection
    Alfred Elbert
    Bayer CropScience, Development, Agronomic Development, Alfred Nobel Strasse 50, D 40789 Monheim, Germany
    Pest Manag Sci 64:1099-105. 2008
    ..These innovative developments for life-cycle management, jointly with the introduction of generic products, will, within the next few years, turn neonicotinoids into the most important chemical class in crop protection...
  14. pmc Small-molecule inhibitors of the MDM2-p53 protein-protein interaction to reactivate p53 function: a novel approach for cancer therapy
    Sanjeev Shangary
    Comprehensive Cancer Center and Departments of University of Michigan, Ann Arbor, Michigan 48109, USA
    Annu Rev Pharmacol Toxicol 49:223-41. 2009
    ..A number of these small-molecule inhibitors, such as analogs of MI-219 and Nutlin-3, have progressed to advanced preclinical development or early phase clinical trials...
  15. ncbi Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study
    Alison T Stopeck
    University of Arizona, Arizona Cancer Center, Tucson, AZ, USA
    J Clin Oncol 28:5132-9. 2010
    ....
  16. ncbi Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study
    Ezra E W Cohen
    Section of Hematology Oncology, Department of Medicine, University of Chicago Division of Biological Sciences, 5801 S Ellis, Chicago, IL 60637, USA
    J Clin Oncol 26:4708-13. 2008
    ..This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer...
  17. pmc The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma
    Daniel C Cho
    Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Clin Cancer Res 16:3628-38. 2010
    ....
  18. ncbi MDM2 inhibitors for cancer therapy
    Lyubomir T Vassilev
    Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, NJ 07110, USA
    Trends Mol Med 13:23-31. 2007
    ..Here, the new developments in the quest for pharmacological p53 activators are reviewed with an emphasis on small-molecule inhibitors of the p53-MDM2 interaction...
  19. pmc NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas
    Ta Jen Liu
    Department of Neuro Oncology, The University of Texas M D Anderson Cancer Center, Unit 431, 1515 Holcombe Boulevard, Houston, TX 77030
    Mol Cancer Ther 8:2204-10. 2009
    ..These results warrant further development of NVP-BEZ235 for clinical trials for human gliomas or other advanced cancers with altered PI3K/Akt/mTOR signaling...
  20. pmc Dual targeting of phosphoinositide 3-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach in human ovarian carcinoma
    Chintda Santiskulvong
    Division of Gynecologic Oncology, Departments of Obstetrics and Gynecology, UCLA David Geffen School of Medicine, Los Angeles, CA 90095 1740, USA
    Clin Cancer Res 17:2373-84. 2011
    ..This study evaluates the effect of dual PI3K and mTOR inhibition using NVP-BEZ235 in preclinical models of ovarian cancer as a potential novel therapeutic strategy...
  21. ncbi A meta-analysis of experiments testing the effects of a neonicotinoid insecticide (imidacloprid) on honey bees
    James E Cresswell
    School of Biosciences, University of Exeter, Hatherly Laboratories, Prince of Wales Road, Exeter, EX4 4PS, UK
    Ecotoxicology 20:149-57. 2011
    ....
  22. ncbi Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemia
    Francesca Chiarini
    Department of Human Anatomy, University of Bologna, Bologna, Italy
    Cancer Res 70:8097-107. 2010
    ....
  23. ncbi Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma
    Brian I Rini
    Department of Solid Tumor Oncology and Urology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Ave, Desk R35, Cleveland, OH 44195, USA
    J Clin Oncol 27:4462-8. 2009
    ....
  24. ncbi Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results
    Hope S Rugo
    University of California, San Francisco Comprehensive Cancer Center, USA
    J Clin Oncol 23:5474-83. 2005
    ....
  25. pmc S6K1 and 4E-BP1 are independent regulated and control cellular growth in bladder cancer
    Roman Nawroth
    Department of Urology, Klinikum rechts der Isar der Technischen Universitat Munchen, Munich, Germany
    PLoS ONE 6:e27509. 2011
    ..Our data suggest that 4E-BP1 is a potential new target molecule and stratification marker for anti cancer therapy in UC and support the consideration of a multi-targeting approach against PI3K, mTORC1/2 and MAPK...
  26. pmc Evaluation of the long-term efficacy and safety of an imidacloprid 10%/flumethrin 4.5% polymer matrix collar (Seresto®) in dogs and cats naturally infested with fleas and/or ticks in multicentre clinical field studies in Europe
    Dorothee Stanneck
    Bayer Animal Health GmbH BAH, Monheim, Germany
    Parasit Vectors 5:66. 2012
    ....
  27. ncbi Detections of the neonicotinoid insecticide imidacloprid in surface waters of three agricultural regions of California, USA, 2010-2011
    Keith Starner
    California Department of Pesticide Regulation, Environmental Monitoring Branch, 1001 I Street, Sacramento, CA 95812, USA
    Bull Environ Contam Toxicol 88:316-21. 2012
    ..The results indicate that imidacloprid commonly moves offsite and contaminates surface waters at concentrations that could harm aquatic organisms following use under irrigated agriculture conditions in California...
  28. pmc Pesticide exposure in honey bees results in increased levels of the gut pathogen Nosema
    Jeffery S Pettis
    USDA ARS Bee Research Laboratory, Beltsville, MD, USA
    Naturwissenschaften 99:153-8. 2012
    ..Interactions between pesticides and pathogens could be a major contributor to increased mortality of honey bee colonies, including colony collapse disorder, and other pollinator declines worldwide...
  29. ncbi Translocation of neonicotinoid insecticides from coated seeds to seedling guttation drops: a novel way of intoxication for bees
    V Girolami
    Dipartimento di Agronomia Ambientale e Produzioni Vegetali, Entomologia, Universita di Padova, Viale dell Universita 16, 35020 Legnaro, Padova, Italy
    J Econ Entomol 102:1808-15. 2009
    ..When bees consume guttation drops, collected from plants grown from neonicotinoid-coated seeds, they encounter death within few minutes...
