protein kinase inhibitors

Summary

Summary: Agents that inhibit PROTEIN KINASES.

Top Publications

  1. ncbi Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma
    Tony S Mok
    State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong
    N Engl J Med 361:947-57. 2009
  2. ncbi Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR
    Makoto Maemondo
    Miyagi Cancer Center, Miyagi, Japan
    N Engl J Med 362:2380-8. 2010
  3. ncbi Targeting PI3K signalling in cancer: opportunities, challenges and limitations
    Jeffrey A Engelman
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02129, USA
    Nat Rev Cancer 9:550-62. 2009
  4. ncbi Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study
    Caicun Zhou
    Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
    Lancet Oncol 12:735-42. 2011
  5. pmc Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
    Ramin Nazarian
    Division of Dermatology Department of Medicine, UCLA s Jonsson Comprehensive Cancer Center, 52 121 CHS, Los Angeles, California 90095 1750, USA
    Nature 468:973-7. 2010
  6. pmc The selectivity of protein kinase inhibitors: a further update
    Jenny Bain
    Division of Signal Transduction Therapy, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 408:297-315. 2007
  7. pmc mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt
    Kathryn E O'Reilly
    Program in Molecular Pharmacy and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Cancer Res 66:1500-8. 2006
  8. ncbi Erlotinib in previously treated non-small-cell lung cancer
    Frances A Shepherd
    Department of Medical Oncology, University Health Network, Princess Margaret Hospital Site, University of Toronto, Canada
    N Engl J Med 353:123-32. 2005
  9. ncbi Screening for epidermal growth factor receptor mutations in lung cancer
    Rafael Rosell
    Catalan Institute of Oncology and Autonomous University of Barcelona, Hospital Germans Trias i Pujol, Barcelona, Spain
    N Engl J Med 361:958-67. 2009
  10. pmc COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
    Cory M Johannessen
    Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 468:968-72. 2010

