pyridines

Summary

Summary: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.

Top Publications

  1. ncbi Sorafenib in advanced hepatocellular carcinoma
    Josep M Llovet
    Barcelona Clinic Liver Cancer Group, Institut d Investigacions Biomediques August Pi i Sunyer, Centro de Investigaciones en Red de Enfermedades Hepáticas y Digestivas Hospital Clínic Barcelona, Barcelona
    N Engl J Med 359:378-90. 2008
  2. ncbi Dabigatran versus warfarin in patients with atrial fibrillation
    Stuart J Connolly
    Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
    N Engl J Med 361:1139-51. 2009
  3. ncbi BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis
    Scott M Wilhelm
    Bayer Pharmaceuticals Corporation, West Haven, Connecticut 06516, USA
    Cancer Res 64:7099-109. 2004
  4. ncbi Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial
    Ann Lii Cheng
    National Taiwan University Hospital, Taipei, Taiwan
    Lancet Oncol 10:25-34. 2009
  5. ncbi A ROCK inhibitor permits survival of dissociated human embryonic stem cells
    Kiichi Watanabe
    Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650 0047, Japan
    Nat Biotechnol 25:681-6. 2007
  6. ncbi Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling
    Scott M Wilhelm
    Bayer HealthCare Pharmaceuticals, 340 Changebridge Road, P O Box 1000, Montville, NJ 07045 1000, USA
    Mol Cancer Ther 7:3129-40. 2008
  7. ncbi Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5
    Li Liu
    Department of Cancer Biology, Bayer HealthCare Pharmaceuticals, West Haven, Connecticut 06516, USA
    Cancer Res 66:11851-8. 2006
  8. ncbi Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension
    M Uehata
    Discovery Research Tokyo, Yoshitomi Pharmaceutical Industries Ltd, Saitama, Japan
    Nature 389:990-4. 1997
  9. ncbi Sorafenib in advanced clear-cell renal-cell carcinoma
    Bernard Escudier
    Department of Medicine, Institut Gustave Roussy, Villejuif, France
    N Engl J Med 356:125-34. 2007
  10. ncbi Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity
    Scott M Wilhelm
    Bayer HealthCare Pharmaceuticals, Montville, NJ, USA
    Int J Cancer 129:245-55. 2011

Detail Information

Publications376 found, 100 shown here

  1. ncbi Sorafenib in advanced hepatocellular carcinoma
    Josep M Llovet
    Barcelona Clinic Liver Cancer Group, Institut d Investigacions Biomediques August Pi i Sunyer, Centro de Investigaciones en Red de Enfermedades Hepáticas y Digestivas Hospital Clínic Barcelona, Barcelona
    N Engl J Med 359:378-90. 2008
    ..A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma...
  2. ncbi Dabigatran versus warfarin in patients with atrial fibrillation
    Stuart J Connolly
    Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada
    N Engl J Med 361:1139-51. 2009
    ..Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor...
  3. ncbi BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis
    Scott M Wilhelm
    Bayer Pharmaceuticals Corporation, West Haven, Connecticut 06516, USA
    Cancer Res 64:7099-109. 2004
    ..These data demonstrate that BAY 43-9006 is a novel dual action RAF kinase and VEGFR inhibitor that targets tumor cell proliferation and tumor angiogenesis...
  4. ncbi Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial
    Ann Lii Cheng
    National Taiwan University Hospital, Taipei, Taiwan
    Lancet Oncol 10:25-34. 2009
    ....
  5. ncbi A ROCK inhibitor permits survival of dissociated human embryonic stem cells
    Kiichi Watanabe
    Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN, Kobe 650 0047, Japan
    Nat Biotechnol 25:681-6. 2007
    ..We demonstrate that the protective ability of Y-27632 enables SFEB-cultured hES cells to survive and differentiate into Bf1(+) cortical and basal telencephalic progenitors, as do SFEB-cultured mouse ES cells...
  6. ncbi Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling
    Scott M Wilhelm
    Bayer HealthCare Pharmaceuticals, 340 Changebridge Road, P O Box 1000, Montville, NJ 07045 1000, USA
    Mol Cancer Ther 7:3129-40. 2008
    ..In particular, preclinical evidence that supports the different mechanisms of action of sorafenib is discussed...
  7. ncbi Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5
    Li Liu
    Department of Cancer Biology, Bayer HealthCare Pharmaceuticals, West Haven, Connecticut 06516, USA
    Cancer Res 66:11851-8. 2006
    ....
  8. ncbi Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension
    M Uehata
    Discovery Research Tokyo, Yoshitomi Pharmaceutical Industries Ltd, Saitama, Japan
    Nature 389:990-4. 1997
    ..Our findings indicate that p160ROCK-mediated Ca2+ sensitization is involved in the pathophysiology of hypertension and suggest that compounds that inhibit this process might be useful therapeutically...
  9. ncbi Sorafenib in advanced clear-cell renal-cell carcinoma
    Bernard Escudier
    Department of Medicine, Institut Gustave Roussy, Villejuif, France
    N Engl J Med 356:125-34. 2007
    ..We conducted a phase 3, randomized, double-blind, placebo-controlled trial of sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma...
  10. ncbi Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity
    Scott M Wilhelm
    Bayer HealthCare Pharmaceuticals, Montville, NJ, USA
    Int J Cancer 129:245-55. 2011
    ..These data demonstrate that regorafenib is a well-tolerated, orally active multikinase inhibitor with a distinct target profile that may have therapeutic benefit in human malignancies...
  11. ncbi Inhibition of the hedgehog pathway in advanced basal-cell carcinoma
    Daniel D Von Hoff
    Translational Genomics Research Institute and Scottsdale Healthcare, Scottsdale, AZ, USA
    N Engl J Med 361:1164-72. 2009
    ..In a phase 1 clinical trial, we assessed the safety and pharmacokinetics of GDC-0449, a small-molecule inhibitor of SMO, and responses of metastatic or locally advanced basal-cell carcinoma to the drug...
  12. 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...
  13. ncbi Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449
    Charles M Rudin
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA
    N Engl J Med 361:1173-8. 2009
    ....
  14. ncbi Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma
    Robert L Yauch
    Genentech, South San Francisco, CA 94080, USA
    Science 326:572-4. 2009
    ..These findings show that acquired mutations in a serpentine receptor with features of a G protein-coupled receptor can serve as a mechanism of drug resistance in human cancer...