  30. ncbi Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II study
    Joan H Schiller
    University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 8852, USA
    J Clin Oncol 27:3836-41. 2009
    ....
  31. ncbi Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3
    Dana D Hu-Lowe
    Department of Cancer Biology, PGRD La Jolla, Pfizer, Inc, San Diego, California 92121, USA
    Clin Cancer Res 14:7272-83. 2008
    ..We provide a comprehensive description of its in vitro characteristics and activities, in vivo antiangiogenesis, and antitumor efficacy and translational pharmacology data...
  32. ncbi Nongenotoxic activation of the p53 pathway as a therapeutic strategy for multiple myeloma
    Thorsten Stühmer
    Department of Internal Medicine II, Division of Hematology and Oncology, University Clinics Würzburg, Germany
    Blood 106:3609-17. 2005
    ..Therefore, MDM2 antagonists may offer a new treatment option for this disease...
  33. ncbi Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemia
    Nicolas Chapuis
    Institut Cochin, Universite Paris Descartes, CNRS UMR8104 INSERM U1016 Service d Hématologie Biologique, Hopital Cochin, AP HP, Paris, France
    Clin Cancer Res 16:5424-35. 2010
    ..We therefore tested, in this study, the antileukemic activity of the dual PI3K/mTOR ATP-competitive inhibitor NVP-BEZ235 compound (Novartis)...
  34. pmc Evaluation of an Actinomycin D/VX-680 aurora kinase inhibitor combination in p53-based cyclotherapy
    Bhavya Rao
    Centre for Oncology and Molecular Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY Tayside, UK
    Oncotarget 1:639-50. 2010
    ..We propose that drugs that incorporate into DNA during S-phase may perform better as second drugs than mitotic poisons in cyclotherapy approaches using LDActD as a cytostatic agent...
  35. ncbi Effect of axitinib (AG-013736) on fatigue, thyroid-stimulating hormone, and biomarkers: a phase I study in Japanese patients
    Toru Mukohara
    National Cancer Center Hospital East, Oncology Hematology, Kashiwa, Japan
    Cancer Sci 101:963-8. 2010
    ..Axitinib 5 mg twice-daily is the recommended starting dose for Japanese patients. This trial is registered with ClinicalTrials.gov, identifier NCT00447005...
  36. ncbi Selective impairment of TLR-mediated innate immunity in human newborns: neonatal blood plasma reduces monocyte TNF-alpha induction by bacterial lipopeptides, lipopolysaccharide, and imiquimod, but preserves the response to R-848
    Ofer Levy
    Channing Laboratory, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 173:4627-34. 2004
    ..Conversely, relative preservation of responses to R-848 may present unique opportunities for augmenting innate and acquired immunity in the human newborn...
  37. ncbi Combination of nutlin-3 and VX-680 selectively targets p53 mutant cells with reversible effects on cells expressing wild-type p53
    C F Cheok
    A STAR, Immunos, Singapore
    Cell Death Differ 17:1486-500. 2010
    ..We highlight the distinct roles of p53 and p73 in mediating the cellular responses to VX-680 and suggest that dual protection by p53 and p73 are needed to guard against endoreduplication and polyploidy...
  38. pmc The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically engineered mouse model of PIK3CA wild-type colorectal cancer
    Jatin Roper
    Division of Gastroenterology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, United States of America
    PLoS ONE 6:e25132. 2011
    ..To examine the in vitro and in vivo efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type colorectal cancer (CRC)...
  39. pmc An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis
    Enrico Giraudo
    Department of Biochemistry and Biophysics, Diabetes Center, and Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA
    J Clin Invest 114:623-33. 2004
    ....
  40. ncbi Inactivation of the p53 pathway in retinoblastoma
    Nikia A Laurie
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 444:61-6. 2006
    ..In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma...
  41. pmc Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235
    Pieter J A Eichhorn
    Medical Oncology Program, Vall d Hebron Institut de Oncologia, Barcelona, Spain
    Cancer Res 68:9221-30. 2008
    ..Our data show that deregulation of the PI3K pathway, either through loss-of-function mutations in PTEN or dominant activating mutations in PIK3CA, leads to lapatinib resistance, which can be effectively reversed by NVP-BEZ235...
  42. pmc Increased AKT S473 phosphorylation after mTORC1 inhibition is rictor dependent and does not predict tumor cell response to PI3K/mTOR inhibition
    Madlaina Breuleux
    Novartis Pharma AG, Novartis Institutes for BioMedical Research, Oncology, Basel, Switzerland
    Mol Cancer Ther 8:742-53. 2009
    ..However, reduced cell viability could not be predicted from biochemical or cellular responses to mTORC1 inhibitors. These data could have implications for the clinical application of phosphatidylinositol 3-kinase/mTOR inhibitors...
  43. ncbi Lethal effect of imidacloprid on the coccinellid predator Serangium japonicum and sublethal effects on predator voracity and on functional response to the whitefly Bemisia tabaci
    Yuxian He
    Institute of Plant Protection, Fujian Academy of Agricultural Sciences, Fuzhou 350013, People s Republic of China
    Ecotoxicology 21:1291-300. 2012
    ..These results hint at the importance of assessing potential effects of imidacloprid on S. japonicum for developing effective integrated pest management programs of B. tabaci in China...
  44. ncbi Crosstalk between the PI3K/mTOR and MEK/ERK pathways involved in the maintenance of self-renewal and tumorigenicity of glioblastoma stem-like cells
    Jun Sunayama
    Department of Molecular Cancer Science Yamagata University School of Medicine, Yamagata, Japan
    Stem Cells 28:1930-9. 2010
    ..Thus, combinational disruption of these pathways would be a rational and effective strategy in the treatment of glioblastoma...
  45. pmc Neonicotinoids in bees: a review on concentrations, side-effects and risk assessment
    Tjeerd Blacquière
    Plant Research International, Wageningen University and Research, Wageningen, The Netherlands
    Ecotoxicology 21:973-92. 2012
    ..Molecular markers may be used to improve risk assessment by a better understanding of the mode of action (interaction with receptors) of neonicotinoids in bees leading to the identification of environmentally safer compounds...
