indazoles

Summary

Top Publications

  1. ncbi Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results
    Hope S Rugo
    University of California, San Francisco Comprehensive Cancer Center, USA
    J Clin Oncol 23:5474-83. 2005
  2. ncbi Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study
    Ezra E W Cohen
    Section of Hematology Oncology, Department of Medicine, University of Chicago Division of Biological Sciences, 5801 S Ellis, Chicago, IL 60637, USA
    J Clin Oncol 26:4708-13. 2008
  3. ncbi The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer
    Adrian J Folkes
    Piramed Pharma, 957 Buckingham Avenue, Slough, Berks SL1 4NL, United Kingdom
    J Med Chem 51:5522-32. 2008
  4. 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
  5. ncbi Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3
    Dana D Hu-Lowe
    Department of Cancer Biology, PGRD La Jolla, Pfizer, Inc, San Diego, California 92121, USA
    Clin Cancer Res 14:7272-83. 2008
  6. ncbi Effect of axitinib (AG-013736) on fatigue, thyroid-stimulating hormone, and biomarkers: a phase I study in Japanese patients
    Toru Mukohara
    National Cancer Center Hospital East, Oncology Hematology, Kashiwa, Japan
    Cancer Sci 101:963-8. 2010
  7. 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
  8. pmc Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure
    Nizar M Tannir
    University of Texas, MD Anderson Cancer Center, Houston, 77030, USA
    Eur J Cancer 47:2706-14. 2011
  9. ncbi Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39
    Dexin Kong
    Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3 10 6, Ariake, Koto ku, Tokyo 135 8550, Japan
    Eur J Cancer 46:1111-21. 2010
  10. ncbi Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition
    E K H Han
    Abbott Laboratories, Global Pharmaceutical Research Division, Cancer Research, IL 60064, USA
    Oncogene 26:5655-61. 2007

Detail Information

Publications261 found, 100 shown here

  1. ncbi Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results
    Hope S Rugo
    University of California, San Francisco Comprehensive Cancer Center, USA
    J Clin Oncol 23:5474-83. 2005
    ....
  2. ncbi Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study
    Ezra E W Cohen
    Section of Hematology Oncology, Department of Medicine, University of Chicago Division of Biological Sciences, 5801 S Ellis, Chicago, IL 60637, USA
    J Clin Oncol 26:4708-13. 2008
    ..This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer...
  3. ncbi The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer
    Adrian J Folkes
    Piramed Pharma, 957 Buckingham Avenue, Slough, Berks SL1 4NL, United Kingdom
    J Med Chem 51:5522-32. 2008
    ..This work resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer...
  4. 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
    ....
  5. ncbi Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3
    Dana D Hu-Lowe
    Department of Cancer Biology, PGRD La Jolla, Pfizer, Inc, San Diego, California 92121, USA
    Clin Cancer Res 14:7272-83. 2008
    ..We provide a comprehensive description of its in vitro characteristics and activities, in vivo antiangiogenesis, and antitumor efficacy and translational pharmacology data...
  6. ncbi Effect of axitinib (AG-013736) on fatigue, thyroid-stimulating hormone, and biomarkers: a phase I study in Japanese patients
    Toru Mukohara
    National Cancer Center Hospital East, Oncology Hematology, Kashiwa, Japan
    Cancer Sci 101:963-8. 2010
    ..Axitinib 5 mg twice-daily is the recommended starting dose for Japanese patients. This trial is registered with ClinicalTrials.gov, identifier NCT00447005...
  7. 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...
  8. pmc Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure
    Nizar M Tannir
    University of Texas, MD Anderson Cancer Center, Houston, 77030, USA
    Eur J Cancer 47:2706-14. 2011
    ..This study assessed the efficacy and safety of linifanib in patients with advanced renal cell carcinoma (RCC) who were previously treated with sunitinib...
  9. ncbi Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39
    Dexin Kong
    Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3 10 6, Ariake, Koto ku, Tokyo 135 8550, Japan
    Eur J Cancer 46:1111-21. 2010
    ..The biological implication of the difference in molecular target specificity of these PI3K inhibitors is under investigation...
  10. ncbi Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition
    E K H Han
    Abbott Laboratories, Global Pharmaceutical Research Division, Cancer Research, IL 60064, USA
    Oncogene 26:5655-61. 2007
    ....
  11. ncbi Anticancer mechanisms of YC-1 in human lung cancer cell line, NCI-H226
    Chun Jen Chen
    Graduate Institute of Pharmaceutical Chemistry, China Medical University, No 91, Hsueh Shih Road, Taichung 40421, Taiwan, ROC
    Biochem Pharmacol 75:360-8. 2008
    ..These findings suggest a mechanism of cytotoxic action of YC-1 and indicate that YC-1 may be a promising chemotherapy agent against lung cancer...
  12. pmc Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients
    Yutaka Fujiwara
    Medical Oncology Hematology, Department of Medicine, Kobe University Hospital, 7 5 2, Kusunoki cho, Chuo Ku, Kobe, 650 0017, Japan
    Invest New Drugs 30:1055-64. 2012
    ..We report on data obtained from 18 Japanese patients with advanced solid tumors in two phase I trials that evaluated the safety, pharmacokinetics and antitumor activity of axitinib and also examined potential biomarkers...
  13. ncbi Key predictive factors of axitinib (AG-013736)-induced proteinuria and efficacy: a phase II study in Japanese patients with cytokine-refractory metastatic renal cell Carcinoma
    Yoshihiko Tomita
    Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Japan
    Eur J Cancer 47:2592-602. 2011
    ..This phase II study investigated axitinib efficacy, safety and biomarkers in Japanese patients with cytokine-refractory metastatic renal cell carcinoma (mRCC)...
  14. ncbi Guanylate cyclase activator YC-1 potentiates apoptotic effect of licochalcone A on human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathways
    Chung Soo Lee
    Department of Pharmacology, College of Medicine, Chung Ang University, Seoul 156 756, South Korea
    Eur J Pharmacol 683:54-62. 2012
    ..The combination of licochalcone A and YC-1 may confer a benefit in the treatment of human epithelial ovarian adenocarcinoma...
  15. pmc Intracellular protein binding patterns of the anticancer ruthenium drugs KP1019 and KP1339
    Petra Heffeter
    Department of Medicine I, Institute of Cancer Research, Medical University Vienna, Austria
    J Biol Inorg Chem 15:737-48. 2010
    ..The different protein binding patterns as compared with those for cisplatin suggest specific protein targets and consequently a unique mode of action for the ruthenium drugs investigated...