  15. pmc Small molecule modulation of Smoothened activity
    James K Chen
    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 99:14071-6. 2002
    ..The mechanistic differences between the Smo antagonists may be useful in the therapeutic manipulation of Hh signaling...
  16. ncbi Efficacy and safety of vismodegib in advanced basal-cell carcinoma
    Aleksandar Sekulic
    Mayo Clinic, Scottsdale, AZ 85259, USA
    N Engl J Med 366:2171-9. 2012
    ..A phase 1 study of vismodegib (GDC-0449), a first-in-class, small-molecule inhibitor of the hedgehog pathway, showed a 58% response rate among patients with advanced basal-cell carcinoma...
  17. ncbi Discovery and development of sorafenib: a multikinase inhibitor for treating cancer
    Scott Wilhelm
    Department of Cancer Research, Bayer Pharmaceuticals Corp, West Haven, Connecticut 06516, USA
    Nat Rev Drug Discov 5:835-44. 2006
    ....
  18. ncbi Dabigatran versus warfarin in the treatment of acute venous thromboembolism
    Sam Schulman
    Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, ON, Canada
    N Engl J Med 361:2342-52. 2009
    ..The direct oral thrombin inhibitor dabigatran has a predictable anticoagulant effect and may be an alternative therapy to warfarin for patients who have acute venous thromboembolism...
  19. 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...
  20. pmc Phase II trial of sorafenib in advanced thyroid cancer
    Vandana Gupta-Abramson
    Developmental TherapeuticsProgram of the Abramson CancerCenter, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Clin Oncol 26:4714-9. 2008
    ....
  21. ncbi Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity
    Joanne van Ryn
    Department of Drug Discovery Support, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach an der Riss, Germany
    Thromb Haemost 103:1116-27. 2010
    ....
  22. ncbi Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors
    Patricia M LoRusso
    Karmanos Cancer Institute, Detroit, Michigan Johns Hopkins University, Baltimore, Maryland, USA
    Clin Cancer Res 17:2502-11. 2011
    ..This phase I trial assessed GDC-0449 treatment in patients with solid tumors refractory to current therapies or for which no standard therapy existed...
  23. pmc Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis
    T Eisen
    Royal Marsden Hospital, Downs Road, Surrey SMT 5PT, UK
    Br J Cancer 95:581-6. 2006
    ..i.d.). Ongoing trials in advanced melanoma are evaluating sorafenib combination therapies...
  24. ncbi Efficacy of pyriproxyfen-treated nets in sterilizing and shortening the longevity of Anopheles gambiae (Diptera: Culicidae)
    Kazunori Ohashi
    Health and Crop Sciences Research Laboratory, Sumitomo Chemical Company, Ltd, Hyogo 665 8555, Japan
    J Med Entomol 49:1052-8. 2012
    ....
  25. pmc Phase II study of sorafenib in patients with metastatic or recurrent sarcomas
    Robert G Maki
    Melanoma Sarcoma Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Howard 909, New York, NY 10065, USA
    J Clin Oncol 27:3133-40. 2009
    ..Further evaluation of sorafenib in these and possibly other sarcoma subtypes appears warranted, presumably in combination with cytotoxic or kinase-specific agents...
  26. ncbi Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial
    Lars Wallentin
    Uppsala Clinical Research Centre, Uppsala University, Uppsala, Sweden
    Lancet 376:975-83. 2010
    ..We aimed to investigate the primary and secondary outcomes of the RE-LY trial in relation to each centre's mean TTR (cTTR) in the warfarin population...
  27. ncbi Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts
    David W Fry
    Cancer Pharmacology, Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA
    Mol Cancer Ther 3:1427-38. 2004
    ..The results indicate that inhibition of Cdk4/6 alone is sufficient to cause tumor regression and a net reduction in tumor burden in some tumors...
  28. ncbi Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate
    Joachim Stangier
    Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany
    Clin Pharmacokinet 47:285-95. 2008
    ....
  29. pmc Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors
    Valerie B Caraiscos
    Institute of Medical Science, Department of Anesthesia, University of Toronto, Toronto, ON, Canada M5S 1A8
    Proc Natl Acad Sci U S A 101:3662-7. 2004
    ....
  30. pmc Over-expression of a cytochrome P450 is associated with resistance to pyriproxyfen in the greenhouse whitefly Trialeurodes vaporariorum
    Nikos Karatolos
    Rothamsted Research, Harpenden, Hertfordshire, United Kingdom
    PLoS ONE 7:e31077. 2012
    ..Although there are reports of insects evolving resistance to pyriproxyfen, the underlying resistance mechanism(s) are poorly understood...
  31. pmc PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro
    Richard S Finn
    Department of Medicine, Division of Hematology Oncology, Geffen School of Medicine at UCLA, 10833 Le Conte Ave, 11 934 Factor Bldg, Los Angeles, CA 90095, USA
    Breast Cancer Res 11:R77. 2009
    ..To identify predictors of response, we determined the in vitro sensitivity to PD 0332991 across a panel of molecularly characterized human breast cancer cell lines...
  32. ncbi Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer
    Keith T Flaherty
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA
    Clin Cancer Res 18:568-76. 2012
    ....
  33. pmc The GLI genes as the molecular switch in disrupting Hedgehog signaling in colon cancer
    Tapati Mazumdar
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA
    Oncotarget 2:638-45. 2011
    ....
  34. ncbi Randomized, placebo-controlled, phase III study of first-line oxaliplatin-based chemotherapy plus PTK787/ZK 222584, an oral vascular endothelial growth factor receptor inhibitor, in patients with metastatic colorectal adenocarcinoma
    J Randolph Hecht
    David Geffen School of Medicine at University of California, Los Angeles, Santa Monica, CA 90404, USA
    J Clin Oncol 29:1997-2003. 2011
    ....
  35. ncbi Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models
    Yong S Chang
    Department of Protein Therapeutics, Bayer Research Center, Bayer HealthCare, Pharmaceuticals, 400 Morgan Lane, West Haven, CT 06516, USA
    Cancer Chemother Pharmacol 59:561-74. 2007
    ..The effect of sorafenib on tumor growth and tumor histology was assessed in both ectopic and orthotopic mouse models of RCC...
  36. pmc VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer
    Weon Kyoo You
    Cardiovascular Research Institute, Comprehensive Cancer Center, and Department of Anatomy, University of California, San Francisco, CA 94143, USA
    Cancer Res 71:4758-68. 2011
    ....