  46. pmc RFID tracking of sublethal effects of two neonicotinoid insecticides on the foraging behavior of Apis mellifera
    Christof W Schneider
    Institut für Bienenkunde, Department of Biological Science, Goethe University, Frankfurt am Main, Germany
    PLoS ONE 7:e30023. 2012
    ..We contribute further information on the understanding of how honeybees are affected by sublethal doses of insecticides...
  47. ncbi A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma
    Karl D Lewis
    University of Colorado Health Sciences Center, Aurora, CO, USA
    Invest New Drugs 29:161-6. 2011
    ..YM155 is a small molecule suppressant of survivin that has been shown in preclinical cell lines, xenograft models and phase I studies to have anti-tumor activity...
  48. ncbi Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848
    Marion Jurk
    Nat Immunol 3:499. 2002
  49. ncbi Synergistic action of a RAF inhibitor and a dual PI3K/mTOR inhibitor in thyroid cancer
    Ning Jin
    Cancer Biology Division, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA
    Clin Cancer Res 17:6482-9. 2011
    ..We tested a novel drug combination targeting RAF, phosphoinositide 3-kinase (PI3K), and mTOR, plus VEGFR2 and RET, in thyroid cancer preclinical models with defined genetic backgrounds...
  50. ncbi NVP-BEZ235 as a new therapeutic option for sarcomas
    Maria C Manara
    Laboratorio di Ricerca Oncologica, Istituto Ortopedico Rizzoli, Bologna, Italy
    Clin Cancer Res 16:530-40. 2010
    ..To evaluate the in vitro and in vivo effects of NVP-BEZ235, a dual pan-phosphoinositide 3-kinase-mammalian target of rapamycin inhibitor in the three most common musculoskeletal tumors (osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma)...
  51. pmc Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells
    Saskia M Brachmann
    Novartis Institutes for BioMedical Research, Oncology Disease Area, CH 4002 Basel, Switzerland
    Proc Natl Acad Sci U S A 106:22299-304. 2009
    ..Overall, this study will provide guidance for patient stratification for forthcoming breast cancer phase II trials for NVP-BEZ235...
  52. ncbi Werner Syndrome as an example of inflamm-aging: possible therapeutic opportunities for a progeroid syndrome?
    Terence Davis
    Department of Pathology, Cardiff University School of Medicine, Wales, United Kingdom
    Rejuvenation Res 9:402-7. 2006
    ..Moreover, drugs that specifically block this inflammation pathway may be possible candidates for therapeutic intervention in WS...
  53. ncbi Structural mechanism of the Pan-BCR-ABL inhibitor ponatinib (AP24534): lessons for overcoming kinase inhibitor resistance
    Tianjun Zhou
    ARIAD Pharmaceuticals Inc, 26 Landsdowne Street, Cambridge, MA 02139, USA
    Chem Biol Drug Des 77:1-11. 2011
    ..The inhibitory mechanism exemplified by ponatinib may have broad relevance to designing inhibitors against other kinases with mutated gatekeeper residues...
  54. pmc Paradoxical suppression of cellular senescence by p53
    Zoya N Demidenko
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Proc Natl Acad Sci U S A 107:9660-4. 2010
    ..Thus, in spite of its ability to induce cell cycle arrest, p53 can act as a suppressor of cellular senescence...
  55. pmc Dual phosphoinositide 3-kinase/mammalian target of rapamycin blockade is an effective radiosensitizing strategy for the treatment of non-small cell lung cancer harboring K-RAS mutations
    Georgia Konstantinidou
    Division of Hematology and Oncology, Simmons Comprehensive Cancer Center, and Hamon Center for Therapeutic Oncology Research, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas TX 75390, USA
    Cancer Res 69:7644-52. 2009
    ..These findings may have general applicability in cancer therapy, because aberrant activation of PI3K occurs frequently in human cancer...
  56. pmc Use of an innovative T-tube maze assay and the proboscis extension response assay to assess sublethal effects of GM products and pesticides on learning capacity of the honey bee Apis mellifera L
    Peng Han
    College of Plant Science and Technology, Hubei Key Laboratory of Utilization of Insect Resources and Sustainable Control of Pests, Huazhong Agricultural University, Shizi Mountain Road, Wuhan 430070, China
    Ecotoxicology 19:1612-9. 2010
    ..The implications of these results are discussed in terms of risks of transgenic CCRI41 cotton crops for honey bees...
  57. ncbi Activation of p38 mitogen-activated protein kinase in spinal microglia is a critical link in inflammation-induced spinal pain processing
    Camilla I Svensson
    Department of Anesthesiology, University of California, San Diego, La Jolla, California, USA
    J Neurochem 86:1534-44. 2003
    ..Taken together, these results indicate that spinal p38 MAPK is involved in inflammation-induced pain and that activated spinal microglia play a direct role in spinal nociceptive processing...
  58. ncbi Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study
    Olivier Rixe
    Pitie Salpetriere Hospital, University of Paris, Paris, France
    Lancet Oncol 8:975-84. 2007
    ..We aimed to assess the activity and safety of axitinib in patients with metastatic renal-cell cancer who had failed on previous cytokine-based treatment...
  59. ncbi Toxicity and nicotinic acetylcholine receptor interaction of imidacloprid and its metabolites in Apis mellifera (Hymenoptera: Apidae)
    R Nauen
    Bayer AG, Agrochemicals Division, Research Insecticides, Building 6220, D 51368 Leverkusen, Germany
    Pest Manag Sci 57:577-86. 2001
    ..The electrophysiological data revealed Hill coefficients of approximately 1, indicating a single binding site responsible for an activation of the receptor and no direct cooperativity or allosteric interaction with a second binding site...
  60. ncbi Activation of p53 by MDM2 antagonists can protect proliferating cells from mitotic inhibitors
    Daisy Carvajal
    Discovery Oncology, Roche Research Center, Hoffmann La Roche Inc, Nutley, New Jersey 07110, USA
    Cancer Res 65:1918-24. 2005
    ..Second, pretreatment with MDM2 antagonists before chemotherapy of tumors with mutant p53 may offer a partial protection to proliferating normal tissues...
