pyrazoles

Summary

Summary: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.

Top Publications

  1. pmc Role of AMP-activated protein kinase in mechanism of metformin action
    G Zhou
    Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Clin Invest 108:1167-74. 2001
  2. ncbi JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis
    Claire Harrison
    Guy s and St Thomas National Health Service Foundation Trust, Guy s Hospital, London, United Kingdom
    N Engl J Med 366:787-98. 2012
  3. pmc Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism
    Paul B Yu
    Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA
    Nat Chem Biol 4:33-41. 2008
  4. ncbi A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis
    Srdan Verstovsek
    Leukemia Department, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    N Engl J Med 366:799-807. 2012
  5. ncbi Apixaban 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 364:806-17. 2011
  6. ncbi Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis
    Srdan Verstovsek
    M D Anderson Cancer Center, Houston, TX 77030, USA
    N Engl J Med 363:1117-27. 2010
  7. pmc The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors
    Michael Hedvat
    Molecular Medicine, Beckman Research Institute, Irell and Manella Graduate School of Biological Sciences, City of Hope Cancer Center, Duarte, CA 91010, USA
    Cancer Cell 16:487-97. 2009
  8. pmc Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+ channel, IKCa1: a potential immunosuppressant
    H Wulff
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 97:8151-6. 2000
  9. pmc Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms
    Alfonso Quintas-Cardama
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 115:3109-17. 2010
  10. ncbi Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis
    Ralf Köhler
    Department of Nephrology, Benjamin Franklin Medical Center, Berlin, Germany
    Circulation 108:1119-25. 2003

Detail Information

Publications330 found, 100 shown here

  1. pmc Role of AMP-activated protein kinase in mechanism of metformin action
    G Zhou
    Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Clin Invest 108:1167-74. 2001
    ..Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders...
  2. ncbi JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis
    Claire Harrison
    Guy s and St Thomas National Health Service Foundation Trust, Guy s Hospital, London, United Kingdom
    N Engl J Med 366:787-98. 2012
    ..Treatment options for myelofibrosis are limited. We evaluated the efficacy and safety of ruxolitinib, a potent and selective Janus kinase (JAK) 1 and 2 inhibitor, as compared with the best available therapy, in patients with myelofibrosis...
  3. pmc Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism
    Paul B Yu
    Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA
    Nat Chem Biol 4:33-41. 2008
    ..These findings suggest an essential physiological role for hepatic BMP signaling in iron-hepcidin homeostasis...
  4. ncbi A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis
    Srdan Verstovsek
    Leukemia Department, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    N Engl J Med 366:799-807. 2012
    ..Ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2, has clinically significant activity in myelofibrosis...
  5. ncbi Apixaban 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 364:806-17. 2011
    ..Apixaban, a novel factor Xa inhibitor, may be an alternative treatment for such patients...
  6. ncbi Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis
    Srdan Verstovsek
    M D Anderson Cancer Center, Houston, TX 77030, USA
    N Engl J Med 363:1117-27. 2010
    ..INCB018424 is a potent and selective Janus kinase 1 (JAK1) and JAK2 inhibitor...
  7. pmc The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors
    Michael Hedvat
    Molecular Medicine, Beckman Research Institute, Irell and Manella Graduate School of Biological Sciences, City of Hope Cancer Center, Duarte, CA 91010, USA
    Cancer Cell 16:487-97. 2009
    ..We demonstrate the essential role of Stat3 downstream of Jaks by inhibition of tumor growth using short hairpin RNA targeting Stat3. Our data support a key role of Jak kinase activity in Stat3-dependent tumorigenesis...
  8. pmc Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+ channel, IKCa1: a potential immunosuppressant
    H Wulff
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 97:8151-6. 2000
    ..A series of pyrazoles, acetonitriles, and tetrazoles were synthesized and found to selectively block IKCa1...
  9. pmc Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms
    Alfonso Quintas-Cardama
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 115:3109-17. 2010
    ..Preliminary clinical results support these preclinical data and establish INCB018424 as a promising oral agent for the treatment of MPNs...
  10. ncbi Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis
    Ralf Köhler
    Department of Nephrology, Benjamin Franklin Medical Center, Berlin, Germany
    Circulation 108:1119-25. 2003
    ..In a rat model of balloon catheter injury (BCI), we investigated whether alterations in expression of Ca2+-activated K+ channels (KCa) contribute to intimal hyperplasia and vascular restenosis...
  11. pmc The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy
    Lee A Honigberg
    Pharmacyclics, Sunnyvale, CA 94085 4521, USA
    Proc Natl Acad Sci U S A 107:13075-80. 2010
    ..These findings support Btk inhibition as a therapeutic approach for the treatment of human diseases associated with activation of the BCR pathway...
  12. pmc Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765
    Sarah E M Herman
    Integrated Biomedical Science Graduate Program, The Ohio State University Medical Center, Columbus, OH, USA
    Blood 117:6287-96. 2011
    ..Based on these collective data, future efforts targeting BTK with the irreversible inhibitor PCI-32765 in clinical trials of CLL patients is warranted...
  13. ncbi Apixaban versus enoxaparin for thromboprophylaxis after hip replacement
    Michael Rud Lassen
    Department of Orthopedics, Spine Clinic, and Clinical Trial Unit, Hørsholm Hospital, University of Copenhagen, Hørsholm, Denmark
    N Engl J Med 363:2487-98. 2010
    ..Orally active, specific factor Xa inhibitors such as apixaban may provide effective thromboprophylaxis with a lower risk of bleeding and improved ease of use...
  14. ncbi Celecoxib for the prevention of colorectal adenomatous polyps
    Nadir Arber
    Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    N Engl J Med 355:885-95. 2006
    ..Overexpression of cyclooxygenase 2 (COX-2) has been associated with colorectal adenomatous polyps and cancer, prompting researchers to propose its inhibition as a chemopreventive intervention...
  15. pmc The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to atherogenesis in mice and humans
    Kazuyoshi Toyama
    Department of Medicine and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    J Clin Invest 118:3025-37. 2008
    ..These data suggest that KCa3.1 blockers represent a promising therapeutic strategy for atherosclerosis...
  16. pmc Considerations when measuring myocardial perfusion reserve by cardiovascular magnetic resonance using regadenoson
    Nicole M Bhave
    Departments of Medicine and Radiology, University of Chicago, Cardiac Imaging Center, Chicago, IL 60637, USA
    J Cardiovasc Magn Reson 14:89. 2012
    ..We sought to determine the optimal regadenoson CMR protocol for quantifying myocardial perfusion reserve index (MPRi) - more specifically, whether regadenoson stress imaging should be performed before or after rest imaging...