  16. ncbi Antiproteinuric effect of chemokine C-C motif ligand 2 inhibition in subjects with acute proliferative lupus nephritis
    Alessandro Ble
    Angelini Research Center, Piazzale della Stazione, S Palomba, Pomezia, Italy
    Am J Nephrol 34:367-72. 2011
    ..To test the role of chemokine C-C motif ligand 2 (CCL2) in the pathogenesis of lupus nephritis (LN), we evaluated the effects of CCL2 inhibition by bindarit therapy in patients with systemic lupus and active renal disease...
  17. pmc c-Yes regulates cell adhesion at the blood-testis barrier and the apical ectoplasmic specialization in the seminiferous epithelium of rat testes
    Xiang Xiao
    Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY 10065, USA
    Int J Biochem Cell Biol 43:651-65. 2011
    ..In summary, c-Yes regulates BTB and apical ES integrity by maintaining proper distribution of integral membrane proteins and actin filament organization at these sites...
  18. pmc Par3/Par6 polarity complex coordinates apical ectoplasmic specialization and blood-testis barrier restructuring during spermatogenesis
    Elissa W P Wong
    Population Council, 1230 York Avenue, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 105:9657-62. 2008
    ....
  19. ncbi Isoform-specific phosphoinositide 3-kinase inhibitors exert distinct effects in solid tumors
    Kyle A Edgar
    Cancer Signaling and Translational Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    Cancer Res 70:1164-72. 2010
    ..Our results imply that patients with PTEN-negative tumors may preferentially benefit from treatment with a class I PI3K inhibitor that is capable of inhibiting the p110beta isoform...
  20. ncbi Inhibitory effect of YC-1 on the hypoxic induction of erythropoietin and vascular endothelial growth factor in Hep3B cells
    Y S Chun
    Department of Pharmacology and Heart Research Institute, BK21 Human Life Sciences, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, 110-799, Seoul, South Korea
    Biochem Pharmacol 61:947-54. 2001
    ..This observation implies that the inhibitory effects of YC-1 on hypoxic responses can be developed to suppress EPO-overproduction by tumor cells and tumor angiogenesis...
  21. pmc ABT-869, a multitargeted receptor tyrosine kinase inhibitor: inhibition of FLT3 phosphorylation and signaling in acute myeloid leukemia
    Deepa B Shankar
    Division of Hematology Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
    Blood 109:3400-8. 2007
    ..In tumors, ABT-869 inhibited FLT3 phosphorylation, induced apoptosis (transferase-mediated dUTP nick-end labeling [TUNEL]) and decreased proliferation (Ki67). ABT-869 is under clinical development for AML...
  22. ncbi Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study
    Jean Philippe Spano
    Hopital de la Pitie Salpetriere, Paris, France
    Lancet 371:2101-8. 2008
    ..The aim of this study was to assess the safety and efficacy of gemcitabine plus axitinib versus gemcitabine alone...
  23. ncbi The selective VEGFR1-3 inhibitor axitinib (AG-013736) shows antitumor activity in human neuroblastoma xenografts
    Jochen Rossler
    UPRES EA 3535, Pharmacology and New Anticancer Treatments, University Paris Sud, Institut Gustave Roussy, Villejuif, France
    Int J Cancer 128:2748-58. 2011
    ..Axitinib has potent antiangiogenic properties that may warrant further evaluation in neuroblastoma...
  24. ncbi Does axitinib (AG-01376) have a future role in metastatic renal cell carcinoma and other malignancies?
    Robert Goldstein
    Department of Oncology, St George s Hospital, London, SW17 0QT, UK
    Expert Rev Anticancer Ther 10:1545-57. 2010
    ..It is now being investigated in two Phase III trials in metastatic renal cell carcinoma and in Phase II trials in a range of tumor types. These trials will determine whether axitinib is an effective and safe antiangiogenic therapy...
  25. pmc Adjudin-mediated Sertoli-germ cell junction disassembly affects Sertoli cell barrier function in vitro and in vivo
    Linlin Su
    Population Council, Center for Biomedical Research, New York, NY 10065, USA
    Int J Biochem Cell Biol 42:1864-75. 2010
    ..These results illustrate that a unique mechanism exists to maintain blood-testis barrier integrity at all costs, irrespective of the presence of germ cells in the seminiferous epithelium of the testis...
  26. ncbi Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer
    Hope S Rugo
    University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Ave, Second Floor, Box 1710, San Francisco, CA 94115, USA
    J Clin Oncol 29:2459-65. 2011
    ..This multicenter, randomized, double-blind, phase II study assessed safety and efficacy of axitinib plus docetaxel in metastatic breast cancer (MBC)...
  27. ncbi Pleiotropic effects of YC-1 selectively inhibit pathological retinal neovascularization and promote physiological revascularization in a mouse model of oxygen-induced retinopathy
    M DeNiro
    Research Department, King Khaled Eye Specialist Hospital, Aruba Street, P O Box 7191, Riyadh 11462, Kingdom of Saudi Arabia
    Mol Pharmacol 77:348-67. 2010
    ..The pleiotropic effects of YC-1 allude to its possible use as a promising therapeutic iNOS inhibitor candidate for the treatment of retinal neovascularization...
  28. ncbi 7-Nitroindazole potentiates the anticonvulsant action of some second-generation antiepileptic drugs in the mouse maximal electroshock-induced seizure model
    J J Luszczki
    Department of Pathophysiology, Medical University of Lublin, Lublin, Poland
    J Neural Transm 113:1157-68. 2006
    ....
  29. ncbi Axitinib--a selective inhibitor of the vascular endothelial growth factor (VEGF) receptor
    Ronan J Kelly
    National Cancer Institute, Medical Oncology Branch, Center for Cancer Research, Bethesda, MD 20892, USA
    Target Oncol 4:297-305. 2009
    ..Ongoing Phase III studies in pancreatic and metastatic renal cell carcinoma should help to determine the optimum utilization of these agents at the appropriate stage of disease...
  30. pmc Therapeutic efficacy and safety of paclitaxel/lonidamine loaded EGFR-targeted nanoparticles for the treatment of multi-drug resistant cancer
    Lara Milane
    Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, United States of America
    PLoS ONE 6:e24075. 2011
    ....
  31. ncbi Axitinib modulates hypoxia-induced blood-retina barrier permeability and expression of growth factors
    Marcus Kernt
    Department of Ophthalmology, Ludwig Maximilians University, Munich, Germany
    Growth Factors 30:49-61. 2012
    ..Axitinib significantly reduced hypoxia-induced effects on HUVEC and RPE cells. Our in vitro results suggest that axitinib may have promising properties as a potential treatment for diabetic macular edema...
  32. pmc Inhibition of reactive gliosis prevents neovascular growth in the mouse model of oxygen-induced retinopathy
    Michael Deniro
    Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
    PLoS ONE 6:e22244. 2011
    ..In addition, the study reveals that YC-1 may exert promising therapeutic effects in the treatment of retinal and neuronal pathologies...