  37. ncbi Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial
    Bengt I Eriksson
    Department of Orthopaedic Surgery, Sahlgrenska University Hospital Ostra, Gothenburg, Sweden
    Lancet 370:949-56. 2007
    ..After hip replacement surgery, prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism. Our aim was to assess the oral, direct thrombin inhibitor dabigatran etexilate for such prophylaxis...
  38. ncbi Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran
    Michael D Ezekowitz
    Lankenau Institute for Medical Research and The Heart Center, Wynnewood, PA, USA
    Am Heart J 157:805-10, 810.e1-2. 2009
    ..The worldwide site distribution and broad range of stroke risk further increase the general applicability of the trial. Results are expected in 2009...
  39. ncbi Phase II study of sorafenib in patients with advanced hepatocellular carcinoma
    Ghassan K Abou-Alfa
    Memorial Sloan Kettering Cancer Center, York, NY 10022, USA
    J Clin Oncol 24:4293-300. 2006
    ..This phase II study of sorafenib, an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases, assessed efficacy, toxicity, pharmacokinetics, and biomarkers in advanced hepatocellular carcinoma (HCC) patients...
  40. ncbi Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK)
    J Jean Cui
    La Jolla Laboratories, Pfizer Worldwide Research and Development, San Diego, California 92121, USA
    J Med Chem 54:6342-63. 2011
    ....
  41. ncbi The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans
    Stefan Blech
    Boehringer Ingelheim Pharma GmbH and Co KG, Department of Drug Metabolism and Pharmacokinetics, Biberach, Germany
    Drug Metab Dispos 36:386-99. 2008
    ..o. administration of dabigatran etexilate and that the potential for clinically relevant interactions between dabigatran and drugs metabolized by cytochrome P450 is low...
  42. pmc The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects
    Joachim Stangier
    Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim, Germany
    Br J Clin Pharmacol 64:292-303. 2007
    ..Two double-blind, randomized trials were undertaken to investigate the pharmacokinetics (PK), pharmacodynamics (PD) and tolerability of orally administered dabigatran etexilate in healthy male subjects...
  43. ncbi Indirect comparisons of new oral anticoagulant drugs for efficacy and safety when used for stroke prevention in atrial fibrillation
    Gregory Y H Lip
    University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK
    J Am Coll Cardiol 60:738-46. 2012
    ..This study sought to perform an indirect comparison analysis of dabigatran etexilate (2 doses), rivaroxaban, and apixaban for their relative efficacy and safety against each other...
  44. ncbi Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma
    John P Leonard
    Department of Medicine, Division of Hematology Oncology, Weill Cornell Medical College, New York, NY, USA
    Blood 119:4597-607. 2012
    ..This study is registered at www.clinicaltrials.gov under identifier NCT00420056...
  45. ncbi Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study
    Jean Michel Molina
    Department of Infectious Diseases, Saint Louis Hospital, AP HP, Paris University of Paris Diderot, Paris 7, France
    Lancet 372:646-55. 2008
    ..We compared these two combinations directly in treatment-naive patients...
  46. pmc Phase II trial of sorafenib in metastatic thyroid cancer
    Richard T Kloos
    Ohio State University, Department of Internal Medicine, Molecular Virology, Immunology, and Genetics, Pathology, Radiology, Center for Biostatistics, Ohio State University, Columbus, OH 43210, USA
    J Clin Oncol 27:1675-84. 2009
    ..Based on the pivotal role of Ras-Raf-MAP-ERK signaling and vascular endothelial growth factor (VEGF) in papillary thyroid cancer (PTC), we conducted a phase II clinical trial of sorafenib targeting RAF and VEGF receptor kinases in PTC...
  47. 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...
  48. 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...
  49. ncbi Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo
    David B Ring
    Chiron Corporation, Emeryville, California, USA
    Diabetes 52:588-95. 2003
    ..Collectively, our results suggest that these selective GSK-3 inhibitors may be useful as acute-acting therapeutics for the treatment of the insulin resistance of type 2 diabetes...
  50. pmc Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941
    Florence I Raynaud
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, UK
    Mol Cancer Ther 8:1725-38. 2009
    ..Together, these data support the development of GDC-0941 as a potent, orally bioavailable inhibitor of phosphatidylinositide 3-kinase. GDC-0941 has recently entered phase I clinical trials...
  51. ncbi Sorafenib induces apoptosis and autophagy in prostate cancer cells in vitro
    Anders Ullen
    Department of Oncology Pathology, Cancer Centrum Karolinska, Karolinska Institutet, 17176 Stockholm, Sweden
    Int J Oncol 37:15-20. 2010
    ....
  52. ncbi Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors
    Arati Sharma
    Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey 17033, USA
    Cancer Res 65:2412-21. 2005
    ..Thus, these studies identify the mechanistic underpinnings by which mutant (V599E)B-RAF promotes melanoma development and show the effectiveness of targeting this protein to inhibit melanoma tumor growth...
  53. ncbi Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: a Canadian payer perspective
    S V Sorensen
    United BioSource Corporation, Bethesda, Maryland, USA
    Thromb Haemost 105:908-19. 2011
    ..This study demonstrates that dabigatran etexilate is a highly cost-effective alternative to current care for the prevention of stroke and systemic embolism among Canadian AF patients...
  54. 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
    ....
  55. ncbi Sorafenib for the treatment of advanced renal cell carcinoma
    Robert C Kane
    Division of Drug Oncology Products, Center for Drug Evaluation and Research, U S Food and Drug Administration, Silver Spring, Maryland 20993 0004, USA
    Clin Cancer Res 12:7271-8. 2006
    ..S. Food and Drug Administration (FDA) review and approval of sorafenib (Nexavar, BAY43-9006), a new small-molecule, oral, multi-kinase inhibitor for the treatment of patients with advanced renal cell carcinoma (RCC)...
  56. ncbi Treatment modification in human immunodeficiency virus-infected individuals starting combination antiretroviral therapy between 2005 and 2008
    Luigia Elzi
    University Hospital Basel, Switzerland
    Arch Intern Med 170:57-65. 2010
    ..Adverse effects of combination antiretroviral therapy (CART) commonly result in treatment modification and poor adherence...
  57. 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...