  17. ncbi Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): a randomised trial
    Francis K L Chan
    Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
    Lancet 376:173-9. 2010
    ..We aimed to compare risk of gastrointestinal events associated with celecoxib versus diclofenac slow release plus omeprazole...
  18. pmc Evaluation of the PBR/TSPO radioligand [(18)F]DPA-714 in a rat model of focal cerebral ischemia
    Abraham Martin
    INSERM U803, Orsay, France
    J Cereb Blood Flow Metab 30:230-41. 2010
    ..These results show that [(18)F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke...
  19. 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
    ....
  20. pmc Applications of small molecule BMP inhibitors in physiology and disease
    Charles C Hong
    Division of Cardiovascular Medicine and Center for Inherited Heart Disease, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, United States
    Cytokine Growth Factor Rev 20:409-18. 2009
    ..We also discuss several potential applications for small molecule BMP inhibitors, including stem cell manipulation, and the therapeutic modification of bone remodeling, heterotopic ossification, and iron homeostasis...
  21. ncbi A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding
    Raquel Gomez
    University Institute of Drug Dependencies, Department of Psychobiology, University Complutense of Madrid, Madrid 28223, Spain
    J Neurosci 22:9612-7. 2002
    ..Pretreatment with SR141716A enhanced the inhibition of feeding induced by intraperitoneal administration of oleoylethanolamide. The results reveal an unexpected role for peripheral CB1 receptors in the regulation of feeding...
  22. ncbi The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer
    P Venkatesan
    School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, India
    Biomaterials 32:3794-806. 2011
    ..The present study indicates a promising, effective and safe means of using celecoxib, and potentially other therapeutic agents for colon cancer therapy...
  23. ncbi PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer
    Patrizia Carpinelli
    Nerviano Medical Sciences S r l Oncology, Viale Pasteur 10, 20014 Nerviano, Milan, Italy
    Mol Cancer Ther 6:3158-68. 2007
    ..We conclude that PHA-739358, which is currently tested in clinical trials, has great therapeutic potential in anticancer therapy in a wide range of cancers...
  24. ncbi Apixaban or enoxaparin for thromboprophylaxis after knee replacement
    Michael Rud Lassen
    Department of Orthopedics, Spine Clinic, Clinical Trial Unit, Hørsholm Hospital, University of Copenhagen, Hørsholm, Denmark
    N Engl J Med 361:594-604. 2009
    ..Apixaban, a specific factor Xa inhibitor, may provide effective thromboprophylaxis with a low risk of bleeding and improved ease of use...
  25. pmc Blockade of T-lymphocyte KCa3.1 and Kv1.3 channels as novel immunosuppression strategy to prevent kidney allograft rejection
    I Grgic
    Department of Internal Medicine and Nephrology, University Hospital, Philipps University, Marburg, Germany
    Transplant Proc 41:2601-6. 2009
    ..Thus, selective blockade of T-lymphocyte K(Ca)3.1 and K(v)1.3 channels may represent a novel alternative therapy for prevention of kidney allograft rejection...
  26. pmc The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin
    Sonia A Tucci
    School of Psychology, University of Liverpool, Eleanor Rathbone Building, Bedford Street South, Liverpool L69 7ZA
    Br J Pharmacol 143:520-3. 2004
    ....
  27. ncbi Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo
    Kathleen M Leahy
    Pharmacia, Mail Zone AA4C, 700 Chesterfield Parkway, Chesterfield, Missouri 63017, USA
    Cancer Res 62:625-31. 2002
    ..2-3.0-fold) in response to celecoxib. Thus, the antitumor activity of celecoxib may be attributable, at least in part, to a direct effect on host stromal elements, such as the angiogenic vasculature...
  28. ncbi Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells
    A C Kreitzer
    Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
    Neuron 29:717-27. 2001
    ..DSE may provide a way for cells to use their firing rate to dynamically regulate synaptic inputs. Together with previous studies, these findings suggest a widespread role for endogenous cannabinoids in retrograde synaptic inhibition...
  29. ncbi Apixaban with antiplatelet therapy after acute coronary syndrome
    John H Alexander
    Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27715, USA
    N Engl J Med 365:699-708. 2011
    ..Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome...
  30. ncbi Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia
    Jean Pierre Despres
    Quebec Heart Institute, Laval Hospital Research Center, and the Division of Kinesiology, Department of Social and Preventive Medicine, Laval University, Ste Foy, Que, Canada
    N Engl J Med 353:2121-34. 2005
    ..The Rimonabant in Obesity-Lipids (RIO-Lipids) study examined the effects of rimonabant on metabolic risk factors, including adiponectin levels, in high-risk patients who are overweight or obese and have dyslipidemia...
  31. ncbi Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial
    Michael Rud Lassen
    Department of Orthopaedics, Spine Clinic, Clinical Trial Unit, Hørsholm Hospital, University of Copenhagen, Hørsholm, Denmark
    Lancet 375:807-15. 2010
    ..Apixaban, an orally active factor Xa inhibitor, might be as effective, have lower bleeding risk, and be easier to use than is enoxaparin. We assessed efficacy and safety of these drugs after elective total knee replacement...
  32. ncbi Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials
    Robin Christensen
    The Parker Institute, Musculoskeletal Statistics Unit, Frederiksberg Hospital, Frederiksberg, Denmark
    Lancet 370:1706-13. 2007
    ..We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant...
  33. ncbi Celecoxib: a review of its use for symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis
    Paul L McCormack
    Adis, a Wolters Kluwer Business, Auckland, New Zealand
    Drugs 71:2457-89. 2011
    ....
  34. ncbi Antagonists selective for estrogen receptor alpha
    Jun Sun
    Department of Molecular and Integrative Physiology, University of Illinois and University of Illinois College of Medicine, Urbana, Illinois 61801, USA
    Endocrinology 143:941-7. 2002
    ..In this way we have developed basic side-chain pyrazoles (BSC-pyrazoles) that are high affinity, potent, selective antagonists on ER(alpha)...
  35. pmc The effect of obesity on regadenoson-induced myocardial hyperemia: a quantitative magnetic resonance imaging study
    Edward V R DiBella
    UCAIR, Department of Radiology, University of Utah, Salt Lake City, UT, USA
    Int J Cardiovasc Imaging 28:1435-44. 2012
    ..Fixed dose regadenoson and weight adjusted adenosine produce similar measures of MPR in patients with a wide range of body sizes. Regadenoson is a potentially useful vasodilator for stress MRI studies...