  33. ncbi Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study
    Olivier Rixe
    Pitie Salpetriere Hospital, University of Paris, Paris, France
    Lancet Oncol 8:975-84. 2007
    ..We aimed to assess the activity and safety of axitinib in patients with metastatic renal-cell cancer who had failed on previous cytokine-based treatment...
  34. ncbi Inhibition of hypoxia inducible factor 1α expression suppresses the progression of esophageal squamous cell carcinoma
    Hong Zhu
    Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
    Cancer Biol Ther 11:981-7. 2011
    ..In conclusion, our results provide new insight into the potential role of HIF-1α in esophageal squamous cell carcinoma and open up the possibility of inhibiting HIF-1α for targeted therapy of esophageal squamous cell carcinoma...
  35. ncbi YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1
    Eun Jin Yeo
    Department of Pharmacology, BK21 Human Life Sciences, Seoul National University College of Medicine, Seoul, Korea
    J Natl Cancer Inst 95:516-25. 2003
    ..We tested whether YC-1 inhibits HIF-1 and tumor growth in vivo...
  36. ncbi Effects of YC-1 on hypoxia-inducible factor 1 alpha in hypoxic human bladder transitional carcinoma cell line T24 cells
    Yangle Li
    Department of Urology, Second Xiangya Hospital, Central South University, Changsha, China
    Urol Int 88:95-101. 2012
    ....
  37. ncbi Modulation of the tumor microvasculature by phosphoinositide-3 kinase inhibition increases doxorubicin delivery in vivo
    Naseer Qayum
    Gray Institute for Radiation Oncology and Biology, Oxford University, Oxford, United Kingdom
    Clin Cancer Res 18:161-9. 2012
    ..On the basis of that result, we asked whether inhibition of PI3K would improve chemotherapy delivery...
  38. ncbi Intrinsic and acquired forms of resistance against the anticancer ruthenium compound KP1019 [indazolium trans-[tetrachlorobis(1H-indazole)ruthenate (III)] (FFC14A)
    P Heffeter
    Institute of Cancer Research, Borschkegasse 8a, 1090 Vienna, Austria
    J Pharmacol Exp Ther 312:281-9. 2005
    ..In summary, the likeliness of acquiring insensitivity to KP1019 during therapy is expected to be low, and resistance should not be based on overexpression of drug efflux transporters...
  39. ncbi The anti-angiogenesis agent, AG-013736, has minimal activity in elderly patients with poor prognosis acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
    Francis J Giles
    Department of Leukemia, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, TX 77030, USA
    Leuk Res 30:801-11. 2006
    ..AG-01736 had minimal biologic or clinical activity in this elderly patient population...
  40. ncbi Inhibition of in-stent stenosis by oral administration of bindarit in porcine coronary arteries
    Armando Ialenti
    Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy
    Arterioscler Thromb Vasc Biol 31:2448-54. 2011
    ..The aim of the current study was to evaluate the efficacy of bindarit on in-stent stenosis in the preclinical porcine coronary stent model...
  41. ncbi YC-1-induced cyclooxygenase-2 expression is mediated by cGMP-dependent activations of Ras, phosphoinositide-3-OH-kinase, Akt, and nuclear factor-kappaB in human pulmonary epithelial cells
    Ming Shyan Chang
    Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu Hsing Street, Taipei 110, Taiwan
    Mol Pharmacol 66:561-71. 2004
    ....
  42. ncbi CZE-ICP-MS as a tool for studying the hydrolysis of ruthenium anticancer drug candidates and their reactivity towards the DNA model compound dGMP
    Michael Groessl
    Institute of Inorganic Chemistry, University of Vienna, Waehringer Street 42, A 1090 Vienna, Austria
    J Inorg Biochem 102:1060-5. 2008
    ..RAPTA-C was found to hydrolyze fastest and showed the highest reactivity toward the DNA model compound, whereas KP418 was the most stable compound in both these respects...
  43. pmc YC-1 inhibited human platelet aggregation through NO-independent activation of soluble guanylate cyclase
    C C Wu
    Pharmacological Institute, College of Medicine, National Taiwan University, Taipei
    Br J Pharmacol 116:1973-8. 1995
    ..7. These results would suggest that YC-1 activates sGC of human platelets by a NO-dependent mechanism, and exerts its antiplatelet effects through the sGC/cyclic GMP pathway...
  44. ncbi Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor
    Daniel H Albert
    Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, R47J, Building AP9 2, 100 Abbott Park Road, Abbott Park, IL 60064 3500, USA
    Mol Cancer Ther 5:995-1006. 2006
    ..08 microg/mL, >or=7 hours) than with plasma area under the curve or Cmax. These results support clinical assessment of ABT-869 as a therapeutic agent for cancer...
  45. ncbi Preconditioning protects against oxidative injury involving hypoxia-inducible factor-1 and vascular endothelial growth factor in cultured astrocytes
    Percy W Y Chu
    Molecular Neuropharmacology, Florey Neuroscience Institutes, University of Melbourne, VIC 3010, Australia
    Eur J Pharmacol 633:24-32. 2010
    ....
  46. ncbi Amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with bindarit, an inhibitor of monocyte chemotactic proteins
    Nestor E Rulli
    Faculty of Applied Science, University of Canberra, Canberra, ACT, Australia
    Arthritis Rheum 60:2513-23. 2009
    ..The aim of the present investigations was to determine whether bindarit, an inhibitor of monocyte chemotactic protein (MCP) synthesis, could ameliorate alphavirus-induced rheumatic disease in mice...
  47. ncbi Enhanced activation of STAT pathways and overexpression of survivin confer resistance to FLT3 inhibitors and could be therapeutic targets in AML
    Jianbiao Zhou
    Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
    Blood 113:4052-62. 2009
    ....
  48. ncbi Modulating the hypoxia-inducible factor signaling pathway as a therapeutic modality to regulate retinal angiogenesis
    M DeNiro
    Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
    Exp Eye Res 89:700-17. 2009
    ....
  49. pmc Epidermal growth factor receptor pathway substrate 8 (Eps8) is a novel regulator of cell adhesion and the blood-testis barrier integrity in the seminiferous epithelium
    Pearl P Y Lie
    Center for Biomedical Research, Population Council, 1230 York Ave, New York, NY 10065, USA
    FASEB J 23:2555-67. 2009
    ....
  50. ncbi A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1{alpha}
    Shan Hua Li
    Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea
    Mol Cancer Ther 7:3729-38. 2008
    ..Given these results, we suggest that the functional inactivation of HIF-alpha contributes to the YC-1-induced deregulation of hypoxia-induced genes...