  58. pmc Drugging the PI3 kinome: from chemical tools to drugs in the clinic
    Paul Workman
    Cancer Research UK Centre for Cancer Therapeutics, Section of Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, United Kingdom
    Cancer Res 70:2146-57. 2010
    ..The challenges and outlook for drugging the PI3 kinome are discussed in the more general context of the role of structural biology and chemical biology in innovative drug discovery...
  59. ncbi Randomized, placebo-controlled, phase III study of oxaliplatin, fluorouracil, and leucovorin with or without PTK787/ZK 222584 in patients with previously treated metastatic colorectal adenocarcinoma
    Eric Van Cutsem
    Digestive Oncology Unit, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium
    J Clin Oncol 29:2004-10. 2011
    ..PTK787/ZK 222584 (PTK/ZK) is a novel oral angiogenesis inhibitor with therapeutic potential for the treatment of solid tumors...
  60. pmc Blocking Hedgehog survival signaling at the level of the GLI genes induces DNA damage and extensive cell death in human colon carcinoma cells
    Tapati Mazumdar
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
    Cancer Res 71:5904-14. 2011
    ..Taken together, these findings establish that inhibition of HH signaling at the level of the GLI genes downstream of Smo is critical in the induction of DNA damage in early S-phase, leading to cell death in human colon carcinoma cells...
  61. ncbi An essential part for Rho-associated kinase in the transcellular invasion of tumor cells
    K Itoh
    Department of Tumor Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan
    Nat Med 5:221-5. 1999
    ..These results indicate that ROCK plays an essential part in tumor cell invasion, and demonstrate its potential as a therapeutic target for the prevention of cancer invasion and metastasis...
  62. ncbi Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma
    James G Christensen
    Department of Cancer Biology, Pfizer Global Research and Development, La Jolla Laboratories, 10724 Science Center Drive, La Jolla, CA 92121, USA
    Mol Cancer Ther 6:3314-22. 2007
    ..Collectively, these data illustrate the potential clinical utility of inhibitors of NPM-ALK in treatment of patients with ALK-positive ALCL...
  63. pmc Preferential binding of a G-quadruplex ligand to human chromosome ends
    Christine Granotier
    LRP, DRR, CEA 92265, Fontenay aux Roses, France
    Nucleic Acids Res 33:4182-90. 2005
    ..They support the hypothesis that G-quadruplex ligands induce and/or stabilize G-quadruplex structures at telomeres of human cells...
  64. ncbi Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial
    Hans Christoph Diener
    Department of Neurology, University Hospital Essen, Essen, Germany
    Lancet Neurol 9:1157-63. 2010
    ..We aimed to assess the effects of dabigatran compared with warfarin in the subgroup of patients with previous stroke or transient ischaemic attack...
  65. ncbi Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study
    Jean Michel Molina
    Department of Infectious Diseases, Hopital Saint Louis 1, Av C Vellefaux, 75475 Paris, Cedex 10, France
    J Acquir Immune Defic Syndr 53:323-32. 2010
    ..Once-daily atazanavir/ritonavir demonstrated similar antiviral efficacy to twice-daily lopinavir/ritonavir over 48 weeks, with less gastrointestinal disturbance and a better lipid profile, in treatment-naive patients...
  66. ncbi Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial
    R Loch MacDonald
    St Michael s Hospital, Division of Neurosurgery, Toronto, Ontario, Canada
    Stroke 39:3015-21. 2008
    ....
  67. pmc Transcriptional activation of the NF-kappaB p65 subunit by mitogen- and stress-activated protein kinase-1 (MSK1)
    Linda Vermeulen
    Department of Molecular Biology, University of Gent VIB, K L Ledeganckstraat 35, B 9000 Gent, Belgium
    EMBO J 22:1313-24. 2003
    ..This effect represents, together with phosphorylation of nucleosome components such as histone H3, an essential step leading to selective transcriptional activation of NF-kappaB-dependent gene expression...
  68. ncbi An autodissemination station for the transfer of an insect growth regulator to mosquito oviposition sites
    R Gaugler
    Center for Vector Biology, Rutgers University, 180 Jones Avenue, New Brunswick, NJ 08901 8536, U S A
    Med Vet Entomol 26:37-45. 2012
    ..Key autodissemination station features include lack of maintenance requirements, biodegradable construction, low cost and low risk...
  69. ncbi A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer
    K N Chi
    Department of Medical Oncology, Vancouver Centre, BC Cancer Agency, Vancouver, British Columbia
    Ann Oncol 19:746-51. 2008
    ..The purpose of this trial was to evaluate the antitumor activity of sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, in patients with castration-resistant prostate cancer...
  70. ncbi Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors
    Dirk Strumberg
    Department of Hematology and Medical Oncology, Marienhospital Herne, University Medical School of Bochum, Herne, Germany
    Oncologist 12:426-37. 2007
    ..Based on these findings, continuous daily 400 mg bid sorafenib was chosen as the optimal regimen for phase II/III studies. Trials are ongoing in renal cell carcinoma, hepatocellular carcinoma, melanoma, and non-small cell lung cancer...
  71. ncbi Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group
    David F McDermott
    Division of Hematology Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, East KS 159, Boston, MA, USA
    J Clin Oncol 26:2178-85. 2008
    ..This phase II study evaluated the efficacy and safety of sorafenib plus dacarbazine in patients with advanced melanoma...
  72. ncbi Cell cycle dependent and schedule-dependent antitumor effects of sorafenib combined with radiation
    John P Plastaras
    Laboratory of Molecular Oncology and Cell Cycle Regulation, Department of Medicine Hematology Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 67:9443-54. 2007
    ..This study establishes a foundation for clinical testing of sequential fractionated radiation followed by sorafenib in gastrointestinal and other malignancies...
  73. ncbi The role of Mcl-1 downregulation in the proapoptotic activity of the multikinase inhibitor BAY 43-9006
    Chunrong Yu
    Division of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Oncogene 24:6861-9. 2005
    ..Conversely, Mcl-1 downregulation by short hairpin RNA enhanced BAY 43-9006-induced apoptosis. Collectively, these findings demonstrate that drug-induced Mcl-1 downregulation contributes to the proapoptotic effects of BAY 43-9006...
  74. pmc RhoA is required for monocyte tail retraction during transendothelial migration
    R A Worthylake
    Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    J Cell Biol 154:147-60. 2001
    ..Finally, we find that p160ROCK signaling negatively regulates integrin adhesions and that inhibition of RhoA results in an accumulation of beta2 integrin in the unretracted tails...