  36. ncbi Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design
    Paul G Wyatt
    Astex Therapeutics Ltd, 436 Cambridge Science Park, Milton Road, Cambridge, CB4 0QA, United Kingdom
    J Med Chem 51:4986-99. 2008
    ..Optimisation of cellular activity and characterization of pharmacokinetic properties led to the identification of 33 (AT7519), which is currently being evaluated in clinical trials for the treatment of human cancers...
  37. pmc General Sensitization of melanoma cells for TRAIL-induced apoptosis by the potassium channel inhibitor TRAM-34 depends on release of SMAC
    Sandra Annika Quast
    Department of Dermatology and Allergy, Skin Cancer Center, University Medical Center Charite, Berlin, Germany
    PLoS ONE 7:e39290. 2012
    ..As both TRAIL and IK1 inhibitors had shown only minor side effects in clinical trials, a clinical application of this combination is conceivable...
  38. ncbi Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2
    Patricia McGettigan
    Discipline of Clinical Pharmacology, School of Medicine and Public Health, The University of Newcastle, New South Wales, Australia
    JAMA 296:1633-44. 2006
    ..Regulatory agencies have provided variable advice regarding the cardiovascular risks with older nonselective NSAIDs...
  39. pmc BMP4 promotes prostate tumor growth in bone through osteogenesis
    Yu Chen Lee
    Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, USA
    Cancer Res 71:5194-203. 2011
    ..Treatment of SCID mice bearing MDA-PCa-118b tumors with LDN-193189 significantly reduced tumor growth. Thus, these studies support a role of BMP4-mediated osteogenesis in the progression of prostate cancer in bone...
  40. pmc Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory
    Patrizia Campolongo
    Department of Physiology and Pharmacology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
    Proc Natl Acad Sci U S A 106:4888-93. 2009
    ..c.). These findings indicate that endocannabinoids in the BLA enhance memory consolidation and suggest that CB1 activity within this brain region is required for enabling glucocorticoid effects on memory consolidation enhancement...
  41. pmc Therapeutic potential of AZD1480 for the treatment of human glioblastoma
    Braden C McFarland
    Department of Cell Biology, 1918 University Blvd, MCLM 313, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Mol Cancer Ther 10:2384-93. 2011
    ....
  42. pmc Phase II, randomized, placebo-controlled trial of neoadjuvant celecoxib in men with clinically localized prostate cancer: evaluation of drug-specific biomarkers
    Emmanuel S Antonarakis
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA
    J Clin Oncol 27:4986-93. 2009
    ..We conducted a randomized, double-blind trial to examine the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at prostatectomy...
  43. ncbi Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial
    Ami E Iskandrian
    University of Alabama at Birmingham, Birmingham, AL 35294 0006, USA
    J Nucl Cardiol 14:645-58. 2007
    ..Earlier phase 1 and 2 studies have shown that regadenoson has desirable features as a stress agent for myocardial perfusion imaging...
  44. pmc In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors
    Jijun Hao
    Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    ACS Chem Biol 5:245-53. 2010
    ....
  45. ncbi Modulation of anxiety through blockade of anandamide hydrolysis
    Satish Kathuria
    Department of Pharmacology, University of California, Irvine, California, USA
    Nat Med 9:76-81. 2003
    ..Our results indicate that anandamide participates in the modulation of emotional states and point to fatty acid amide hydrolase inhibition as an innovative approach to anti-anxiety therapy...
  46. ncbi Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor xa inhibitors in development
    Bengt I Eriksson
    Orthopaedics Department, University Hospital Sahlgrenska Ostra, Gothenburg, Sweden
    Clin Pharmacokinet 48:1-22. 2009
    ..Here, we compare the pharmacokinetic and pharmacodynamic features of these new oral agents...
  47. ncbi Clinical and pharmacodynamic evaluation of metronomic cyclophosphamide, celecoxib, and dexamethasone in advanced hormone-refractory prostate cancer
    Andrea Fontana
    Division of Medical Oncology, Azienda USL 6 of Livorno, Italy
    Clin Cancer Res 15:4954-62. 2009
    ..v. standard dose of cyclophosphamide (CTX) immediately followed by an oral metronomic CTX regimen with celecoxib (CXB) and dexamethasone (DEX) in advanced hormone-refractory prostate cancer patients...
  48. ncbi Tachycardia caused by A2A adenosine receptor agonists is mediated by direct sympathoexcitation in awake rats
    Arvinder K Dhalla
    Department of Pharmacology, CV Therapeutics, Palo Alto, CA 94304, USA
    J Pharmacol Exp Ther 316:695-702. 2006
    ....
  49. ncbi Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening
    Timothy J Guzi
    Merck Research Laboratory, Cambridge, Masachusetts, USA
    Mol Cancer Ther 10:591-602. 2011
    ..SCH 900776 exposure phenocopies short interfering RNA-mediated CHK1 ablation and interacts synergistically with DNA antimetabolite agents in vitro and in vivo to selectively induce dsDNA breaks and cell death in tumor cell backgrounds...
  50. ncbi Phase II trial of celecoxib in prostate-specific antigen recurrent prostate cancer after definitive radiation therapy or radical prostatectomy
    Raj S Pruthi
    Division of Urologic Surgery, Department of Biostatistics, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    Clin Cancer Res 12:2172-7. 2006
    ..However, human trials are absent. This study evaluated the efficacy of the COX-2 inhibitor celecoxib in prostate-specific antigen (PSA) recurrent prostate cancer after radiation therapy (X-ray therapy or XRT) or radical prostatectomy...
  51. ncbi Endocannabinoid control of food intake and energy balance
    Vincenzo Di Marzo
    Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, 80078, Pozzuoli, Naples, Italy
    Nat Neurosci 8:585-9. 2005
    ..Here we discuss the multifaceted regulation of energy homeostasis by endocannabinoids, together with its applications to the treatment of eating disorders and metabolic syndromes...
  52. ncbi Maximal COX-2 immunostaining and clinical response to celecoxib and interferon alpha therapy in metastatic renal cell carcinoma
    Brian I Rini
    Department of Hematology and Oncology, Cleveland Clinic, Taussig Cancer Center, Cleveland, Ohio 44195, USA
    Cancer 106:566-75. 2006
    ..Based on potential additive or synergistic antitumor effects, interferon-alpha (IFNalpha) and celecoxib, an oral COX-2 inhibitor, were given to metastatic RCC patients in a Phase II trial...