  51. ncbi Suppression of HER2/HER3-mediated growth of breast cancer cells with combinations of GDC-0941 PI3K inhibitor, trastuzumab, and pertuzumab
    Evelyn Yao
    Department of Cancer Signaling, Genentech, Inc, South San Francisco, California, USA
    Clin Cancer Res 15:4147-56. 2009
    ..We therefore investigated the combinatorial activity of GDC-0941, a novel class I PI3K inhibitor, with standard-of-care therapies for HER2-amplified breast cancer...
  52. ncbi From bench to bedside--preclinical and early clinical development of the anticancer agent indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019 or FFC14A)
    Christian G Hartinger
    Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, A 1090 Vienna, Austria
    J Inorg Biochem 100:891-904. 2006
    ..In this review, the preclinical and early clinical development of KP1019 - from bench to bedside - is recapitulated...
  53. ncbi Increased apoptotic efficacy of lonidamine plus arsenic trioxide combination in human leukemia cells. Reactive oxygen species generation and defensive protein kinase (MEK/ERK, Akt/mTOR) modulation
    Eva Calviño
    Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Cientificas, Madrid, Spain
    Biochem Pharmacol 82:1619-29. 2011
    ..And (iii) conversely, the pro-oxidant action of lonidamine potentiates the apoptotic efficacy of ATO as an anti-leukemic agent...
  54. ncbi Multicenter, phase II study of axitinib, a selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, in patients with metastatic melanoma
    John Fruehauf
    University of California, Irvine, Orange, 92868, USA
    Clin Cancer Res 17:7462-9. 2011
    ....
  55. ncbi Effects of YC-1 on hypoxia-inducible factor 1-driven transcription activity, cell proliferative vitality, and apoptosis in hypoxic human pancreatic cancer cells
    Qiu Zhao
    Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
    Pancreas 34:242-7. 2007
    ..To investigate the effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) on HIF-1-driven transcription activity, cell proliferative vitality, and apoptosis in hypoxic human pancreatic cancer cells...
  56. ncbi Effects of YC-1 targeting hypoxia-inducible factor 1 alpha in oesophageal squamous carcinoma cell line Eca109 cells
    Yadong Feng
    Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People s Republic of China
    Cell Biol Int 35:491-7. 2011
    ..YC-1 arrested cell growth and inhibited cell migration activities in Eca109 cells. These results suggest that YC-1 may be a chemotherapy candidate against oesophageal squamous cancers...
  57. ncbi Inhibitory mechanisms of YC-1 and PMC in the induction of iNOS expression by lipoteichoic acid in RAW 264.7 macrophages
    George Hsiao
    Graduate Institute of Pharmacology, Taipei Medical University, 250 Wu Shing Street, Taipei 110, Taiwan, ROC
    Biochem Pharmacol 67:1411-9. 2004
    ..YC-1 may be mediated by increasing cyclic GMP, followed by, at least partly, inhibition of JNK/SAPK and NF-kappaB activations, thereby leading to inhibition of iNOS expression...
  58. ncbi Enhancement of learning behaviour by a potent nitric oxide-guanylate cyclase activator YC-1
    Wei Lin Chien
    Pharmacological Institute, College of Medicine, National Taiwan University, No 1, Sec 1, Jen Ai Road, Taipei, Taiwan
    Eur J Neurosci 21:1679-88. 2005
    ..YC-1 is thus a good drug candidate for the improvement of learning and memory...
  59. ncbi Phase I and biomarker study of ABT-869, a multiple receptor tyrosine kinase inhibitor, in patients with refractory solid malignancies
    Chiung Ing Wong
    Department of Hematology Oncology, National University Hospital, National University of Singapore, Singapore 119074
    J Clin Oncol 27:4718-26. 2009
    ..To determine the safety and tolerability of ABT-869 at escalating doses and its effects on biomarkers relevant for antiangiogenic activity in patients with solid malignancies...
  60. pmc The anti-inflammatory agent bindarit inhibits neointima formation in both rats and hyperlipidaemic mice
    Gianluca Grassia
    Department of Experimental Pharmacology, University of Naples Federico II, Via Domenico Montesano, 49, 80131 Naples, Italy
    Cardiovasc Res 84:485-93. 2009
    ....
  61. pmc Bindarit: an anti-inflammatory small molecule that modulates the NFκB pathway
    Eugenio Mora
    Center for Epigenetics and Metabolism, School of Medicine, University of California at Irvine, Irvine, CA, USA
    Cell Cycle 11:159-69. 2012
    ..These findings pave the way for future applications of bindarit as modulator of the inflammatory response...
  62. ncbi Pharmacokinetic-pharmacodynamic modeling of tumor growth inhibition and biomarker modulation by the novel phosphatidylinositol 3-kinase inhibitor GDC-0941
    Laurent Salphati
    Departments of Drug Metabolism and Pharmacokinetics, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA
    Drug Metab Dispos 38:1436-42. 2010
    ..1 xenograft...
  63. ncbi NO-independent stimulators of soluble guanylate cyclase
    A Straub
    Institute of Medicinal Chemistry, Pharma Research Centre, Bayer AG, Wuppertal, FRG
    Bioorg Med Chem Lett 11:781-4. 2001
    ..Several pyrazolopyridinylpyrimidines are shown to relax aortic rings and revealed a long-lasting blood pressure lowering effect in rats after oral application...
  64. ncbi [Os(IV)Cl(5)(Hazole)](-) complexes: synthesis, structure, spectroscopic properties, and antiproliferative activity
    Gabriel E Büchel
    University of Vienna, Institute of Inorganic Chemistry, Austria
    Inorg Chem 48:10737-47. 2009
    ..Replacement of azolium cations by sodium had significant effects; cytotoxicity increased in the case of the pyrazole system from 3 (A549) to the 5.5-fold (CH1)...
  65. ncbi AG-013736, a novel inhibitor of VEGF receptor tyrosine kinases, inhibits breast cancer growth and decreases vascular permeability as detected by dynamic contrast-enhanced magnetic resonance imaging
    Lisa J Wilmes
    Department of Radiology, University of California San Francisco, San Francisco, CA 94143 1290, USA
    Magn Reson Imaging 25:319-27. 2007
    ..Furthermore, the correlative relationship between microvasculature changes and tumor growth inhibition supports DCE-MRI methods as a biomarker of VEGF receptor target inhibition with potential clinical utility...
  66. ncbi Phase II study of lonidamine and diazepam in the treatment of recurrent glioblastoma multiforme
    Stephane Oudard
    Department of Oncology, Hopital Europeen Georges Pompidou, Paris, France
    J Neurooncol 63:81-6. 2003
    ..LND plus diazepam may be interesting in the adjuvant setting or associated to chemotherapy to act on different targets and increase the therapeutic index...