  61. ncbi Zoledronic acid and clinical fractures and mortality after hip fracture
    Kenneth W Lyles
    Duke University Medical Center, Durham, NC, USA
    N Engl J Med 357:1799-809. 2007
    ..Mortality is increased after a hip fracture, and strategies that improve outcomes are needed...
  62. ncbi E2F-1 transcriptional activity is a critical determinant of Mdm2 antagonist-induced apoptosis in human tumor cell lines
    M Kitagawa
    Helen Diller Family Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, CA 94115, USA
    Oncogene 27:5303-14. 2008
    ..Furthermore, our results suggest that tumor cells, including Rb mutated cells, which harbor wild-type p53 and high E2F transcriptional activity, could be a good target for Mdm2 antagonist therapy...
  63. ncbi Morbidity and Mortality After Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention: principal results of a prospective randomized controlled study (MOSES)
    Joachim Schrader
    Department of Internal Medicine, St Josefs Hospital, Cloppenburg, Germany
    Stroke 36:1218-26. 2005
    ..In hypertensive stroke patients, for the same level of blood pressure control, eprosartan will be more effective than nitrendipine in reducing cerebrovascular and cardiovascular morbidity and mortality...
  64. ncbi HDM2 antagonist Nutlin-3 disrupts p73-HDM2 binding and enhances p73 function
    L M S Lau
    Division of Hematology Oncology, Department of Paediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada
    Oncogene 27:997-1003. 2008
    ....
  65. pmc Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition
    Anthony C Faber
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 106:19503-8. 2009
    ..These data indicate simultaneous inhibition of PI3K-mTOR and MEK signaling is an effective strategy for treating EGFR mutant lung cancers, including those with acquired resistance to EGFR TKIs...
  66. ncbi Mitogen-activated protein kinase p38 defines the common senescence-signalling pathway
    Hiroaki Iwasa
    Laboratory of Molecular and Cellular Assembly, Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori ku, Yokohama 226 8501, Japan
    Genes Cells 8:131-44. 2003
    ..However, it remains unclear how a common set of senescence phenotypes is indistinguishably induced in various types of senescence...
  67. ncbi Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53
    Tom Van Maerken
    Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
    J Natl Cancer Inst 101:1562-74. 2009
    ..Mutational inactivation of p53 is rare in neuroblastoma tumors at diagnosis and occurs in only a subset of multidrug-resistant neuroblastomas...
  68. ncbi Effects of imidacloprid and deltamethrin on associative learning in honeybees under semi-field and laboratory conditions
    Axel Decourtye
    Laboratoire de Neurobiologie Comparée des Invertébrés, INRA, BP 23, 91440 Bures sur Yvette, France
    Ecotoxicol Environ Saf 57:410-9. 2004
    ....
  69. ncbi The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma
    Philipp Baumann
    Department of Hematology and Oncology Medizinische Klinik Innenstadt, Klinikum der Universitat Munchen, Germany
    Exp Cell Res 315:485-97. 2009
    ..Taken together, inhibition of PI3 kinase/mTOR by NVP-BEZ235 is highly effective and NVP-BEZ235 represents a potential new candidate for targeted therapy in multiple myeloma...
  70. ncbi Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway
    Hiroaki Hemmi
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Immunol 3:196-200. 2002
    ..Imidazoquinoline-induced signaling events were also abolished in both MyD88- and TLR7-deficient mice...
  71. ncbi Abnormal foraging behavior induced by sublethal dosage of imidacloprid in the honey bee (Hymenoptera: Apidae)
    E C Yang
    Department of Entomology, National Chung Hsing University, Taichung, Taiwan
    J Econ Entomol 101:1743-8. 2008
    ..Returning bees also showed delay in their return trips. Our results demonstrated that sublethal dosages of imidacloprid were able to affect foraging behavior of honey bees...
  72. ncbi Differential binding of p53 and nutlin to MDM2 and MDMX: computational studies
    Thomas Leonard Joseph
    Bioinformatics Institute A STAR, Matrix, Singapore
    Cell Cycle 9:1167-81. 2010
    ..These conclusions provide insight into future drug design for dual inhibitors of MDM2 and MDMX, both of which are oncoproteins found overexpressed in many cancers...
  73. pmc MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy
    Kensuke Kojima
    Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Unit 448, Houston, TX 77030, USA
    Blood 106:3150-9. 2005
    ..p53 activation by targeting the p53-MDM2 interaction might offer a novel therapeutic strategy for AML that retain wild-type p53...
  74. ncbi Differential effects between a calcium channel blocker and a diuretic when used in combination with angiotensin II receptor blocker on central aortic pressure in hypertensive patients
    Yoshio Matsui
    Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, 3311 1 Yakushiji, Shimotsuke, Tochigi, Japan
    Hypertension 54:716-23. 2009
    ..0 mg) and hydrochlorothiazide (12.5 mg), despite the lack of a significant difference in brachial systolic BP reduction between the 2 treatments...
  75. ncbi Novel phosphoinositide 3-kinase/mTOR dual inhibitor, NVP-BGT226, displays potent growth-inhibitory activity against human head and neck cancer cells in vitro and in vivo
    Kwang Yu Chang
    Institute of Clinical Medicine, Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China
    Clin Cancer Res 17:7116-26. 2011
    ..To develop a new treatment, we investigated the effect of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in head and neck cancer cells...
  76. ncbi Discovery of OSI-906: a selective and orally efficacious dual inhibitor of the IGF-1 receptor and insulin receptor
    Mark J Mulvihill
    OSI Oncology, OSI Pharmaceuticals, Inc, 41 Pinelawn, Melville, NY 11747, USA
    Future Med Chem 1:1153-71. 2009
    ..The IGF-1 receptor (IGF-1R) has been implicated in the promotion of tumorigenesis, metastasis and resistance to cancer therapies. Therefore, this receptor has become a major focus for the development of anticancer agents...