  53. 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...
  54. pmc Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis
    Scott D Solomon
    Cardiovascular Division, Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115, USA
    Circulation 117:2104-13. 2008
    ..Our aim was to assess the cardiovascular risk associated with celecoxib in 3 dose regimens and to assess the relationship between baseline cardiovascular risk and effect of celecoxib on cardiovascular events...
  55. ncbi Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention
    Scott D Solomon
    Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    N Engl J Med 352:1071-80. 2005
    ..Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern...
  56. ncbi The novel NF-κB inhibitor DHMEQ synergizes with celecoxib to exert antitumor effects on human liver cancer cells by a ROS-dependent mechanism
    Nadia Lampiasi
    Institute of Biomedicine and Molecular Immunology Alberto Monroy, National Research Council, Palermo, Italy
    Cancer Lett 322:35-44. 2012
    ..These data suggest that the DHMEQ-CLX combination kills hepatoma cells via ROS production, ER stress response and the activation of intrinsic and extrinsic apoptotic pathways...
  57. ncbi Apixaban metabolism and pharmacokinetics after oral administration to humans
    Nirmala Raghavan
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Research and Development, Princeton, New Jersey 08543 4000, USA
    Drug Metab Dispos 37:74-81. 2009
    ..Thus, apixaban is an orally bioavailable inhibitor of factor Xa with elimination pathways that include metabolism and renal excretion...
  58. pmc The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers
    Takaaki Sasaki
    Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, D820, 44 Binney Street, Boston, MA 02115, USA
    Cancer Res 70:10038-43. 2010
    ..Our findings highlight the importance of studying drug resistance mechanisms in order to develop effective clinical treatments for patients with ALK-translocated cancers...
  59. ncbi Inhibition of the Ca²⁺-dependent K⁺ channel, KCNN4/KCa3.1, improves tissue protection and locomotor recovery after spinal cord injury
    Delphine Bouhy
    Centre for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, Quebec H3G1A4, Canada
    J Neurosci 31:16298-308. 2011
    ..These results suggest that blocking the KCa3.1 channel could be a potential therapeutic approach for treating secondary damage after spinal cord injury...
  60. ncbi Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay
    Yu Chen Barrett
    Bristol Myers Squibb, Princeton, New Jersey, USA
    Thromb Haemost 104:1263-71. 2010
    ..88-0.89) compared with PT/INR (r2 = 0.36) in patients undergoing VTE treatment suggested that anti-Xa activity was the better indicator of apixaban plasma concentrations...
  61. ncbi Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies
    P C Wong
    Thrombosis Research, Bristol Myers Squibb Company, Pennington, NJ 08534, USA
    J Thromb Haemost 6:820-9. 2008
    ..Apixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases...
  62. ncbi Efficacy and safety of the oral direct factor Xa inhibitor apixaban for symptomatic deep vein thrombosis. The Botticelli DVT dose-ranging study
    H Buller
    Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
    J Thromb Haemost 6:1313-8. 2008
    ..We conducted a dose-ranging study in patients with deep vein thrombosis...
  63. ncbi Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study
    H A Ghofrani
    Dept of Internal Medicine, Medical Clinic II V, University Hospital Giessen and Marburg GmbH, Klinikstrasse 36, 35392 Giessen, Germany
    Eur Respir J 36:792-9. 2010
    ..These preliminary data show that riociguat has a favourable safety profile and improves exercise capacity, symptoms and pulmonary haemodynamics in CTEPH and PAH. Randomised controlled trials are underway...
  64. ncbi NO-independent regulatory site on soluble guanylate cyclase
    J P Stasch
    Pharma Research Center, Bayer AG, Aprather Wey 18a, D 42096 Wuppertal, Germany
    Nature 410:212-5. 2001
    ..This results in antiplatelet activity, a strong decrease in blood pressure and an increase in survival in a low-NO rat model of hypertension, and as such may offer an approach for treating cardiovascular diseases...
  65. ncbi Comparative evaluation of the translocator protein radioligands 11C-DPA-713, 18F-DPA-714, and 11C-PK11195 in a rat model of acute neuroinflammation
    Fabien Chauveau
    CEA, DSV, I2BM, LIME, Orsay, France
    J Nucl Med 50:468-76. 2009
    ....
  66. ncbi PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity
    Chiara Soncini
    Nerviano Medical Sciences S r l Oncology, Milan, Italy
    Clin Cancer Res 12:4080-9. 2006
    ..The aim of this study was to determine the preclinical profile of a novel, highly selective Aurora kinase inhibitor, PHA-680632, as a candidate for anticancer therapy...
  67. pmc Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation
    Andrea U Steinbicker
    Department of Anesthesia, Harvard Medical School, Boston, MA, USA
    Blood 117:4915-23. 2011
    ..Our studies support the concept that BMP and IL-6 act together to regulate iron homeostasis and suggest that inhibition of BMP signaling may be an effective strategy for the treatment of anemia of inflammation...
  68. ncbi Cannabinoid receptor 1 (CB1) antagonism enhances glucose utilisation and activates brown adipose tissue in diet-induced obese mice
    M Bajzer
    Metabolic Diseases Institute, University of Cincinnati, 2140 East Galbraith Road, Building B, Room 332, Cincinnati, OH 45237 1625, USA
    Diabetologia 54:3121-31. 2011
    ....
  69. ncbi Preclinical pharmacokinetics and pharmacodynamics of apixaban, a potent and selective factor Xa inhibitor
    Kan He
    Pharmaceutical Candidate Optimization, Bristol Myers Squibb Company, Princeton, NJ, USA
    Eur J Drug Metab Pharmacokinet 36:129-39. 2011
    ..3 μM for dog. Apixaban exhibits desirable PK and PD properties for clinical development with good oral bioavailability, small Vd, low CL, and direct, predictable, concentration-dependent PD responses...
  70. pmc Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors
    Gregory D Cuny
    Laboratory for Drug Discovery in Neurodegeneration, Harvard NeuroDiscovery Center, Brigham and Women s Hospital and Harvard Medical School, 65 Landsdowne Street, Cambridge, MA 02139, USA
    Bioorg Med Chem Lett 18:4388-92. 2008
    ..g., plasma t(1/2)=1.6h) following intraperitoneal administration in mice. These studies provide useful molecular probes for examining the in vivo pharmacology of BMP signaling inhibition...