  67. ncbi Synergistic antileukemic effects between ABT-869 and chemotherapy involve downregulation of cell cycle-regulated genes and c-Mos-mediated MAPK pathway
    J Zhou
    Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
    Leukemia 22:138-46. 2008
    ..Thus, a clinical trial using sequence-dependent combination therapy with ABT-869 in AML is warranted...
  68. ncbi Serum-protein interactions with anticancer Ru(III) complexes KP1019 and KP418 characterized by EPR
    Naniye Cetinbas
    Department of Chemistry, Simon Fraser University, Burnaby, BC, Canada
    J Biol Inorg Chem 15:131-45. 2010
    ..In the presence of apo-hsTf, KP418 interacts directly with the protein through exchange of ligands, as observed with KP1019...
  69. ncbi Meta-analysis of contribution of genetic polymorphisms in drug-metabolizing enzymes or transporters to axitinib pharmacokinetics
    Meghan Brennan
    Pfizer Research Center of Emphasis for DNA and Biofluids Biobank, Groton, CT, USA
    Eur J Clin Pharmacol 68:645-55. 2012
    ..The potential contribution of polymorphisms in genes encoding these enzymes and transporters to axitinib pharmacokinetic variability was assessed...
  70. ncbi 5-(pyridinon-1-yl)indazoles and 5-(furopyridinon-5-yl)indazoles as MCH-1 antagonists
    Matthew D Surman
    AMRI, 26 Corporate Circle, Albany, NY 12212 5098, USA
    Bioorg Med Chem Lett 20:7015-9. 2010
    A new series of 5-(pyridinon-1-yl)indazoles with MCH-1 antagonist activity were synthesized...
  71. ncbi YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole] inhibits endothelial cell functions induced by angiogenic factors in vitro and angiogenesis in vivo models
    Shiow Lin Pan
    Pharmacological Institute, College of Medicine, National Taiwan University, 1 Jen Ai Road, Section 1, Taipei, Taiwan
    J Pharmacol Exp Ther 314:35-42. 2005
    ..YC-1 may be useful for treating angiogenesis-dependent human diseases such as cancer...
  72. ncbi ABT-869, a multitargeted receptor tyrosine kinase inhibitor, reduces tumor microvascularity and improves vascular wall integrity in preclinical tumor models
    Fang Jiang
    Abbott Laboratories, Abbott Park, Illinois 60064 3537, USA
    J Pharmacol Exp Ther 338:134-42. 2011
    ..Taken together, decreases in vascular permeability and changes in vascular integrity observed in these studies define the mode of action of ABT-869 and may aid in optimizing the timing of therapeutic window for combination therapies...
  73. ncbi YC-1 induces heat shock protein 70 expression and prevents oxidized LDL-mediated apoptosis in vascular smooth muscle cells
    Yi Nan Liu
    Phamacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
    Shock 30:274-9. 2008
    ..According to our observations, YC-1 would be an effectively pharmacological hsp70 inducer that can be used as a cytoprotective agent in vascular diseases...
  74. ncbi Consecutive condensation, C-N and N-N bond formations: a copper- catalyzed one-pot three-component synthesis of 2H-indazole
    Manian Rajesh Kumar
    Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju, 500 757, Republic of Korea
    Org Lett 13:3542-5. 2011
    2H-Indazoles are synthesized using copper-catalyzed, one-pot, three-component reactions of 2-bromobenzaldehydes, primary amines, and sodium azide. A copper catalyst plays the key role in the formation of C-N and N-N bonds...
  75. ncbi Benzotriazoles and indazoles are scaffolds with biological activity against Entamoeba histolytica
    Fabian López-Vallejo
    Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St Lucie, FL 34987, USA
    J Biomol Screen 16:862-8. 2011
    ..The novel compounds have similar properties to approved drugs. Compounds with novel scaffolds represent promising starting points of an optimization program against E. histolytica...
  76. ncbi Amorphous solid dispersion enhances permeation of poorly soluble ABT-102: true supersaturation vs. apparent solubility enhancement
    Kerstin J Frank
    Institute of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK 5230 Odense M, Denmark
    Int J Pharm 437:288-93. 2012
    ..Overall, a good correlation between permeation rate and molecular solubility but not apparent solubility was seen...
  77. ncbi YC-1 attenuates hypoxia-induced pulmonary arterial hypertension in mice
    Jin Won Huh
    Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
    Pulm Pharmacol Ther 24:638-46. 2011
    ..Recently, direct activators of soluble guanylyl cyclase (sGC) have been tested as a novel therapeutic modality in experimental models of pulmonary arterial hypertension (PAH)...
  78. pmc Monitoring tumor response to linifanib therapy with SPECT/CT using the integrin αvβ3-targeted radiotracer 99mTc-3P-RGD2
    Shundong Ji
    School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA
    J Pharmacol Exp Ther 346:251-8. 2013
    ..Longitudinal imaging using (99m)Tc-3P-RGD2 SPECT/CT may be a useful tool for monitoring the downstream biologic effects of linifanib therapy. ..
  79. pmc En route to osmium analogues of KP1019: synthesis, structure, spectroscopic properties and antiproliferative activity of trans-[Os(IV)Cl4(Hazole)2]
    Gabriel E Büchel
    University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A 1090 Vienna, Austria
    Inorg Chem 50:7690-7. 2011
    ..Their antiproliferative acitivity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (nonsmall cell lung carcinoma), and SW480 (colon carcinoma) is reported...
  80. ncbi Salutary properties of YC-1 in the cardiovascular and hematological systems
    David Anthony Tulis
    Cardiovascular Disease Research Program, J L Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, 700 George Street, Durham, North Carolina 27707, USA
    Curr Med Chem Cardiovasc Hematol Agents 2:343-59. 2004
    ....
  81. pmc Characterization of the novel nitric oxide synthase inhibitor 7-nitro indazole and related indazoles: antinociceptive and cardiovascular effects
    P K Moore
    Biomedical Sciences Division, King s College, University of London
    Br J Pharmacol 110:219-24. 1993
    ..Accordingly, 7-NI (or a derivative thereof) may provide an alternative approach to the development of novel antinociceptive drugs...
  82. pmc Inhibition of rat cerebellar nitric oxide synthase by 7-nitro indazole and related substituted indazoles
    R C Babbedge
    Biomedical Sciences Division, King s College, University of London
    Br J Pharmacol 110:225-8. 1993
    ..Indazole-based inhibitors of NOS may prove useful tools with which to evaluate the biological roles of nitric oxide in the central nervous system...
  83. ncbi A new alkaloid and its artificial derivative with an indazole ring from Nigella glandulifera
    Yu Ming Liu
    Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haidian District, PR China
    Chem Pharm Bull (Tokyo) 52:454-5. 2004
    ..Their structures were established by spectral analysis, including two-dimensional (2D)-NMR spectroscopy. Nigeglanine (1) is the third natural product determined to contain an indazole nucleus...