  75. ncbi Laboratory and field comparisons of pyriproxyfen, polystyrene beads and other larvicidal methods against malaria vectors in Sri Lanka
    A M G M Yapabandara
    Regional Office, Anti Malaria Campaign, Matale, Sri Lanka
    Acta Trop 81:211-23. 2002
    ..However, the reduced required frequency for visiting every pit made the pyriproxyfen method the one of choice. The same low concentration of pyriproxyfen also effectively inhibited emergence of adults from river-bed pools...
  76. ncbi An orally available small-molecule inhibitor of c-Met, PF-2341066, exhibits cytoreductive antitumor efficacy through antiproliferative and antiangiogenic mechanisms
    Helen Y Zou
    Departments of Cancer Biology, Pfizer Global Research and Development, La Jolla Laboratories, La Jolla, California 92121, USA
    Cancer Res 67:4408-17. 2007
    ..Collectively, these results show the therapeutic potential of targeting c-Met with selective small-molecule inhibitors for the treatment of human cancers...
  77. ncbi Validation of an HPLC-UV method for sorafenib determination in human plasma and application to cancer patients in routine clinical practice
    B Blanchet
    Laboratoire de Pharmacologie Toxicologie, Service de Pharmacie, France
    J Pharm Biomed Anal 49:1109-14. 2009
    ..Finally, large interindividual variability and higher exposure in patients experiencing severe toxicity support the need for therapeutic drug monitoring to ensure an optimal exposure to sorafenib...
  78. ncbi Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents
    W P Spooren
    Novartis Pharma AG, Nervous System Research, Basel, Switzerland
    J Pharmacol Exp Ther 295:1267-75. 2000
    ..5 mg/kg) locomotor activity in mice and prepulse inhibition in rats (1, 3, or 10 mg/kg). Thus, these findings indicate that MPEP exhibits anxiolytic-like effects and low risks for sedation and psychotomimetic side-effects in rodents...
  79. ncbi A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma cells both in vitro and in vivo
    A Iwamaru
    Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 26:2435-44. 2007
    ..We conclude that WP1066 holds promise as a therapeutic agent against malignant gliomas...
  80. pmc The metabotropic glutamate receptor subtype 5 antagonist fenobam is analgesic and has improved in vivo selectivity compared with the prototypical antagonist 2-methyl-6-(phenylethynyl)-pyridine
    Michael C Montana
    Washington University Pain Center, Department of Anesthesiology, 660 S Euclid Ave, St Louis, MO 63110, USA
    J Pharmacol Exp Ther 330:834-43. 2009
    ..These results demonstrate that fenobam is analgesic in mice and has an improved in vivo selectivity for mGlu5 over MPEP...
  81. pmc Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts
    Karine Michaud
    Department of Neurological Surgery, Helen Diller Comprehensive Cancer Center, University of California San Francisco, California 94143 0520, USA
    Cancer Res 70:3228-38. 2010
    ..In total, our results support clinical trial evaluation of PD-0332991 against newly diagnosed as well as recurrent GBM, and indicate that Rb status is the primary determinant of potential benefit from this therapy...
  82. ncbi Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study)
    Michael D Ezekowitz
    Lankenau Institute for Medical Research and The Heart Center, Wynnewood, PA, USA
    Am J Cardiol 100:1419-26. 2007
    ..The 2 highest doses of dabigatran suppress D-dimer concentrations. Serious liver toxicity was not seen. The significance of the increase of DTB2 concentrations in dabigatran-treated patients needs resolution...
  83. pmc Sorafenib inhibits STAT3 activation to enhance TRAIL-mediated apoptosis in human pancreatic cancer cells
    Shengbing Huang
    Divisions of Oncology and Gastroenterology Hepatology, Mayo Cancer Center, Mayo Clinic, Rochester, Minnesota 55905, USA
    Mol Cancer Ther 9:742-50. 2010
    ..These data indicate that targeting STAT3 may enhance treatment efficacy against pancreatic cancer...
  84. pmc Hedgehog signaling drives cellular survival in human colon carcinoma cells
    Tapati Mazumdar
    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Cancer Res 71:1092-102. 2011
    ..Collectively, these results highlight the importance of Gli activation downstream of Smo as a therapeutic target in models of human colon carcinoma...
  85. pmc Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2
    Kevin J French
    Apogee Biotechnology Corporation, Hummelstown, PA 17036, USA
    J Pharmacol Exp Ther 333:129-39. 2010
    ..Therefore, this newly developed SK2 inhibitor provides an orally available drug candidate for the treatment of cancer and other diseases...
  86. ncbi Potential use of pyriproxyfen for control of Aedes aegypti (Diptera: Culicidae) in Iquitos, Perú
    Moises Sihuincha
    Laboratorio Referencial, Dirección de Salud, Iquitos, Peru
    J Med Entomol 42:620-30. 2005
    ..We review the literature on the environmental and human health effects of this compound and discuss its potential for use as a mosquito control agent in the field...
  87. ncbi BAY 43-9006 inhibition of oncogenic RET mutants
    Francesca Carlomagno
    Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita di Napoli Federico II, Naples, Italy
    J Natl Cancer Inst 98:326-34. 2006
    ..We evaluated whether the biaryl urea BAY 43-9006, which is known to inhibit several other tyrosine kinases, blocks RET kinase function and oncogenic activity...
  88. ncbi Safety and efficacy results of the advanced renal cell carcinoma sorafenib expanded access program in North America
    Walter M Stadler
    Department of Medicine, University of Chicago Medical Center, Chicago, Illinois
    Cancer 116:1272-80. 2010
    ..The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) program made sorafenib available to patients with advanced renal cell carcinoma (RCC) before regulatory approval...
  89. ncbi Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses
    Madeleine M Hipp
    Department of Hematology, Oncology and Immunology, University of Tubingen, Tubingen, Germany
    Blood 111:5610-20. 2008
    ..These results indicate that sunitinib, but not sorafenib, is suitable for combination with immunotherapeutic approaches for treatment of cancer patients...
  90. pmc Ras pathway activation in hepatocellular carcinoma and anti-tumoral effect of combined sorafenib and rapamycin in vivo
    Pippa Newell
    Mount Sinai Liver Cancer Program, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA
    J Hepatol 51:725-33. 2009
    ..We investigated the molecular alterations of the Ras pathway in HCC and the antineoplastic effects of sorafenib in combination with rapamycin, an inhibitor of mTOR pathway, in experimental models...