  71. ncbi Acute cannabinoid receptor type 1 (CB1R) modulation influences insulin sensitivity by an effect outside the central nervous system in mice
    D Song
    Department of Medicine, University of Toronto, Toronto, ON, Canada
    Diabetologia 54:1181-9. 2011
    ..Here we examined the relative contributions of acute CNS and extra-CNS CB1R modulation on insulin sensitivity using pharmacological gain- and loss-of-function of CB1R in mice...
  72. ncbi Reduced PBR/TSPO expression after minocycline treatment in a rat model of focal cerebral ischemia: a PET study using [(18)F]DPA-714
    Abraham Martin
    CEA, DSV, I BM, SHFJ, Laboratoire Imagerie Moléculaire Expérimentale, INSERM U803, 4 Place Géneral Leclerc, 91406 Orsay Cedex, France
    Mol Imaging Biol 13:10-5. 2011
    ..This overexpression can be imaged with positron emission tomography (PET) using PBR/TSPO-selective radioligands such as [(18)F]DPA-714...
  73. pmc Phase I and pharmacologic trial of cytosine arabinoside with the selective checkpoint 1 inhibitor Sch 900776 in refractory acute leukemias
    Judith E Karp
    Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Hospital, Baltimore, Maryland 21287, USA
    Clin Cancer Res 18:6723-31. 2012
    ..To extend these findings to the clinical setting, we have conducted a phase I study of cytarabine and SCH 900776...
  74. pmc Cannabinoid type-1 receptor reduces pain and neurotoxicity produced by chemotherapy
    Iryna A Khasabova
    Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota 55455, USA
    J Neurosci 32:7091-101. 2012
    ..Collectively, these results suggest that pharmacological facilitation of AEA signaling is a promising strategy for attenuating cisplatin-associated sensory neuropathy...
  75. ncbi COX-2 as a target for cancer chemotherapy
    Nilanjan Ghosh
    Dr B C Roy College of Pharmacy and Allied Health Sciences, Durgapur, India
    Pharmacol Rep 62:233-44. 2010
    ..Thus, it appears that targeting the COX-2 pathway is a promising strategy in the prevention and treatment of solid tumors...
  76. ncbi Effect of the AMP-kinase modulators AICAR, metformin and compound C on insulin secretion of INS-1E rat insulinoma cells under standard cell culture conditions
    Christian Langelueddecke
    Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria
    Cell Physiol Biochem 29:75-86. 2012
    ....
  77. pmc Preclinical development of the novel Chk1 inhibitor SCH900776 in combination with DNA-damaging agents and antimetabolites
    Ryan Montano
    Department of Pharmacology and Toxicology, Dartmouth Medical School, Lebanon, New Hampshire, USA
    Mol Cancer Ther 11:427-38. 2012
    ..Delayed administration of SCH900776 may be more effective than concurrent treatment. SCH900776 is currently in phase I clinical trials, and these results provide the rationale and schedule for future clinical trials...
  78. ncbi Synergistic effects of p38 mitogen-activated protein kinase inhibition with a corticosteroid in alveolar macrophages from patients with chronic obstructive pulmonary disease
    J Armstrong
    Medicines Evaluation Unit, National Institute for Health Research Translational Research Facility, University Hospital of South Manchester Foundation Trust, University of Manchester, Manchester, United Kingdom
    J Pharmacol Exp Ther 338:732-40. 2011
    ..Combining a p38 MAPK inhibitor with a corticosteroid synergistically enhances the anti-inflammatory effects on LPS-mediated cytokine production by alveolar macrophages from patients with COPD and controls...
  79. ncbi Death receptor regulation and celecoxib-induced apoptosis in human lung cancer cells
    Xiangguo Liu
    Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Natl Cancer Inst 96:1769-80. 2004
    ..We investigated the mechanism of celecoxib-induced apoptosis further...
  80. pmc Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial
    Susan O'Brien
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Electronic address
    Lancet Oncol 15:48-58. 2014
    ..We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia...
  81. pmc Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls
    Srdan Verstovsek
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Blood 120:1202-9. 2012
    ....
  82. pmc Compound C prevents the unfolded protein response during glucose deprivation through a mechanism independent of AMPK and BMP signaling
    Sakae Saito
    Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
    PLoS ONE 7:e45845. 2012
    ..Our findings demonstrate that compound C could be a unique tool for developing a UPR-targeted antitumor therapy...
  83. pmc Dual blockade of the EGFR and COX-2 pathways: a phase II trial of cetuximab and celecoxib in patients with chemotherapy refractory metastatic colorectal cancer
    Emily Chan
    Vanderbilt University Medical Center, Department of Veterans Affairs, Nashville, TN, USA
    Am J Clin Oncol 34:581-6. 2011
    ..This study explores the clinical and biological effects of combined blockade of these pathways...
  84. ncbi Peripheral endocannabinoid system-mediated actions of rimonabant on growth hormone secretion are ghrelin-dependent
    O Al-Massadi
    Instituto de Investigaciones Sanitarias, Complejo Hospitalario Universitario de Santiago de Compostela, SERGAS, Santiago de Compostela, Spain
    J Neuroendocrinol 22:1127-36. 2010
    ..In conclusion, the data reported in the present study establish, from a physiological point of view, the existence of a novel mechanism of GH regulation implicating the action of the cannabinoid receptor on the somatotroph axis...
  85. ncbi Cyclooxygenase-2 promotes hepatocellular carcinoma cell growth through Akt activation: evidence for Akt inhibition in celecoxib-induced apoptosis
    Jing Leng
    Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Hepatology 38:756-68. 2003
    ..01). In conclusion, our results suggest the involvement of COX-2-dependent and -independent mechanisms in celecoxib-mediated HCC cell apoptosis...
  86. ncbi Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study
    Gregory Cheng
    Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China
    Lancet 377:393-402. 2011
    ..We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period...
  87. ncbi MK1775, a selective Wee1 inhibitor, shows single-agent antitumor activity against sarcoma cells
    Jenny M Kreahling
    Experimental Therapeutics Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
    Mol Cancer Ther 11:174-82. 2012
    ..Finally, in patient-derived sarcoma samples, we showed that MK1775 as a single agent causes significant apoptotic cell death, suggesting that Wee1 inhibition may represent a novel approach in the treatment of sarcomas...
  88. pmc COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia
    M Farooqui
    1Division of Hematology, Oncology and Transplantation, the Vascular Biology Center, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA
    Br J Cancer 97:1523-31. 2007
    ..In fact, the combination provided significantly better analgesia than with morphine or celecoxib alone. Clinical trials of this combination for analgesia in chronic and severe pain in cancer are warranted...