  84. ncbi Aminopiperidine indazoles as orally efficacious melanin concentrating hormone receptor-1 antagonists
    Anil Vasudevan
    Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA
    Bioorg Med Chem Lett 15:5293-7. 2005
    ..Compounds 19 and 28, two of the more potent compounds identified in this study, were characterized by high exposure in the brain and demonstrated robust efficacy when dosed in diet-induced obese mice...
  85. pmc Axitinib for the management of metastatic renal cell carcinoma
    Bernard Escudier
    Institut Gustave Roussy, Villejuif, France
    Drugs R D 11:113-26. 2011
    ..These results will help to determine the place of axitinib in the mRCC treatment algorithm...
  86. ncbi YC-1 [3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl Indazole] exhibits a novel antiproliferative effect and arrests the cell cycle in G0-G1 in human hepatocellular carcinoma cells
    Shih Wei Wang
    Pharmacological Institutes, College of Medicine, National Taiwan University, 1 Jen Ai Road, sect 1, Taipei, Taiwan
    J Pharmacol Exp Ther 312:917-25. 2005
    ..Because of this, YC-1 is a potential antitumor agent worthy of further investigation...
  87. ncbi Synthesis of indazoles by the [3+2] cycloaddition of diazo compounds with arynes and subsequent acyl migration
    Zhijian Liu
    Department of Chemistry, Iowa State University, Ames, Iowa 50011, USA
    J Org Chem 73:219-26. 2008
    ..efficient approach to a wide range of potentially biologically and pharmaceutically interesting substituted indazoles in good to excellent yields under mild reaction conditions...
  88. ncbi YC-1 inhibits proliferation of human vascular endothelial cells through a cyclic GMP-independent pathway
    Hun Kung Hsu
    Graduate Institute of Medical Sciences, Taipei Medical University, 250 Wu Hsing Street, Taipei 110, Taiwan, ROC
    Biochem Pharmacol 66:263-71. 2003
    ..This YC-1-induced antiproliferation effect in HUVEC is via a cyclic GMP-independent pathway...
  89. ncbi Chromophore-modified bis-benzo[g]indole carboxamides: synthesis and antiproliferative activity of bis-benzo[g]indazole-3-carboxamides and related dimers
    Gerard A Pinna
    Dipartimento Farmaco Chimico Tossicologico, Universita di Sassari, via F Muroni 23 A, 07100 Sassari, Italy
    Farmaco 58:749-63. 2003
    ..Finally, viscosity measurement of 2f with poly(dA-dT)(2), confirmed that these promising compounds behaved as typical DNA-intercalating agents...
  90. ncbi Synthesis and antiproliferative activity of triazenoindazoles and triazenopyrazoles: a comparative study
    Giuseppe Daidone
    Dipartimento di Chimica e Tecnologie Farmaceutiche, Universita degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy
    Eur J Med Chem 39:219-24. 2004
    ..The (1)H-NMR spectra showed that the rotational barrier around the N(2)-N(3) bond in the triazene group can be influenced both by the position of this group in the indazole nucleus and by the substitution pattern in the benzene moiety...
  91. ncbi New anticancer strategies targeting HIF-1
    Eun Jin Yeo
    Department of Pharmacology, College of Medicine, Seoul National University, 28 Yongon Dong, Chongno Gu, 110 799, Republic of Korea
    Biochem Pharmacol 68:1061-9. 2004
    ..Moreover, it halted tumor growth in immunodeficient mice without serious toxicity during the treatment period. Thus, we propose that YC-1 is a good lead compound for the development of new anti-HIF-1, anticancer agents...
  92. ncbi Synthesis of furopyrazole analogs of 1-benzyl-3-(5-hydroxymethyl-2-furyl)indazole (YC-1) as novel anti-leukemia agents
    Li Chen Chou
    Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan
    Bioorg Med Chem 15:1732-40. 2007
    ..Therefore, compound 1 is identified here as a new lead compound of cell differentiating agent and apoptosis inducer for further development of new anti-leukemia agents...
  93. pmc Zinc transporter 8 (ZnT8) expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy
    Michael Deniro
    Research Department, King Khaled Eye Specialist Hospital Affiliate of the Wilmer Eye Institute of the Johns Hopkins Medicine, Riyadh, Saudi Arabia
    PLoS ONE 7:e50360. 2012
    ..Therefore, targeting ZnT8 provides a therapeutic strategy to combat neovascular eye diseases...
  94. ncbi Synthesis and biological evaluation of N-(7-indazolyl)benzenesulfonamide derivatives as potent cell cycle inhibitors
    L Bouissane
    Institut de Chimie Organique et Analytique, UMR CNRS 6005, Universite d Orleans, BP 6759, France
    Bioorg Med Chem 14:1078-88. 2006
    ..These compounds were evaluated for their antiproliferative activities toward L1210 murine leukemia cells. One of them, 4-methoxy-N-(3-chloro-7-indazolyl)benzenesulfonamide, was identified as the most potent with an IC(50) of 0.44 microM...
  95. ncbi YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF-kappaB signaling to HIF-1alpha accumulation during hypoxia
    H L Sun
    Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
    Oncogene 26:3941-51. 2007
    ..Overall, we identify a potential molecular mechanism whereby YC-1 serves to reduce HIF-1 expression...
  96. ncbi Mitochondrial targeting drug lonidamine triggered apoptosis in doxorubicin-resistant HepG2 cells
    Y C Li
    Department of Biochemistry, The Chinese University of Hong Kong, Shatin, People s Republic of China
    Life Sci 71:2729-40. 2002
    ..Taken together, our results suggest a potential use of LND as an anti-cancer drug to bypass drug resistance and to trigger tumour destruction through apoptosis in HepG2 and R-HepG2 cells...
  97. pmc Effect of rifampin on the pharmacokinetics of Axitinib (AG-013736) in Japanese and Caucasian healthy volunteers
    Y K Pithavala
    Pfizer Oncology, Pfizer Global Research and Development, La Jolla Laboratories, 101646 Science Center Drive, San Diego, CA 92121, USA
    Cancer Chemother Pharmacol 65:563-70. 2010
    ..Equal numbers of Japanese and Caucasian subjects were enrolled to assess the potential differences in axitinib pharmacokinetics between the two ethnicities...
  98. ncbi Protective effects of YC-1 against glutamate induced PC12 cell apoptosis
    Xiaofan Yang
    College of Medicine, Nankai University, Tianjin, China
    Cell Mol Neurobiol 31:303-11. 2011
    ..These results revealed that YC-1 might attenuate glutamate-induced PC12 cell apoptosis via a sGC-cGMP involved pathway...