  77. pmc Rationale, study design, baseline characteristics and blood pressure at 16 weeks in the HONEST Study
    Ikuo Saito
    Keio University Health Center, Kanagawa, Japan
    Hypertens Res 36:177-82. 2013
    ..The HONEST Study is expected to provide evidence showing the relationship between baseline and on-treatment CBP and HBP levels (both first and second measurements) and CV events...
  78. ncbi BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice
    James R Burke
    Department of Immunology, Inflammation and Pulmonary Drug Discovery, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA
    J Biol Chem 278:1450-6. 2003
    ..Thus, the compound is effective against NF-kappa B activation in mice and represents an important tool for investigating the role of IKK in disease models...
  79. ncbi Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial
    Michael Gnant
    Department of Surgery, Comprehensive Cancer Centre Vienna, Medical University of Vienna, A 1090 Vienna, Austria
    Lancet Oncol 12:631-41. 2011
    ..We have now assessed long-term clinical efficacy including disease-free survival and disease outcomes in patients receiving anastrozole or tamoxifen with or without zoledronic acid...
  80. ncbi Bisphosphonates inhibit breast and prostate carcinoma cell invasion, an early event in the formation of bone metastases
    S Boissier
    , , Lyon, France
    Cancer Res 60:2949-54. 2000
    ..These results suggest, therefore, that BPs may be useful agents for the prophylactic treatment of patients with cancers that are known to preferentially metastasize to bone...
  81. ncbi Antitumor effects of YM155, a novel survivin suppressant, against human aggressive non-Hodgkin lymphoma
    Aya Kita
    Drug Discovery Research, Astellas Pharma Inc, Tsukuba shi, Ibaraki, Japan
    Leuk Res 35:787-92. 2011
    ..YM155 increased survival significantly versus rituximab in disseminated Ramos models. This study suggests that YM155 may represent an effective treatment for aggressive lymphomas...
  82. pmc The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats
    Dorothee Stanneck
    Bayer Animal Health GmbH, Leverkusen, Germany
    Parasit Vectors 5:73. 2012
    ..A new polymer matrix collar has recently been developed which is registered for 8 months use in cats and dogs. The basic properties of this collar have been investigated in several in vitro and in vivo studies...
  83. ncbi New risk assessment approach for systemic insecticides: the case of honey bees and imidacloprid (Gaucho)
    Marie Pierre Halm
    Centre d Etude et de Recherche du Médicament de Normandie, 5 rue Vaubenard, 14032 Caen, France
    Environ Sci Technol 40:2448-54. 2006
    ..These data are discussed in the light of field observations made on honey bee mortalities and disappearances. New perspectives are given to better determine the risk posed by systemic insecticides to honey bees...
  84. pmc The combination of RAD001 and NVP-BEZ235 exerts synergistic anticancer activity against non-small cell lung cancer in vitro and in vivo
    Cheng Xiong Xu
    Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, Georgia, United States of America
    PLoS ONE 6:e20899. 2011
    ..Taken together, our results suggest that the combination of RAD001 and BEZ235 is a novel strategy for cancer therapy...
  85. pmc Vertical targeting of the phosphatidylinositol-3 kinase pathway as a strategy for treating melanoma
    Saadia A Aziz
    Department of Pathology, Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut 06510, USA
    Clin Cancer Res 16:6029-39. 2010
    ..Phosphatidylinositol-3 kinase (PI3K) is an important target in melanoma; however, activity of PI3K inhibitors (PI3KI) is limited. Our purpose was to assess mTOR as a cotarget for PI3K...
  86. ncbi Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST Study
    H Eidtmann
    Klinik fur Gynakologie und Geburtshilfe, Universitäts Frauenklinik Kiel, Kiel, Germany
    Ann Oncol 21:2188-94. 2010
    ..Aromatase inhibitors (AIs) are accepted as adjuvant therapy for postmenopausal women (PMW) with hormone-responsive early breast cancer (EBC) with superior efficacy to tamoxifen. However, increased bone loss is associated with AIs...
  87. ncbi Broad spectrum and potent antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models
    Takahito Nakahara
    Institute for Drug Discovery Research, Astellas Pharma, Inc, Tsukuba, Ibaraki, Japan
    Cancer Sci 102:614-21. 2011
    ..The broad and potent antitumor activity presented in the present study is indicative of the therapeutic potential of YM155 in the clinical setting...
  88. ncbi YM155, a novel survivin suppressant, enhances taxane-induced apoptosis and tumor regression in a human Calu 6 lung cancer xenograft model
    Takahito Nakahara
    Institute for Drug Discovery Research, Astellas Pharma Inc, Tsukuba shi, Ibaraki, Japan
    Anticancer Drugs 22:454-62. 2011
    ....
  89. ncbi Mechanism-specific signatures for small-molecule p53 activators
    Ingeborg M M van Leeuwen
    Karolinska Institutet, Stockholm, Sweden
    Cell Cycle 10:1590-8. 2011
    ....
  90. pmc Enhancing the cellular uptake of Py-Im polyamides through next-generation aryl turns
    Jordan L Meier
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Nucleic Acids Res 40:2345-56. 2012
    ..Overall this provides a step forward for controlling the intracellular concentration of Py-Im polyamides that will prove valuable for future applications in which biological potency is essential...
  91. pmc First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial
    Gareth J Morgan
    Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, UK
    Lancet 376:1989-99. 2010
    ..We aimed to establish whether bisphosphonates can affect clinical outcomes in patients with multiple myeloma...
  92. pmc DNA damage response to the Mdm2 inhibitor nutlin-3
    Rajeev Verma
    Department of Molecular and Cell Biology U3125, University of Connecticut, Storrs, CT 06269, USA
    Biochem Pharmacol 79:565-74. 2010
    ..Although this effect may suppress illegitimate homologous recombination repair, it may also increase the risk of clastogenic events...