  89. pmc Pharmacological suppression of hepcidin increases macrophage cholesterol efflux and reduces foam cell formation and atherosclerosis
    Omar Saeed
    Emory University Hospital Midtown, 550 Peachtree St NE, Atlanta, GA 30308, USA
    Arterioscler Thromb Vasc Biol 32:299-307. 2012
    ..In this study, we explored whether reducing macrophage intracellular iron levels via pharmacological suppression of hepcidin can increase macrophage-specific expression of cholesterol efflux transporters and reduce atherosclerosis...
  90. pmc Structure-activity relationships and X-ray structures describing the selectivity of aminopyrazole inhibitors for c-Jun N-terminal kinase 3 (JNK3) over p38
    Ted Kamenecka
    Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Jupiter, FL 33458, USA
    J Biol Chem 284:12853-61. 2009
    ....
  91. ncbi Rationale, design, and governance of Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION), a cardiovascular end point trial of nonsteroidal antiinflammatory agents in patients with arthritis
    Matthew C Becker
    Department of Cardiology, Cleveland Clinic Foundation, OH 44195, USA
    Am Heart J 157:606-12. 2009
    ..Pain management in patients with osteoarthritis or rheumatoid arthritis often requires long-term use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the relative cardiovascular safety of these therapies remains uncertain...
  92. pmc CH223191 is a ligand-selective antagonist of the Ah (Dioxin) receptor
    Bin Zhao
    Department of Environmental Toxicology, University of California, Davis, California 95616 8588, USA
    Toxicol Sci 117:393-403. 2010
    ....
  93. ncbi Targeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction
    Sih Min Tan
    Department of Medicine, St Vincent s Hospital, 29 Regent St, Fitzroy, Victoria 3065, Australia
    Am J Physiol Heart Circ Physiol 298:H1415-25. 2010
    ....
  94. pmc Identification and characterization of the first small molecule inhibitor of MDMX
    Damon Reed
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 285:10786-96. 2010
    ..When combined with selective MDM2 inhibitors, SJ-172550 may also be useful for treating tumors that express wild-type p53...
  95. pmc Receptors and channels targeted by synthetic cannabinoid receptor agonists and antagonists
    R G Pertwee
    Institute of Medical Sciences, University of Aberdeen, Foresterhill, Scotland, UK
    Curr Med Chem 17:1360-81. 2010
    ..It begins with a brief description of how each of these ligands interacts with CB(1) and/or CB(2) receptors...
  96. pmc Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis
    O Gallo
    Department of Oto Neuro Ophthalmologic Surgery, University of Florence, 50139 Florence, Italy
    Neoplasia 3:53-61. 2001
    ..This study suggests a central role of COX-2 pathway in HNC angiogenesis by modulating VEGF production and indicates that COX-2 inhibitors may be useful in HNC treatment...
  97. ncbi QSAR analysis for some diaryl-substituted pyrazoles as CCR2 inhibitors by GA-stepwise MLR
    Lotfollah Saghaie
    Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
    Chem Biol Drug Des 77:75-85. 2011
    Quantitative relationships between calculated molecular structure and 26 diaryl-substituted pyrazoles CCR2 inhibitors were investigated by GA-stepwise multiple linear regression...
  98. ncbi Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia
    Giovanni Mantovani
    Department of Medical Oncology, University of Cagliari, Cagliari, Italy
    J Mol Med (Berl) 88:85-92. 2010
    ..Therefore, phase III clinical trials are warranted to test the efficacy and safety of celecoxib...
  99. ncbi A small-molecule modulator interacts directly with deltaPhe508-CFTR to modify its ATPase activity and conformational stability
    Leigh Wellhauser
    Research Institute, Hospital for Sick Children and Departments of Biochemistry and Physiology, University of Toronto, Canada
    Mol Pharmacol 75:1430-8. 2009
    ..These findings suggest that direct binding of this small molecule induces and/or stabilizes a structure that promotes the channel open state and may underlie its efficacy as a corrector of DeltaPhe508-CFTR...
  100. pmc Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor
    James E Butrynski
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    N Engl J Med 363:1727-33. 2010
    ..Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.)...
  101. pmc Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK
    Ryohei Katayama
    Massachusetts General Hospital Cancer Center, Boston, MA 02129, USA
    Proc Natl Acad Sci U S A 108:7535-40. 2011
    ..Thus, we have developed a model of acquired resistance to ALK inhibitors and have shown that second-generation ALK TKIs or Hsp90 inhibitors are effective in treating crizotinib-resistant tumors harboring secondary gatekeeper mutations...

Research Grants75

  1. 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...
  2. Phase II Environmentally greener, efficient, and safe synthetic platform for the
    PAUL MATTHEW HERRINTON; Fiscal Year: 2011
    ..portfolio of borylated pyridine derivatives and add quinolines, pyrazines, pyrimidines, diazenes, imidazoles, pyrazoles, oxazoles, etc. Produce oxidized products (e.g. hydroxyquinolines) where applicable. 2...
  3. Molecular Pathways Targeted by Potent Antimalarial Pyrazole Compounds
    Akhil B Vaidya; Fiscal Year: 2013
    ..Recent studies suggest that pyrazoles and another series of potent antimalarials, spiroindolones, may be working through a common pathway...
  4. NMR/COMPUTER MODELING FOR CANNABINOID LIGAND DESIGN
    Xiang Qun Xie; Fiscal Year: 2002
    ..to three known cannabimimetic groups, namely arachidonylethanolamides (AEAs), aminoalkylindoles (AAIs), and pyrazoles (PRZs) will be studied using NMR methods and then refined using computer modeling approaches...
  5. Apoptosis in myelofibrosis with myeloid metaplasia
    Ruben Mesa; Fiscal Year: 2006
    ..abstract_text> ..
  6. Developmental Psychopharmacology of Antipsychotics
    JENNY WILEY; Fiscal Year: 2007
    ..This information will help to provide a more rational basis for making treatment decisions concerning children and adolescents who may benefit from treatment with an antipsychotic. [unreadable] [unreadable]..
  7. CB1 Receptors: Cocaine Reinforcement and Relapse
    Sara Ward; Fiscal Year: 2007
    ..The second goal is to employ this set of procedures to assess the role of the CB1 receptor system in cocaine's reinforcing effects and relapse to cocaine seeking. ..
  8. Proteomics and Biomarkers for Hepatocellular Cancer
    Nezam Afdhal; Fiscal Year: 2004
    ..These studies may lead to identification of more specific and sensitive biomarkers for HCC in HCV which can then be validated further in prospective clinical trials. ..