  99. ncbi Human trabecular meshwork cell volume decrease by NO-independent soluble guanylate cyclase activators YC-1 and BAY-58-2667 involves the BKCa ion channel
    William M Dismuke
    Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, Florida 32610, USA
    Invest Ophthalmol Vis Sci 50:3353-9. 2009
    ..This study investigated the effects of the nitric oxide (NO)-independent activators of soluble guanylate cyclase (sGC), YC-1, and BAY-58-2667 on TM cell volume and the signal transduction pathways and ion channel involved...
  100. pmc Stable expression of HIF-1alpha in tubular epithelial cells promotes interstitial fibrosis
    Kuniko Kimura
    First Department of Internal Medicine, Nara Medical University, 840 Shijo, Kashihara, Nara 634 8522, Japan
    Am J Physiol Renal Physiol 295:F1023-9. 2008
    ..In conclusion, HIF-1alpha appears to be a critical contributor to the progression of renal fibrosis and could be a useful target for its treatment...
  101. ncbi A domain responsible for HIF-1alpha degradation by YC-1, a novel anticancer agent
    Hye Lim Kim
    Department of Pharmacology, Seoul National University College of Medicine, Chongno Gu, Seoul 110 799, Korea
    Int J Oncol 29:255-60. 2006
    ..However, their binding to HIF-1alpha was not affected by YC-1, suggesting that they are not involved in the YC-1 action. It is also suggested that YC-1 targets a novel pathway regulating HIF-1alpha stability...

Research Grants53

  1. Development of a Palladium-Catalyzed Direct N2-Arylation of Indazoles.
    Meredeth A McGowan; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Indazoles bearing aryl groups attached at the N2 position have become increasingly prevalent amongst novel drug candidates.1-4...
  2. 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]..
  3. NO-MEDIATED MODIFICATION OF NMDA RECEPTOR DURING HYPOXIA
    Om Mishra; Fiscal Year: 2008
    ..abstract_text> ..
  4. NO-MEDIATED MODIFICATION OF NMDA RECEPTOR DURING HYPOXIA
    Om Mishra; Fiscal Year: 2006
    ..abstract_text> ..
  5. Substituted Amphetamines: NO-Dependent Mechanisms
    Yossef Itzhak; Fiscal Year: 2005
    ....
  6. Reconsolidation and extinction processes in the treatment of drug addiction
    Yossef Itzhak; Fiscal Year: 2010
    ..abstract_text> ..
  7. Adolescent Exposure to Psychostimulants: Role of nNOS
    Yossef Itzhak; Fiscal Year: 2008
    ..Results of these studies would provide new information on mechanisms that underlie the development of hypersensitivity to these drugs from adolescence through adulthood. ..
  8. ITEM BANKING AND CAT FOR QUALITY OF LIFE OUTCOMES
    David Cella; Fiscal Year: 2008
    ..We will also monitor treatment/management changes, and evaluate acceptability of computer assessments and the perceived benefits of the recommendations. ..
  9. Cannabinoid Regulation of Basal Ganglia Glutamate and GABA
    SCOTT RAWLS; Fiscal Year: 2007
    ..Our outcomes will be a first step in determining whether blocking endocannabinoid inactivation offers any therapeutic advantage over direct activation of cannabinoid receptors with marijuana. [unreadable] [unreadable] [unreadable]..
  10. Can beta-lactam antibiotics decrease morphine physical dependence?
    SCOTT RAWLS; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  11. CO POISONING IN THE CONTEXT OF A REPERFUSION INJURY
    Stephen Thom; Fiscal Year: 2003
    ..The research plan is aimed to test the hypothesis that immune responses and the associated oxidative stress cause neurological injuries. ..
  12. TUMOR OXYGENATION, VASCULARIZATION, AND RADIORESPONSE
    Bruce Fenton; Fiscal Year: 2009
    ..These results with lead to the more rational and optimal design of effective combined therapies, thereby ultimately accelerating their implementation into clinical protocols. ..
  13. Development of cAMP Biosensor, High Content Imaging, and Functional GLP-1R aSSAYS
    Philip LoGrasso; Fiscal Year: 2010
    ....
  14. Mechanisms of Bax-mediated cell death in the MPTP model
    Serge Przedborski; Fiscal Year: 2007
    ..Collectively, the proposed studies should shed light on the molecular mechanisms of neurodegeneration in PD and help to identify new molecular targets for therapeutic intervention. ..
  15. Targeting AKT as a novel therapy in pancreatic cancer
    Richard Bold; Fiscal Year: 2007
    ..These results will provide mechanistic as well as pre-clinical data in support of our hypothesis and will allow for the development of novel therapy of human pancreatic cancer. [unreadable] [unreadable] [unreadable]..
  16. Estrogen and brain vascular inflammation in diabetics
    Dale Pelligrino; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  17. Behavioral Influences on Drug Tolerance
    James Smith; Fiscal Year: 2005
    ..Additionally, "multi-chamber" procedures will study generalization of those discriminative effects to performance of the same subjects in different circumstances. ..
  18. Molecular Basis Of Renal Cell Carcinoma Response to SU11428
    Robert J Motzer; Fiscal Year: 2011
    ..These tumor and cell line-based studies lay a foundation for further molecular studies aimed at understanding the sensitivity/resistance of RCC to SU11248. ..
  19. Junction Dynamics and Male Fertility Regulation
    C Yan Cheng; Fiscal Year: 2008
    ..In summary, these studies not only will define the regulation of AJ dynamics, they will identify new leads and innovative approaches for male contraceptive development. [unreadable] [unreadable]..
  20. Labeled Thymidine -- Development as A PET Imaging Agent
    Anthony Shields; Fiscal Year: 2008
    ..Our ultimate goal is to demonstrate that this approach is useful in evaluating both experimental and routine clinical treatment. ..
  21. Nephrology Training Grant
    Scott Thomson; Fiscal Year: 2008
    ..An interactive research environment and shared seminar programs between UCSD, Salk Institute, and numerous other research institutes in La Jolla further enhances the training program. ..
  22. An in vivo model to study blood-testis barrier dynamics
    C Yan Cheng; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  23. COX-2 Inhibitors, APC and Colon Cancer Prevention
    Kotha Subbaramaiah; Fiscal Year: 2009
    ..These studies will enhance our understanding of the mechanistic link between COX-2 and colorectal cancer and potentially assist us in optimizing the use of selective COX-2 inhibitors as therapy. ..
  24. AMYGDALOID FUNCTION IN FEAR CONDITIONING
    Stephen Maren; Fiscal Year: 2009
    ..The outcome of these experiments will have an important impact on current conceptions of both amygdaloid function and on clinical disorders of fear that depend on emotional learning and memory. ..