  91. pmc A clinical phase II study with sorafenib in patients with progressive hormone-refractory prostate cancer: a study of the CESAR Central European Society for Anticancer Drug Research-EWIV
    S Steinbild
    Tumor Biology Center, Albert Ludwigs University Freiburg Freiburg, Germany
    Br J Cancer 97:1480-5. 2007
    ..Sorafenib has antitumour activity in HRPCP when evaluated for RECIST- and PSA-based response. Further investigation as a component of combination regimens is necessary to evaluate its definite or overall clinical benefit for HRPCP...
  92. pmc Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study
    D Strumberg
    Department of Hematology and Medical Oncology, University of Bochum, Marienhospital Herne, Hölkeskampring 40, D 44625 Herne, Germany
    Br J Cancer 106:1722-7. 2012
    ..In a phase I dose-escalation study, regorafenib demonstrated tolerability and antitumour activity in solid tumour patients. The study was expanded to focus on patients with metastatic colorectal cancer (CRC)...
  93. ncbi A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients with advanced solid tumors
    Klaus Mross
    Tumour Biology Center, University Hospital, Freiburg, Germany
    Clin Cancer Res 18:2658-67. 2012
    ..This first-in-man, phase I dose-escalation study assessed the safety, pharmacokinetic, pharmacodynamic, and efficacy profiles of regorafenib in patients with advanced solid tumors...
  94. ncbi Dabigatran etexilate for stroke prevention in patients with atrial fibrillation: resolving uncertainties in routine practice
    Menno V Huisman
    Department of Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands
    Thromb Haemost 107:838-47. 2012
    ..In addition, cut-off values for different coagulation assay results associated with an increased risk of bleeding are given...
  95. pmc FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML
    Keith W Pratz
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21231, USA
    Blood 115:1425-32. 2010
    ..These results have important implications for the potential therapeutic use of FLT3 inhibitors in that patients with newly diagnosed FLT3-mutant AML might be less likely to respond clinically to highly selective FLT3 inhibition...
  96. ncbi Novel 1,2,4-triazolo[1,5-a]pyridines and their fused ring systems attenuate oxidative stress and prolong lifespan of Caenorhabiditis elegans
    Ramadan Ahmed Mekheimer
    Department of Chemistry, Faculty of Science for Girls, King Abdulaziz University, Jeddah, P O Box 50918, Jeddah 21533, Saudi Arabia
    J Med Chem 55:4169-77. 2012
    ..elegans in a dose-dependent manner. Furthermore, treatment of worms with compound 13 was found to significantly attenuate the formation of advanced glycation end products and malondialdehyde in a dose-dependent manner...
  97. pmc Allosteric drugs: the interaction of antitumor compound MKT-077 with human Hsp70 chaperones
    Aikaterini Rousaki
    Program in Biophysics, The University of Michigan, Ann Arbor, MI 48109, USA
    J Mol Biol 411:614-32. 2011
    ..Suggestions for the improvement of the compound's properties are made on the basis of the binding location and pose...
  98. ncbi Sorafenib induces cell death in chronic lymphocytic leukemia by translational downregulation of Mcl-1
    S Huber
    Third Department of Medicine, Technical University, Munich, Germany
    Leukemia 25:838-47. 2011
    ..Conclusively, sorafenib is highly active in CLL and may compose a new therapeutic option for patients who relapse after immunochemotherapy...
  99. ncbi Structure-based design of novel potent nonpeptide thrombin inhibitors
    Norbert H Hauel
    Boehringer Ingelheim Pharma KG, Research Division, Birkendorfer Strasse 65, D 88397 Biberach Riss, Germany
    J Med Chem 45:1757-66. 2002
    ..This zwitterionic molecule was converted into the double-prodrug 31 (BIBR 1048), which showed strong oral activity in different animal species. On the basis of these results, 31 was chosen for clinical development...
  100. ncbi Treatments for stroke prevention in atrial fibrillation: a network meta-analysis and indirect comparisons versus dabigatran etexilate
    Neil S Roskell
    Neil Roskell, RTI Health Solutions, Williams House, Manchester Science Park, Lloyd Street North, Manchester M15 6SE, UK
    Thromb Haemost 104:1106-15. 2010
    ..There was no indication of increased intracranial or extracranial haemorrhage with dabigatran etexilate compared to antiplatelet agents...
  101. ncbi A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: THE Randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN)
    Frans Van de Werf
    University Hospitals Leuven, Department of Cardiovascular Medicine, Leuven, Belgium
    Am Heart J 163:931-937.e1. 2012
    ..Vitamin K antagonists are the only oral anticoagulants approved for long-term treatment of patients with a cardiac valve replacement...

Research Grants62

  1. Pilot-Scale Heterocyclic and Carbocyclic Libraries for High Throughout Screening
    RICHARD LAROCK; Fiscal Year: 2009
    ..libraries of indoles, benzofurans, benzopyrans, coumarins, isocoumarins, phthalides, pyrones, 2-quinolones, pyridines, isoquinolin-1-ones, isoindolin-1-ones, isoquinolines, carbolines, isoindolo[2,1-a]indoles, carbazoles, ..
  2. Au/Pt Catalysis in the Synthesis of Elaborate N-Heterocycles: Methodology Develop
    Liming Zhang; Fiscal Year: 2013
    ..g., pyridines, pyrroles, oxazoles, pyrroline and indoles)...
  3. Synthesis of Medicinally Important Heterocycles
    RICHARD LAROCK; Fiscal Year: 2007
    ..benzopyrans, chromones and heteroatom analogues, furans, thiophenes, pyrroles, oxazoles, isoxazoles, pyrazoles, pyridines, quinolines, coumarins, indenes, indenones, naphthols, and phenols...
  4. Design, Syntheses and Studies of Novel Antituberculosis Agents
    Marvin J Miller; Fiscal Year: 2013
    ..synthesized, potent, non-toxic, remarkably selective small molecule antiTB agents, including imidazo[1,2-a]pyridines, the development of which will be the second goal...
  5. MOLECULAR MECHANISMS OF PRPP-SYNTHETASE OVERACTIVITY
    Blake Roessler; Fiscal Year: 1991
    ..formation of PRPP by this enzyme represents the first step in the de novo synthesis of purines, pyrimidines and pyridines. A considerable amount of information regarding this enzymes' physical and kinetic properties has been amassed...