  9. Antiviral Therapy in African Americans with HCV
    Nezam Afdhal; Fiscal Year: 2005
    ..Specimens of liver tissue and serum will be collected for basic studies on viral resistance. These studies should help determine the best therapy for AA with HCV. ..
  10. "Post-partum steroid withdrawal-induced depression"
    REBECCA CRAFT; Fiscal Year: 2006
    ..Findings from the proposed model will enhance our understanding of the etiology of PPD and possibly lead to improved treatment options. ..
  11. Improving Contraceptive Effectiveness in Obese Women
    Alison B Edelman; Fiscal Year: 2010
    ..abstract_text> ..
  12. PROTEIN LIPID INTERACTIONS IN GALLSTONE PATHOGENESIS
    Nezam Afdhal; Fiscal Year: 2002
    ..These studies may lead to strategies for the prevention and non-surgical therapy of this very common disease. ..
  13. Drug discrimination and THC withdrawal in monkeys
    LANCE MCMAHON; Fiscal Year: 2005
    ..abstract_text> ..
  14. Pharmacotherapy of Cannabinoid Withdrawal: Pre-Clinical Studies
    Lance R McMahon; Fiscal Year: 2010
    ..Collectively, these specific aims provide a framework for developing novel pharmacotherapies of marijuana withdrawal that could markedly decrease marijuana use and dependence. ..
  15. Contraceptive efficacy and body weight: Does obesity affect the risk of failure?
    Alison Edelman; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  16. Breast Cancer Prediction Using Nipple Aspirate Fluid
    Edward Sauter; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  17. Protein Profiling in Nipple Aspirate Fluid
    Edward Sauter; Fiscal Year: 2007
    ..abstract_text> ..
  18. REGULATION OF SECRETION FROM HUMAN BASOPHILS
    Donald MacGlashan; Fiscal Year: 2009
    ..A population of subjects will be examined for this relationship. ..
  19. The Effect of Black Cohosh Extract on the Human Breast
    Edward Sauter; Fiscal Year: 2004
    ..The findings should allow us to design a high quality R01 submission involving a larger, randomized study of longer duration which should provide some answers on the potential role of BCE in breast cancer. ..
  20. HYPOXIC STRESS MECHANISMS IN RADIATION AND CHEMOTHERAPY
    Keith Laderoute; Fiscal Year: 2009
    ..An understanding of these MTF-1-dependent properties should aid in the development of novel prognostic and new modalities for neoplastic diseases. ..
  21. NABTC - M.D. Anderson Clinical Center
    Mark Gilbert; Fiscal Year: 2008
    ..The NABTC continues with the long-term goal of developing more effective treatments for patients with primary brain tumors, particularly malignant gliomas, combining longevity with the quality of survival. ..
  22. Sex Differences in Endocannabioid-Mediated Behaviors
    Christian Reich; Fiscal Year: 2008
    ..Fear conditioning will be performed with established classical-conditioning protocols. [unreadable] [unreadable]..
  23. Strengthening Botanical CAM Research: A Collaboration between CUNY and Columbia
    Edward Kennelly; Fiscal Year: 2007
    ..We anticipate that within a year after the end of the project period, several R21 or R01 botanically-related CAM applications will be submitted to NIH. ..
  24. Symposium on Aldo-Keto Reductases & Toxicant Metabolism
    TREVOR PENNING; Fiscal Year: 2002
    ..abstract_text> ..
  25. DRUGS AND DEVELOPMENT OF THE ADRENERGIC NERVOUS SYSTEM
    Theodore Slotkin; Fiscal Year: 2003
    ....
  26. DNA and Phytochemical Fingerprinting of Actaea Species
    Edward Kennelly; Fiscal Year: 2007
    ..Our long-range goals are to improve the quality of black cohosh dietary supplements and understand the variation in Actaea species. ..
  27. Cell Survival Pathways and Inhibitors in Leukemia
    Alan Eastman; Fiscal Year: 2003
    ....
  28. The Role of Adenosine in Chronic Ischemic Cardiomyopathy
    DAI TRANG LE; Fiscal Year: 2007
    ..Joel Linden who is an authority on the role of adenosine in cardiovascular physiology and pharmacology. ..
  29. Periodontal Assessment in RA Study (PARAS)
    Clifton Bingham; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  30. Reproductive Consequences of Pubertal Morphine Abuse
    Elizabeth Byrnes; Fiscal Year: 2002
    ....
  31. Prenatal Cannabis Effect on the Endocannabinoid System
    VINOD YARAGUDRI; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  32. Predictive Markers of Glioblastoma Response to VEGF Trap
    John de Groot; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  33. 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. ..
  34. PHASE I TRIALS OF ANTICANCER AGENTS
    Martin Edelman; Fiscal Year: 2002
    ....
  35. DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS
    Arun K Ghosh; Fiscal Year: 2010
    ..This research integrates organic synthesis, protein-ligand x-ray crystallography, molecular modeling and in-depth virus and cell-biological studies to design the next generation of HIV-1 protease inhibitors. ..
  36. BEHAVIORAL TOXICITY OF MDMA IN RHESUS MONKEYS
    MICHAEL TAFFE; Fiscal Year: 2009
    ..Specific Aim IV: To determine if a history of MDMA exposure impairs acquisition and performance of a battery of neuropsychological tests. ..
  37. NEUROPHARMACOLOGY OF PRIMATE COGNITION
    MICHAEL TAFFE; Fiscal Year: 2002
    ..abstract_text> ..
  38. Semiparametric ROC Curve Regression for Cancer Screening Studies
    Xiaofei Wang; Fiscal Year: 2008
    ..With a growing interest in rigorous validation of screening tests for cancer and other diseases, the proposed methods may end broad usage. [unreadable] [unreadable] [unreadable]..
  39. AhR and reproductive aging
    BRIAN PETROFF; Fiscal Year: 2008
    ..This project will provide crucial knowledge for the identification and prevention of infertility and birth defects due to the AhR pathway in older mothers. [unreadable] [unreadable] [unreadable]..
  40. TOXICOLOGY OF ENVIRONMENT CONTAMINANTS
    Stephen Safe; Fiscal Year: 2007
    ..The proposed training program will continue to provide trainees with a challenging academic and research environment that will prepare them for future careers in academic, industry and government. ..
  41. Inhibition of Pancreatic Cancer by New PPARgamma Agonis*
    Stephen Safe; Fiscal Year: 2008
    ..PPAR? -active C-substituted DIMs that inhibit pancreatic cancer cell growth in vitro and in vivo, and these will serve as lead compounds for development of new drugs for clinical treatment of this devastating disease ..