Detail Information

Publications339 found, 100 shown here

  1. ncbi Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma
    Tony S Mok
    State Key Laboratory in Oncology in South China, Sir YK Pao Centre for Cancer, Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong
    N Engl J Med 361:947-57. 2009
    ..Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer...
  2. ncbi Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR
    Makoto Maemondo
    Miyagi Cancer Center, Miyagi, Japan
    N Engl J Med 362:2380-8. 2010
    ....
  3. ncbi Targeting PI3K signalling in cancer: opportunities, challenges and limitations
    Jeffrey A Engelman
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02129, USA
    Nat Rev Cancer 9:550-62. 2009
    ..I focus on the advantages and drawbacks of different treatment strategies for targeting this pathway, the cancers that might respond best to these therapies and the challenges and limitations that confront their clinical development...
  4. ncbi Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study
    Caicun Zhou
    Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
    Lancet Oncol 12:735-42. 2011
    ..The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC...
  5. pmc Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
    Ramin Nazarian
    Division of Dermatology Department of Medicine, UCLA s Jonsson Comprehensive Cancer Center, 52 121 CHS, Los Angeles, California 90095 1750, USA
    Nature 468:973-7. 2010
    ....
  6. pmc The selectivity of protein kinase inhibitors: a further update
    Jenny Bain
    Division of Signal Transduction Therapy, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 408:297-315. 2007
    ..Despite being used widely, many of the compounds that we analysed were too non-specific for useful conclusions to be made, other than to exclude the involvement of particular protein kinases in cellular processes...
  7. pmc mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt
    Kathryn E O'Reilly
    Program in Molecular Pharmacy and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Cancer Res 66:1500-8. 2006
    ..Reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may have improved antitumor activity...
  8. ncbi Erlotinib in previously treated non-small-cell lung cancer
    Frances A Shepherd
    Department of Medical Oncology, University Health Network, Princess Margaret Hospital Site, University of Toronto, Canada
    N Engl J Med 353:123-32. 2005
    ....
  9. ncbi Screening for epidermal growth factor receptor mutations in lung cancer
    Rafael Rosell
    Catalan Institute of Oncology and Autonomous University of Barcelona, Hospital Germans Trias i Pujol, Barcelona, Spain
    N Engl J Med 361:958-67. 2009
    ..We evaluated the feasibility of large-scale screening for EGFR mutations in such patients and analyzed the association between the mutations and the outcome of erlotinib treatment...
  10. pmc COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
    Cory M Johannessen
    Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Nature 468:968-72. 2010
    ....
  11. ncbi Epidermal growth factor receptor mutations in lung cancer
    Sreenath V Sharma
    Massachusetts General Hospital Cancer Center and Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA
    Nat Rev Cancer 7:169-81. 2007
    ....
  12. ncbi Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS)
    Masahiro Fukuoka
    Kinki University School of Medicine, Osaka, Japan
    J Clin Oncol 29:2866-74. 2011
    ..This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status...
  13. pmc SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
    B L Bennett
    Signal Research Division, Celgene Corporation, 5555 Oberlin Drive, San Diego, CA 92121 USA
    Proc Natl Acad Sci U S A 98:13681-6. 2001
    ..Our study supports targeting JNK as an important strategy in inflammatory disease, apoptotic cell death, and cancer...
  14. ncbi A quantitative analysis of kinase inhibitor selectivity
    Mazen W Karaman
    Ambit Biosciences, 4215 Sorrento Valley Blvd, San Diego, California 92121, USA
    Nat Biotechnol 26:127-32. 2008
    ..We further investigate the impact of panel size and find that small assay panels do not provide a robust measure of selectivity...
  15. ncbi Comprehensive analysis of kinase inhibitor selectivity
    Mindy I Davis
    Ambit Biosciences, San Diego, California, USA
    Nat Biotechnol 29:1046-51. 2011
    ..Our findings will help to realize the direct enabling potential of genomics for drug development and basic research about cellular signaling...
  16. ncbi Lapatinib plus capecitabine for HER2-positive advanced breast cancer
    Charles E Geyer
    Allegheny Cancer Center, Allegheny General Hospital, Pittsburgh, PA 15212, USA
    N Engl J Med 355:2733-43. 2006
    ..In this trial, we compared lapatinib plus capecitabine with capecitabine alone in such patients...
  17. pmc RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF
    Poulikos I Poulikakos
    Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 464:427-30. 2010
    ..In agreement with this prediction, RAF inhibitors do not inhibit ERK signalling in cells that coexpress BRAF(V600E) and mutant RAS...
  18. pmc Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers
    Jeffrey A Engelman
    Nat Med 14:1351-6. 2008
    ..These in vivo studies suggest that inhibitors of the PI3K-mTOR pathway may be active in cancers with PIK3CA mutations and, when combined with MEK inhibitors, may effectively treat KRAS mutated lung cancers...
  19. pmc MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib
    James Bean
    Human Oncology and Pathogenesis Program, Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 104:20932-7. 2007
    ..Taken together, these data suggest that MET amplification occurs independently of EGFR(T790M) mutations and that MET may be a clinically relevant therapeutic target for some patients with acquired resistance to gefitinib or erlotinib...
  20. ncbi Targeting cancer with small molecule kinase inhibitors
    Jianming Zhang
    Dana Farber Cancer Institute, Department of Cancer Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Cancer 9:28-39. 2009
    ..This Review provides a broad overview of some of the approaches currently used to discover and characterize new kinase inhibitors...
  21. ncbi Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling
    Scott M Wilhelm
    Bayer HealthCare Pharmaceuticals, 340 Changebridge Road, P O Box 1000, Montville, NJ 07045 1000, USA