  6. MOLECULAR MECHANISMS OF PRPP-SYNTHETASE OVERACTIVITY
    THOMAS PALELLA; Fiscal Year: 1990
    ..formation of PRPP by this enzyme represents the first step in the de novo synthesis of purines, pyrimidines and pyridines. A considerable amount of information regarding this enzymes' physical and kinetic properties has been amassed...
  7. DEVELOPING AN UNDERSTANDING OF ASYMMETRIC INDUCTION
    Patrick J Walsh; Fiscal Year: 2010
    ..to the synthesis of enantiomerically enriched heterocycles bearing important pharmacophores, such as furans and pyridines. We have also developed several new routes to pyranones, furanosidic aldehydes, furans, and pyrroles...
  8. Inhibitor of FtsZ Polymerization in M. tuberculosis
    Robert Reynolds; Fiscal Year: 2004
    ..The 2-alkoxy-carbonylamino-pyridines (2-ACPs) potently inhibit the growth of Mtb with an MIC99 (SRI-3072) as low as 0.15 microgram/ml (0...
  9. ONCOGENE DIRECTED SYNTHESIS OF CEPHALOSTATIN CANCER DRUG
    Philip Fuchs; Fiscal Year: 2004
    ..the contribution of the central arene moiety to anticancer activity by testing pairs of unsymmetrical annulated pyridines derived from the best simplified hexacyclic steroidal subunits...
  10. Synthesis of (-)-cananodine, an alkaloid active against hepatocellular carcinoma
    JAMES VYVYAN; Fiscal Year: 2007
    ..cross-coupling of alkenyl triflates, alkenyl boronates, or alkylzinc reagents with highly substituted pyridines having complementary functionality; 2) preparation of tetrahydro-5H-cyclohepta[b]pyridine derivatives via an ..
  11. Pyridine Synthesis via an Olefin C-H Alkenylation/Azaelectrocyclization Strategy
    ASHLEY BERMAN; Fiscal Year: 2009
    ..This strategy allows for the concise stereoselective synthesis of pyridines, providing rapid access to this important class of compounds from readily available starting materials...
  12. STUDIES IN ALKALOID TOTAL SYNTHESIS
    STEVEN WEINREB; Fiscal Year: 2003
    ..Finally, methodology for regioselective construction of highly substituted pyridines, which are components of the thiostreptone class of antibiotics, will be pursed via an intramolecular hetero ..
  13. ANTIRETROVIRAL THERAPIES AND SUBSTANCE ABUSE
    David Greenblatt; Fiscal Year: 2002
    ..The in vitro model, if validated, has the potential to provide clinically important information on interactions involving HIV treatments and abusable drugs, at relatively low cost and with no human drug exposure. ..
  14. CYP3A Function in Aging AfricanAmericans
    David Greenblatt; Fiscal Year: 2006
    ..This study should provide important mechanistic information on the role of age, gender, and ethnicity as sources of variability in CYP3A-mediated drug metabolism and response. ..
  15. MDR1 and Related Proteins during HIV PI Exposure
    David Greenblatt; Fiscal Year: 2005
    ..The findings will be of importance in understanding lipid disorders related to PIs as well as the kinetics of drugs used to treat HIV and related disorders. ..
  16. CHRONIC BENZODIAZEPINES: BEHAVIOR AND NEUROCHEMISTRY
    David Greenblatt; Fiscal Year: 2005
    ....
  17. GARLIC PREPARATIONS AND ANTIRETROVIRAL DRUGS
    David Greenblatt; Fiscal Year: 2004
    ..The work will provide immediately applicable clinical data on garlic interactions with antiretrovirals, as well as mechanistic data identifying the interaction process and its predictability from in vitro models. ..
  18. HAART Regimens in Substance Abusers
    David Greenblatt; Fiscal Year: 2003
    ....
  19. Metabolic Consequences of HAART: CYP3A and P-gp
    David Greenblatt; Fiscal Year: 2003
    ..This multidisciplinary proposal provides a clinical and scientific basis to assess the effects of currently available as well as experimental HAART medications on human CYP3A and P-gp. ..
  20. 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]..
  21. Synthesis of Macrolides, Steroids, Cyclopentanoids, etc.
    BARRY TROST; Fiscal Year: 2009
    ..These new synthetic methods apply to many structural types beyond those illustrated and constitutes a significant to gain access to complex molecular targets more easily. ..
  22. Adolescence: A Sensitive Period for Nicotine Addiction
    Edward Levin; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  23. Purchase of a 400 MHz Multi-Nuclear NMR Spectrometer
    JOSEPH RICE; Fiscal Year: 2008
    ..The availability of a high resolution multi-nuclear NMR spectrometer is an essential tool for determining the chemical structures of these compounds and advancing these research efforts. [unreadable] [unreadable] [unreadable]..
  24. 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. ..
  25. Cellular Targets for Gallium Compounds in Lymphoma
    Christopher Chitambar; Fiscal Year: 2008
    ..Our studies will provide new information regarding: a) the impact of HFE mutations on the response of lymphoma to gallium, and, b) the mechanism of action of gallium at the mitochondrial level. ..
  26. Locomotion Control by Lumbar Spinal Cord Stimulation
    Changfeng Tai; Fiscal Year: 2008
    ..The proposed studies will not only improve our understanding of locomotion control in lumbar spinal cord but also benefit SCI patients. ..
  27. MATERNAL HEALTH STATUS AND ADVERSE BIRTH OUTCOMES
    Jennifer Haas; Fiscal Year: 2002
    ..Such interventions should begin from the premise that improved maternal and infant outcomes can only come from improved maternal health. ..
  28. Structure/Function Studies on Flavoproteins
    Irina Sevrioukova; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  29. CLINICAL TRIALS OF FLAVOPIRIDOL WITH CHEMOTHERAPY
    Gary Schwartz; Fiscal Year: 2008
    ..Continue to examine the mechanisms by which flavopiridol potentiates CPT-11 induced apoptosis, which should provide the opportunity to identify new biomarkers of response for these flavopiridol drug combinations. ..
  30. The Functional Neuroanatomy of Acute Nicotinic Modulation of Impulsivity in Women
    Alexandra Potter; Fiscal Year: 2008
    ..This model may be useful for the examination of other drugs of abuse. [unreadable] [unreadable] [unreadable]..