  42. Serine-Protease Effects on the Epithelial Sodium Channel
    Ray Caldwell; Fiscal Year: 2006
    ..Collectively, these components will be vital for him to emerge as an independent investigator [unreadable] [unreadable]..
  43. Regulation of Mammalian Oocyte Maturation
    Stephen Downs; Fiscal Year: 2007
    ..Furthermore, these studies will benefit the development of in vitro systems where either meiotic arrest or completion of meiotic maturation is the desired endpoint. ..
  44. Phase I Trial of Safingol and Cisplatin
    Gary Schwartz; Fiscal Year: 2006
    ..conduct "proof of principle" biological assays to measure the degree of ceramide production and/or S1P inhibition, either of which may be predictive of clinical outcome or toxicity. ..
  45. MECHANISMS OF CHLORPYRIFOS DEVELOPMENTAL NEUROTOXICITY
    Theodore Slotkin; Fiscal Year: 2004
    ..Molecular mechanisms of developmental neurotoxicity can be determined and linked to eventual alterations in behavioral performance. ..
  46. Coactivation of Estrogen Receptor alpha/Sp1
    Stephen Safe; Fiscal Year: 2006
    ..abstract_text> ..
  47. Identification of Alcohol Binding Site(s) in Protein Kinase C Epsilon
    Joydip Das; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  48. FORMAL METHODS APPLIED TO BIOLOGICAL SIGNALING NETWORKS
    Keith Laderoute; Fiscal Year: 2006
    ..abstract_text> ..
  49. Calcium entry and vascular smooth muscle excitation
    KENNETH BYRON; Fiscal Year: 2006
    ..abstract_text> ..
  50. ETHANOL EFFECTS ON BONE FORMATION IN PREGNANCY
    Martin Ronis; Fiscal Year: 2006
    ..The role of CYP2E1 and free radicals in the skeletal toxicity of ethanol during these periods will also be studied. ..
  51. OU Developmental Center for Injury Prevention Research
    Gary Raskob; Fiscal Year: 2005
    ..abstract_text> ..
  52. EVALUATION OF THE NA+ CHANNEL OUTER VESTIBULE
    SAMUEL DUDLEY; Fiscal Year: 2004
    ..Multiple toxins will used to probe as much of the outer vestibule as possible, to serve as validation of results obtain with other ligands, and to develop sufficient interaction points to constrain adequately the model. ..
  53. Hu1D10 in CLL: CLINICAL AND LABORATORY STUDIES
    John Byrd; Fiscal Year: 2006
    ..abstract_text> ..
  54. Fetal & Adolescent Nicotine Effects on CNS 5HT Systems
    Theodore Slotkin; Fiscal Year: 2003
    ..abstract_text> ..
  55. CELL DEATH INDUCED BY ANTICANCER AGENTS
    Alan Eastman; Fiscal Year: 2007
    ..The ultimate goal of this research program will be to define which pathway and effector a specific leukemia uses, and then prescribe effective drug combinations that will be individualized for that patient. ..
  56. MENTORING FOR NEW CANCER THERAPEAUTICS
    Gary Schwartz; Fiscal Year: 2005
    ..This K24 award mechanism represents the essence of what we are proposing and for which support is needed. ..
  57. SIV Behavioral Pathology: Manipulation of Viral Load
    MICHAEL TAFFE; Fiscal Year: 2004
    ..abstract_text> ..
  58. Transporter maintenance of dopamine homeostasis
    CLARE WILHELM; Fiscal Year: 2005
    ....
  59. Pharmacoresistance in rats with kainate-induced epilepsy
    F Dudek; Fiscal Year: 2005
    ..abstract_text> ..
  60. IMAGING DOPAMINE RELEASE/ENDOCRINE CHANGES IN ALCOHOLISM
    DEAN WONG; Fiscal Year: 2004
    ..If the initial D2 receptor deficits are exacerbated by alcohol abuse one can envision a positive feedback loop hard to break. ..
  61. Dedicated High Performance Human Brain/Preclinical PET
    DEAN WONG; Fiscal Year: 2004
    ..abstract_text> ..
  62. LOCAL INTERACTIONS BETWEEN HIPPOCAMPAL NEURONS
    F Edward Dudek; Fiscal Year: 2006
    ....
  63. High End Computing for PET/SPECT
    DEAN WONG; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  64. 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. ..
  65. Gene Expression in Prediabetes: Potential Role of PGC-1
    MARY PATTI; Fiscal Year: 2006
    ..abstract_text> ..
  66. MECHANISMS OF DOPAMINE & SEROTONIN IN TOURETTE SYNDROME
    DEAN WONG; Fiscal Year: 2003
    ..We propose to carry out experiments using PET to establish a more complete understanding of the neurotransmission in TS. This will also help establish new ationales for improved therapeutics in TS. ..
  67. Progression of temporal lobe epilepsy
    F Edward Dudek; Fiscal Year: 2007
    ..abstract_text> ..
  68. Fluorescent Zinc Sensors for Cellular Imaging
    CHRISTOPH FAHRNI; Fiscal Year: 2008
    ..The lack of a non-invasive zinc specific fluorescent sensor is currently a limiting factor in the study of intracellular zinc regulation and trafficking. ..
  69. ETHANOL METABOLISM IN PREGNANCY--ROLE OF DIET
    Martin Ronis; Fiscal Year: 2005
    ....
  70. Lipitor/Celebrex: effect on prostate cancer progression
    Xi Zheng; Fiscal Year: 2007
    ..This combination of drugs may significantly improve the management of prostate cancer. [unreadable] [unreadable] [unreadable]..
  71. Role of inositol trisphosphate in preconditioning
    Karin Przyklenk; Fiscal Year: 2004
    ....
  72. Aging, Adenosine and Platelet-Mediated Thrombosis
    Karin Przyklenk; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  73. DOMINANT NEGATIVE ESTROGEN RECEPTORS AND BREAST CANCER
    Benita Katzenellenbogen; Fiscal Year: 2002
    ..I. will introduce the gene- selective DN-ERs into cells using her efficient adenovirus system, determine their effects on gene expression, and examine their importance in ER regulated breast cancer cell proliferation and invasiveness. ..
  74. Preconditioning Improves Coronary Patency
    Karin Przyklenk; Fiscal Year: 2007
    ..The resulting mechanistic insights may, ultimately, be exploited in the future design of novel therapies for the clinical treatment of recurrent thrombosis. ..