  93. ncbi Restoration of p53 pathway by nutlin-3 induces cell cycle arrest and apoptosis in human rhabdomyosarcoma cells
    Mitsuru Miyachi
    Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
    Clin Cancer Res 15:4077-84. 2009
    ..In this study, we evaluated whether nutlin-3, a recently developed small-molecule antagonist of MDM2, has an effect on p53-dependent cell cycle arrest and apoptosis in cultured human RMS cell lines...
  94. ncbi Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885
    Alastair J King
    Department of Oncology, MMPD CEDD, GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA
    Cancer Res 66:11100-5. 2006
    ....
  95. ncbi Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1
    G Ambrosini
    Laboratory of New Drug Development, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Oncogene 26:3473-81. 2007
    ..Nutlin-3a therefore may provide a therapeutic benefit in tumors with mutant p53 provided it is combined with chemotherapy...
  96. ncbi Cellular quiescence caused by the Mdm2 inhibitor nutlin-3A
    Lioubov G Korotchkina
    Department of Cell Stress Biology, Roswell Park Cancer Institute, BLSC, Buffalo, NY, USA
    Cell Cycle 8:3777-81. 2009
    ..We discuss that Mdm antagonists could be used in combination with chemotherapy to reversibly arrest normal cells, thus protecting them during chemotherapy of cancer (cyclotherapy)...
  97. ncbi Pharmacological effects of SB 220025, a selective inhibitor of P38 mitogen-activated protein kinase, in angiogenesis and chronic inflammatory disease models
    J R Jackson
    Department of Immunopharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Pharmacol Exp Ther 284:687-92. 1998
    ..Thus, this p38/CSBP MAP kinase inhibitor, which can reduce inflammatory cytokine production and inhibit angiogenesis, is an effective treatment for chronic proliferative inflammatory disease...
  98. ncbi Discrepancy between acute and chronic toxicity induced by imidacloprid and its metabolites in Apis mellifera
    S Suchail
    INRA, Laboratoire de Toxicologie Environnementale, , Avignon, France
    Environ Toxicol Chem 20:2482-6. 2001
    ..For all products tested, bee mortality was induced only 72 h after the onset of intoxication...
  99. ncbi Inhibition of heat-shock protein 27 expression eliminates drug resistance of osteosarcoma to zoledronic acid
    Takeshi Morii
    Department of Orthopedic Surgery, Faculty of Medicine, Kyorin University, 6 20 2 Shinkawa Mitaka Tokyo 161 8611 Japan
    Anticancer Res 30:3565-71. 2010
    ..Although zoledronic acid (ZOL) has been reported to show anti-tumour effects on various malignant tumours, few studies have reported the molecular mechanisms of resistance to ZOL...
  100. pmc Necrostatin-1 reduces histopathology and improves functional outcome after controlled cortical impact in mice
    Zerong You
    Neuroscience Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Cereb Blood Flow Metab 28:1564-73. 2008
    ..The data suggest that necroptosis plays a significant role in the pathogenesis of cell death and functional outcome after TBI and that necrostatin-1 may have therapeutic potential for patients with TBI...
  101. pmc Potent activity of ponatinib (AP24534) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies
    Joseph M Gozgit
    ARIAD Pharmaceuticals, Inc, 26 Landsdowne Street, Cambridge, MA 02139, USA
    Mol Cancer Ther 10:1028-35. 2011
    ..Overall, these results support the investigation of ponatinib in patients with FLT3-ITD-driven AML and other hematologic malignancies driven by KIT, FGFR1, or PDGFRα...

Research Grants62

  1. Triazole hypersensitivity in Candida albicans
    Neeraj Chauhan; Fiscal Year: 2009
    ..mutant retains the wild type levels of sensitivity to other antifungals such as miconazole and ketoconazole (imidazoles), amphotericin B, caspofungin, 5-FC, and a variety of other inhibitors such as Congo red, calcofluor white, ..
  2. Tyrosinase Model Complexes using Imidazole Ligands
    JOHN BRANNON GARY; Fiscal Year: 2013
    ..studies in the field have used non-biologically relevant ligands such as pyridine, pyrazine, or alkyl protected imidazoles. This proposal aims to use ligands more biologically relevant ligands in model complexes through computational ..
  3. Planning Grant for the Efficacy of Auranofin for the Treatment of Amebiasis
    Sharon L Reed; Fiscal Year: 2012
    ..b>Imidazoles, particularly metronidazole, are the single class of drugs used worldwide for treatment...
  4. Novel Therapeutics for Class B Protozoa
    Sharon L Reed; Fiscal Year: 2012
    ..new molecular targets for drug development is key for future therapy as resistance to the main class of drugs, imidazoles, has been detected in both parasites...
  5. Phase II Environmentally greener, efficient, and safe synthetic platform for the
    PAUL MATTHEW HERRINTON; Fiscal Year: 2011
    ..Expand the portfolio of borylated pyridine derivatives and add quinolines, pyrazines, pyrimidines, diazenes, imidazoles, pyrazoles, oxazoles, etc. Produce oxidized products (e.g. hydroxyquinolines) where applicable. 2...
  6. ELECTROSTATICS AND DYNAMICS IN MYOGLOBIN MUTANTS
    STEVEN BOXER; Fiscal Year: 2003
    ..the proximal histidine in Mb with a very wide range of small organic ligands including methyl-substituted imidazoles, pyridine, phenol, furan, thiophene, and ethanethiol...
  7. Genetic Analysis of Echinocandin Sensitivity
    Santosh Katiyar; Fiscal Year: 2004
    ..Until recently, available antifungals were limited by systemic toxicity (polyenes and imidazoles), lack of fungicidal activity (triazoles and flucytosine), or narrow spectrum (allylamines)...
  8. NOVEL CHARACTERISTICS OF 1-IMIDAZOLE ENZYME INDUCTION
    Michael Franklin; Fiscal Year: 1990
    ..N-substituted imidazoles are best known for their antimycotic activity...
  9. SMALL MOLECULE ORPHANIN FQ/NOCICEPTIN RECEPTOR LIGANDS
    Richard Houghten; Fiscal Year: 2000
    ..Examples of the heterocyclic libraries include bicyclic guanidines, substitute isoquinilones, indole-imidazoles, quinazolinones, cyclic ureas and hydantoins...