  25. Renin regulation by nitric oxide
    WILLIAM BEIERWALTES; Fiscal Year: 2007
    ..These studies should reveal the dual pathways by which NO can either inhibit or stimulate renin secretion. ..
  26. Angiotensin II Mediates Early Changes in Diabetic Kidney
    Helmy Siragy; Fiscal Year: 2007
    ..The proposed studies will help understand the mechanisms that are involved in diabetic the development of new therapeutic modalities to prevent or slowdown the development ..
  27. THALAMOSTRIATAL MECHANISMS OF MORPHINE ACTION
    Richard Harlan; Fiscal Year: 2003
    ..These studies should greatly extend our understanding of the role of thalamo-striatal circuits in the actions of morphine on the brain. ..
  28. SYNUCLEIN AND NIGRAL DOPAMINERGIC NEURON DEGENERATION
    Serge Przedborski; Fiscal Year: 2003
    ....
  29. NEUROTROPHINS AND AN ANIMAL MODEL OF FIBROMYALGIA
    ALICE LARSON; Fiscal Year: 2003
    ..If kainic acid activity proves to be a useful model of FMS, therapeutic options may be more readily developed for this disease. ..
  30. NITRIC OXIDE AND PROTEIN NITROTYROSINE IN THE MPTP MODEL
    Serge Przedborski; Fiscal Year: 2002
    ..This proposal contains a comprehensive set of experiments, which should provide important insights into the role of NO in MPTP toxicity. It should also shed light on the mechanism(s) of neurodegeneration in PD. ..
  31. AMYGDALOID FUNCTION IN FEAR CONDITIONING
    Stephen Maren; Fiscal Year: 2002
    ..The outcome of these experiments will have an important impact on current conceptions of both amygdaloid function and emotional learning and memory. ..
  32. G PROTEINS AND PAROTID SECRETORY GRANULE
    EILEEN WATSON; Fiscal Year: 2002
    ..These studies will also provide a framework for examining cellular biochemical defects in diseases relating to salivary dysfunction. ..
  33. Gene expression associated with the CNS reinforcing act*
    ZACHARY RODD HENRICKS; Fiscal Year: 2003
    ..The results of the proposed project will provide valuable information on neuronal systems and receptors within the extended amygdala involved in mediating the rewarding properties of alcohol. ..
  34. MOLECULAR MECHANISMS FOR POST-SYNAPTIC DEVELOPMENT
    David Bredt; Fiscal Year: 2004
    ..Also, because PSD-95 organizes signal transduction cascades downstream of the N-methyl-D-aspartate (NMDA) type glutamate receptor, this proposal has relevance for synaptic plasticity and neurodegeneration mediated by the NMDA receptor. ..
  35. NITRIC OXIDE AND IN VIVO BRAIN ARTERIOLAR RELAXATION
    Dale Pelligrino; Fiscal Year: 2004
    ..These studies will provide important new information regarding the mechanisms controlling a physiologic process vital to normal brain function and survival-cerebral arteriolar dilation. ..
  36. PET IMAGING OF DRUG KINETICS AND PATHWAYS
    Anthony Shields; Fiscal Year: 2002
    ..Our proposed study of [F-18]FAU with PET will provide information on the biodistribution of this new therapeutic agent and may provide a way to image tumor TS activity and proliferation. ..
  37. SYNAPTIC REGULATION OF NITRIC OXIDE
    David Bredt; Fiscal Year: 2005
    ..On the other hand, an extended "P-finger" of the NNOS PDZ domain binds to PSD-95 and PSD-93, postsynaptic density proteins that mediate synaptic clustering of NMDA receptors. ..
  38. ACTININ ASSOCIATED LIM PROTEIN & FSH MUSCULAR DYSTROPHY
    David Bredt; Fiscal Year: 2002
    ..The proposed studies will lead to a better understanding of formation and function of the myofiber cytoskeleton and may provide insight in the pathogenesis and treatment of FSHD. ..
  39. Workshop on Steroid Hormones and Brain Function
    Richard Harlan; Fiscal Year: 2002
    ..Thus, this meeting provides a unique opportunity for young investigators to gain insight into a rapidly evolving and important field of research. ..
  40. SALIVARY SECRETION-ROLE OF CALCIUM
    EILEEN WATSON; Fiscal Year: 2005
    ..Mechanisms/pathways involved in AA/metabolite-mediated cAMP signaling will be assessed by correlating MAPK activation with cAMP synthesis and degradation. ..
  41. AT2 Receptor Modulates Renal Angiotensin II Levels
    Helmy Siragy; Fiscal Year: 2005
    ..Data obtained from this proposal will lead to increased understanding of the pathophysiology of hypertension and development of novel therapies for its management. ..
  42. Effect of enriched environment on ALS neurodegeneration
    Serge Przedborski; Fiscal Year: 2005
    ..This development/exploratory project offers an high-risk/high-yield set of studies which may demonstrate, in an original way, how environment may impact on the occurrence and the progression of ALS. ..
  43. PARAMETERS AND MECHANISMS OF COCAINE TOLERANCE
    George King; Fiscal Year: 2001
    ....
  44. CLINICAL TRIALS AND MENTORING IN ONCOLOGY RESEARCH
    Robert Motzer; Fiscal Year: 2003
    ..One recently joined staff at MSKCC in the Genito-urinary Section. Mentoring of clinical trials is extended beyond fellowship to junior faculty members. ..
  45. Functional Infrared Imaging Predicts Radiation Mucositis
    Ezra Cohen; Fiscal Year: 2008
    ..Such a tool would have wide applicability in this patient population and would have tremendous impact on their treatment. [unreadable] [unreadable] [unreadable]..
  46. Rapamycin as an Antineoplastic Agent
    Ezra Cohen; Fiscal Year: 2006
    ..At the conclusion of the trial RAPA toxicity and effect on p-S6K will be defined over a range of doses as well as the MTD for use in future studies that will develop this agent. ..
  47. MID CAREER INVESTIGATOR AWARD
    Joan Schiller; Fiscal Year: 2004
    ....
  48. Nano-Structure Surfaces and Liquid Crystal Analysis
    Joan Schiller; Fiscal Year: 2005
    ..abstract_text> ..
  49. MECHANISMS OF CUTANEOUS ACTIVE VASODILATION
    Dean Kellogg; Fiscal Year: 2008
    ..In addition, intradermal microdialysis will be combined with measurements of bioavailable NO by NO-selective amperometric electrode to define further how the NO system functions in cutaneous active vasodilation. ..
  50. CCNU in NSCLC Patients with Methylation of the MGMT Gene
    Joan Schiller; Fiscal Year: 2003
    ..abstract_text> ..
  51. Phase I Clinical Trials of Anti-Cancer Agents
    Francis Giles; Fiscal Year: 2007
    ..abstract_text> ..