  31. IMAGING DOPAMINE/SEROTONIN MECHANISMS IN COCAINE CRAVING
    DEAN WONG; Fiscal Year: 2003
    ..Testing of these hypotheses will provide novel and fundamental answers to craving mechanisms. ..
  32. Behavioral Genetics and Toxic Response
    Edward Levin; Fiscal Year: 2002
    ....
  33. CHILDRENS CANCER GROUP
    Katherine Matthay; Fiscal Year: 2002
    ..Our strong biology research laboratories in brain tumors, neuroblastoma and myeloproliferative disorders are conducting multiple biology studies in the Group and providing new information for future studies. ..
  34. Molecular Analysis and Role of RGS6 as a Novel Growth Suppressor
    Rory A Fisher; Fiscal Year: 2010
    ..This work will determine how RGS6 works and will determine the basis for loss of RGS6 expression in human cancers. These studies could contribute to novel approaches in cancer therapy. ..
  35. Interventions for Adherence to Oral Antipsychotic Medications in Schizophrenia
    DAWN IRENE VELLIGAN; Fiscal Year: 2010
    ..The public health implications include effective disease management, maximizing long-term outcomes, and containing health care costs for schizophrenia. ..
  36. Single Agents with Designed Combination Chemotherapy Potential
    Aleem Gangjee; Fiscal Year: 2010
    ..abstract_text> ..
  37. Calcium entry and vascular smooth muscle excitation
    KENNETH BYRON; Fiscal Year: 2006
    ..abstract_text> ..
  38. Novel, P. jirovecii Specific Antipneumocystis Agents
    Aleem Gangjee; Fiscal Year: 2009
    ..These agents could be used alone or in combination to treat PCP thus providing novel agents against a new target. ..
  39. Interferon gamma in autoimmune thyroiditis & thyroid function
    Patrizio Caturegli; Fiscal Year: 2007
    ..We also hypothesize that augmented TSH signaling is required to induce the adipocyte-rich phenotype, and cross thyr-IFNg transgenics to TSH receptor knockout mice. ..
  40. Role of Calcium in Cocaine-Induced Sensitization
    STEPHANIE LICATA; Fiscal Year: 2002
    ..Second, rats will receive either acute or repeated cocaine and relative abundance of either calmodulin or CaMKII will be measured in the VTA and substantia nigra using immunolabeling techniques. ..
  41. Computerized EMR-Assisted Smoking Cessation (CEASCE)
    Jennifer Haas; Fiscal Year: 2007
    ..Future Directions: Evaluate whether CEASCE can serve as a prototype for other common primary care problems that require counseling for behavior change. [unreadable] [unreadable]..
  42. Nicotinic-Antipsychotic Drug Interactions and Cognition
    Edward Levin; Fiscal Year: 2006
    ..abstract_text> ..
  43. Action of Novel Anti-tumor Agents on Cell Communication
    Diane Matesic; Fiscal Year: 2005
    ..abstract_text> ..
  44. 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. ..
  45. Third Generation Antiopportunistic Agents
    Aleem Gangjee; Fiscal Year: 2003
    ..Screening against tuberculosis (NIAID) and tumor cells in culture (NCI) is also proposed. ..
  46. MEDICATION ADHERENCE AND OUTCOMES IN SCHIZOPHRENIA
    Dawn Velligan; Fiscal Year: 2004
    ..Moreover, we hypothesize that compliance and functioning will return to baseline levels six months after discontinuation of treatment. ..
  47. OU Human Research Protection Program, Year 2
    Gary Raskob; Fiscal Year: 2003
    ..The University of Oklahoma is committed to maintaining these initiatives after the term of this award. ..
  48. 131 I-MIBG Escalating Dose Rapid Sequence Double Infusi*
    Katherine Matthay; Fiscal Year: 2004
    ..Significance: The higher tumor-specific radiation doses possible with this protocol may provide a treatment to improve response and survival in children with resistant neuroblastoma. ..
  49. Novel Antirivals for Hantavirus Pulmonary Syndrome
    JEFFREY ARTERBURN; Fiscal Year: 2003
    ..abstract_text> ..
  50. Cholinergic Effects on Inhibition and Delay in ADHD
    Alexandra Potter; Fiscal Year: 2005
    ..abstract_text> ..
  51. DAYTIME SLEEPINESS--PREVALENCE, CONSEQUENCES, AND RISKS
    Thomas Roth; Fiscal Year: 2003
    ..The important contribution of the present proposal is that it will be the first population-based study to use laboratory assessments, its consequences and risks to measure sleepiness. ..
  52. Mechanism of Ca2+ Sensitization in Smooth Muscle
    Toshio Kitazawa; Fiscal Year: 2006
    ..abstract_text> ..
  53. 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]..
  54. High End Computing for PET/SPECT
    DEAN WONG; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  55. Chemokine receptor CCR5 antagonists as novel anti-HIV agents
    Yan Zhang; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  56. Racial Segregation & Disparities in Cancer Outcomes
    Jennifer Haas; Fiscal Year: 2007
    ..The proposed study would provide empirical evidence that could give impetus to area-based interventions to reduce cancer disparities. ..
  57. Vanderbilt Mentored Clinical Research Scholar Program
    Nancy Brown; Fiscal Year: 2006
    ..The VCRS program will train successful new clinical investigators who will serve as leaders role in the post-genomic era. [unreadable] [unreadable] [unreadable]..
  58. Kim-1 in Renal Epithelial Cell Motility and Adhesion
    BENJAMIN HUMPHREYS; Fiscal Year: 2005
    ..The proposed studies will have great relevance in understanding the molecular mechanisms of renal regeneration and renal cell cancer invasion and metastasis. ..
  59. 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. ..
  60. SIGNALING BY VASOPRESSIN--ARTERIAL SMOOTH MUSCLE CELLS
    KENNETH BYRON; Fiscal Year: 2002
    ..Finally, the effects of AVP and other hormones on [Ca2+]i and membrane currents will be examined in freshly isolated smooth muscle cells from rat mesenteric arteries. ..
  61. A pharmacogenetic and pharmacodynamic study of erlotinib
    CHARLES RUDIN; Fiscal Year: 2004
    ..Defining the basis of this toxicity could also promote the development of EGFR-directed agents that may avoid such toxicity or that may be effective in a broader spectrum of cancer patients. ..