  10. BIOTECHNOLOGY RESOURCE IN PULSED EPR SPECTROSCOPY
    Jack Peisach; Fiscal Year: 1999
    ..and ESEEM studies demonstrate inequivalence in electron nuclear coupling with the individual copper-coordinated imidazoles that constitute the metal binding site...
  11. Analogs: Unique Probes for Cannabinoid Receptors
    Brian Thomas; Fiscal Year: 2006
    ..modification of each substituent position of the pyrazole nucleus and also include alternative pyrazole, imidazoles and pyrazolo [l,5-f] phenanthridine ring systems where the substituents may or may not maintain the original ..
  12. IDENTIFICATION OF RECEPTOR SPECIFIC OPIOID LIGANDS
    Richard Houghten; Fiscal Year: 2002
    ..peptidomimetics and over 4 million low molecular weight acyclic and heterocyclic compounds, including indole-imidazoles, quinazolinones, and bicyclic guanidines...
  13. METALLOENZYME SITES--SYNTHESES AND BIOMIMETIC CHEMISTRY
    TEDDY TRAYLOR; Fiscal Year: 1990
    ..hemerythrin, hemocyanine, and azurine will be synthesized by attaching the appropriate numbers of imidazoles, thiol groups, and/or thioether groups to bicyclic organic compounds so that all the metal liganding groups are ..
  14. 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. ..
  15. 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. ..
  16. 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. ..
  17. Therapeutic Modulation of COX-2-induced Immunosuppression in Metastatic RCC
    Brian Rini; Fiscal Year: 2008
    ..This project will have broad implications for the immunoregulation of cancer and how expression and modulation of COX-2 expression influences the immune response to cancer. [unreadable] [unreadable] [unreadable]..
  18. Oxidative Stress and Genetics of Prehypertension
    Shawna Nesbitt; Fiscal Year: 2004
    ..abstract_text> ..
  19. EPR Sample-cell-Resonator Design and Construction
    James Hyde; Fiscal Year: 2008
    ..Work proposed here will improve the quality of data obtained in these experiments. [unreadable] [unreadable] [unreadable]..
  20. Understanding the Impact of Multiple Symptoms: A Symptom Burden Consortium
    Charles Cleeland; Fiscal Year: 2006
    ..The document will be a collaborative effort among consortium participants, and will be submitted to a leading scientific peer-reviewed journal. [unreadable] [unreadable] [unreadable] [unreadable]..
  21. Gram-Negative Sepsis: Pharmacophore-Based Therapeutics
    Sunil David; Fiscal Year: 2007
    ..abstract_text> ..
  22. Hydrophobic Polyamine Amides as Anti-Endotoxin Agents
    Sunil David; Fiscal Year: 2007
    ..The toxicity of the compounds will be systematically determined in a panel of in vitro assays. These studies will serve to generate data for anticipated IND submissions. [unreadable] [unreadable]..
  23. Functional Materials Through Bottom-Up Self-Assembly - 2007 Supramolecules & Asse
    John Texter; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  24. RECURRENT HEPATITIS B AFTER LIVER TRANSPLANTATION
    Anna Lok; Fiscal Year: 2007
    ..abstract_text> ..
  25. ITEM BANKING AND CAT FOR QUALITY OF LIFE OUTCOMES
    David Cella; Fiscal Year: 2008
    ..We will also monitor treatment/management changes, and evaluate acceptability of computer assessments and the perceived benefits of the recommendations. ..
  26. Angll and PPARy/LXR in Atherosclerosis
    Willa Hsueh; Fiscal Year: 2008
    ..4) Determine whether PPARgamma ligands or LXRaalpha ligands can induce regression of established atherosclerosis. ..
  27. Modifications of Small Heat Shock Proteins in the Lens
    RAM NAGARAJ; Fiscal Year: 2009
    ..These studies will improve our understanding of the interplay between sHsps and metabolic pathways, and they will help us to define the role of sHsps in apoptosis of lens epithelial cells and the implications for cataract formation. ..
  28. Macrophage defense againt M. tuberculosis
    Jennifer Wang; Fiscal Year: 2008
    ..abstract_text> ..
  29. Molecular Basis Of Renal Cell Carcinoma Response to SU11428
    Robert J Motzer; Fiscal Year: 2011
    ..These tumor and cell line-based studies lay a foundation for further molecular studies aimed at understanding the sensitivity/resistance of RCC to SU11248. ..
  30. Development of Cellular Assays of Dengue Virus Infection
    Priscilla Yang; Fiscal Year: 2008
    ..These inhibitors can be used to study how dengue virus interacts with its host, and they may also be useful in developing therapies for the treatment of dengue virus infections. [unreadable] [unreadable] [unreadable]..
  31. Plasminogen activators and cerebral ischemic injury
    William M Armstead; Fiscal Year: 2010
    ....
  32. DIFFUSION MRI AS BIOMARKER FOR THERAPY RESPONSE IN BREAST CANCER METASTASES
    Alison T Stopeck; Fiscal Year: 2010
    ....
  33. IDIOPATHIC OSTEOPOROSIS IN PREMENOPAUSAL WOMEN
    Elizabeth Shane; Fiscal Year: 2009
    ..The results of these studies will have important therapeutic implications for the diagnosis and management of this disorder. ..
  34. RAAS, Inflammation & Post-Operative Atrial Fibrillation
    Nancy Brown; Fiscal Year: 2009
    ..abstract_text> ..
  35. Glycation and mu dicarbonyls in diabetic complications
    Paul Beisswenger; Fiscal Year: 2006
    ..These exciting research projects, and new ones on the horizon, combined with the proposed mentoring/training program offers real opportunities of attracting and rewarding a new generation of clinical investigators. ..
  36. Mechanisms of CVD and Endothelial Dysfunction in Obesity
    Willa Hsueh; Fiscal Year: 2006
    ..Early intervention is critical if we are to prevent these two major diseases, which may, indeed, be the same disease. ..
  37. Amine N-Oxygenation by FMO3 and FMO4
    John Cashman; Fiscal Year: 2005
    ..Such fundamental information will be useful in the development of safer drugs, the prevention of adverse drug reactions and the protection of humans from disease. ..
  38. Role of MMPs in AngII induced abdominal aortic aneurysms
    Alan Daugherty; Fiscal Year: 2005
    ..The significance of this research relates to delineation of mechanism for AA formation and maturation, with emphasis on potential development of pharmacological treatments of the disease. ..
  39. Novel Leads for the Therapy of Gram-Positive Sepsis
    Sunil David; Fiscal Year: 2004
    ..This is to demonstrate that inhibition of cytokine release, if observed, is attributable to the blockade of the cellular recognition of lipoteichoic acid. ..
  40. Sterol Biosynthesis in Trypanosomatid Parasites
    Frederick Buckner; Fiscal Year: 2004
    ..The drugs discovered in this research program will hopefully provide better future treatment for patients with these devastating diseases. ..
  41. ANGIOTENSIN II AND MITOGEN ACTIVATED PROTEIN KINASE
    Willa Hsueh; Fiscal Year: 2003
    ..5) Investigate the mechanism of transcription at regulation of PAI-1 by hyperglycemia AngII, insulin and the MAPK inhibitor in cultured rat cardiac fibroblasts. ..
  42. CLINICAL TRIALS AND MENTORING IN ONCOLOGY RESEARCH
    Robert Motzer; Fiscal Year: 2003
    ..One recently joined staff at MSKCC in the Genito-urinary Section. Mentoring of clinical trials is extended beyond fellowship to junior faculty members. ..
  43. BROADBAND EPR SPECTROMETER WITH DIGITAL SUBSAMPLING
    James Hyde; Fiscal Year: 2002
    ..It is the only method that can detect the formation of free radicals in biology unambiguously. It contributes to health-related research at the basic fundamental level. ..
  44. MOLECULAR EVOLUTION OF ENTERIC BACTERIOCINS
    Margaret Riley; Fiscal Year: 2002
    ..we gain regarding the natural role of bacteriocins, and the defenses raised against them within bacterial communities, can be directly applied to the rational application of novels antimicrobials to human health issues ..
  45. DEVELOPMENT OF BIOMEDICAL ESR INSTRUMENTATION
    James Hyde; Fiscal Year: 2002
    ..The investigator asserts that only on such a foundation can a rational approach to improved human health be based. ..
  46. CELL GROWTH, NA/H EXCHANGE, AND CYCLINS IN IDDM PATIEN
    Daniel Batlle; Fiscal Year: 2002
    ....
  47. Novel High-throghput Assay:Angiogenesis Inhibitors (RMI)
    Sunil David; Fiscal Year: 2004
    ..Promising compounds will be examined in greater detail with respect to details of the physical interactions with heparin. Further biological activity will be ascertained in chicken chorioallantoic membrane assays. ..
  48. ENZYMATIC CONTROLS OF NONENZYMATIC GLYCATION
    Paul Beisswenger; Fiscal Year: 2005
    ..Increased understanding of the role played by enzymatic mechanisms that determine levels of dicarbonyls and Amadori products and their resulting AGEs is essential if we are to find effective strategies to prevent diabetic nephropathy. ..
  49. VIRAHEP-C Clinical Center
    Anna Lok; Fiscal Year: 2005
    ..abstract_text> ..
  50. Rational Development of Endotoxin Sequestering Agents
    Sunil David; Fiscal Year: 2006
    ..Highly active molecules will be further tested in two murine models of gram-negative sepsis. The toxicity of the compounds will be systematically determined in a panel of in vitro assays. ..
  51. Multifunctional Nanoparticles for Intracellular Delivery
    Stefan Franzen; Fiscal Year: 2006
    ..5. Develop strategies for covalent attachment of proteins and oligonucleotides to nanoparticles. 6. Determine of the efficiency of regulated in vitro protein expression using a well-characterized model system. ..
  52. New Opioids for Alcoholism
    John Cashman; Fiscal Year: 2006
    ..The potential commercial application of the work is that the research could lead to a 'blockbuster' drug product. [unreadable] [unreadable]..
  53. BD Biosciences FACS Canto Flow Cytometer
    LAWRENCE LAMB; Fiscal Year: 2006
    ..The laboratory will require an instrument that will serve the laboratory in the development and execution of advanced cell therapy trials. [unreadable] [unreadable]..
  54. POTASSIUM CHANNELS AND CEREBRAL HEMODYNAMICS AFTER BRAIN
    William Armstead; Fiscal Year: 2005
    ..These studies may lead to therapies for brain injured children. ..
  55. Modeling Oxygen Activation by Monocopper Enzyme Sites
    BENJAMIN GHERMAN; Fiscal Year: 2006
    ....
  56. Mechanisms and Treatment of Cancer-Related Symptoms Conf
    Charles Cleeland; Fiscal Year: 2005
    ..The conference should also be of interest to pharmaceutical companies that are developing "pipeline" drugs for symptom control and supportive care. ..
  57. Translation Research in Plasmodium vivax
    Socrates Herrera; Fiscal Year: 2005
    ..abstract_text> ..
  58. PAI-1 and The Vascular Toxicity of Aldosterone
    Nancy Brown; Fiscal Year: 2005
    ..This multi-disciplinary approach will generate new information regarding the role of aldosterone in vascular toxicity and, thus, improve our ability to prevent and treat cardiovascular disease. ..
  59. Novel Pathways of AGE Formation in Diabetes
    RAM NAGARAJ; Fiscal Year: 2005
    ..Our study is expected to provide novel insights into AGE formation in diabetes and may lead to new pharmacological agents to prevent AGE formation and complications in diabetes. ..
  60. Prevention of Osteoporosis after Transplantation
    Elizabeth Shane; Fiscal Year: 2002
    ..We are now applying for 3 years of support to complete 12 months of observation on those subjects enrolled after March, 2001 and to complete an additional 24 months of follow-up on enrolled participants. ..