    Mol Cancer Ther 7:3129-40. 2008
    ..patients with advanced refractory solid tumors have poor prognosis, the clinical development of targeted protein kinase inhibitors offers hope for the future treatment of many cancers...
  22. pmc Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK
    Alice T Shaw
    Department of Pathology, Massachusetts General Hospital, Warren 501c, 55 Fruit St, Boston, MA 02114, USA
    J Clin Oncol 27:4247-53. 2009
    ..To aid in identification and treatment of these patients, we examined the clinical characteristics and treatment outcomes of patients who had NSCLC with and without EML4-ALK...
  23. pmc Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer
    William Pao
    Department of Medicine, Vanderbilt Ingram Cancer Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, Tennessee 37232 6307, USA
    Nat Rev Cancer 10:760-74. 2010
    ..This Review summarizes recent developments aimed at treating and ultimately curing the disease...
  24. pmc AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients
    Tracy T Batchelor
    Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Cancer Cell 11:83-95. 2007
    ..Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor...
  25. pmc Detection of mutations in EGFR in circulating lung-cancer cells
    Shyamala Maheswaran
    Massachusetts General Hospital Cancer Center, Boston 02129, USA
    N Engl J Med 359:366-77. 2008
    ..Molecular characterization of circulating tumor cells may provide a strategy for noninvasive serial monitoring of tumor genotypes during treatment...
  26. ncbi Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia
    Hagop Kantarjian
    Department of Leukemia, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    N Engl J Med 362:2260-70. 2010
    ..We assessed the efficacy and safety of dasatinib, as compared with imatinib, for the first-line treatment of chronic-phase CML...
  27. ncbi RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth
    Georgia Hatzivassiliou
    Genentech, South San Francisco, California 94080, USA
    Nature 464:431-5. 2010
    ..Furthermore, this work provides new insights into the therapeutic use of ATP-competitive RAF inhibitors...
  28. ncbi Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity
    Sauveur Michel Maira
    Oncology Disease Area, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH4002 Basel, Switzerland
    Mol Cancer Ther 7:1851-63. 2008
    ..Collectively, the preclinical data show that NVP-BEZ235 is a potent dual PI3K/mTOR modulator with favorable pharmaceutical properties. NVP-BEZ235 is currently in phase I clinical trials...
  29. ncbi Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study
    Federico Cappuzzo
    Department of Medical Oncology, Ospedale Civile di Livorno, Livorno, Italy
    Lancet Oncol 11:521-9. 2010
    ....
  30. ncbi mTOR and cancer: insights into a complex relationship
    David M Sabatini
    Whitehead Institute for Biomedical Research, MIT Department of Biology, 9 Cambridge Center, Cambridge, Massachusetts 02142 1479, USA
    Nat Rev Cancer 6:729-34. 2006
    ..The purpose is not to cover all aspects of mTOR history and signalling, but rather to foster discussion by presenting some occasionally provocative ideas...
  31. pmc Understanding resistance to EGFR inhibitors-impact on future treatment strategies
    Deric L Wheeler
    Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, WI 53705, USA
    Nat Rev Clin Oncol 7:493-507. 2010
    ..A greater understanding of the mechanisms that lead to EGFR resistance may provide valuable insights to help design new strategies that will enhance the impact of this promising class of inhibitors for the treatment of cancer...
  32. 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...
  33. ncbi Sorafenib in advanced clear-cell renal-cell carcinoma
    Bernard Escudier
    Department of Medicine, Institut Gustave Roussy, Villejuif, France
    N Engl J Med 356:125-34. 2007
    ..We conducted a phase 3, randomized, double-blind, placebo-controlled trial of sorafenib, a multikinase inhibitor of tumor-cell proliferation and angiogenesis, in patients with advanced clear-cell renal-cell carcinoma...
  34. pmc AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance
    Thomas O'Hare
    Division of Hematology and Medical Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR 97239, USA
    Cancer Cell 16:401-12. 2009
    ..Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML...
  35. pmc Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling
    Nikhil Wagle
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, D1542, Boston, MA, USA
    J Clin Oncol 29:3085-96. 2011
    ..These results provide an instructive framework for assessing mechanisms of acquired resistance to kinase inhibition and illustrate the use of emerging technologies in a manner that may accelerate personalized cancer medicine...
  36. 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...
  37. pmc Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2
    Morris E Feldman
    Howard Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, USA
    PLoS Biol 7:e38. 2009
    ..These potent new pharmacological agents complement rapamycin in the study of mTOR and its role in normal physiology and human disease...
  38. ncbi Phase I trial of the irreversible EGFR and HER2 kinase inhibitor BIBW 2992 in patients with advanced solid tumors
    Timothy A Yap
    Drug Development Unit, The Royal Marsden National Health Service Foundation Trust, and the Institute of Cancer Research, Sutton, Surrey, United Kingdom
    J Clin Oncol 28:3965-72. 2010
    ..A phase I study of continuous once-daily oral BIBW 2992 was conducted to determine safety, maximum-tolerated dose, pharmacokinetics (PK), food effect, and preliminary antitumor efficacy...
  39. ncbi Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia
    Giuseppe Saglio
    University of Turin, San Luigi Gonzaga Hospital, Orbassano, Turin, Italy
    N Engl J Med 362:2251-9. 2010
    ..We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase...
  40. pmc Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity
    Theonie Anastassiadis
    Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
    Nat Biotechnol 29:1039-45. 2011
    Small-molecule protein kinase inhibitors are widely used to elucidate cellular signaling pathways and are promising therapeutic agents...
  41. ncbi Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial
    Francois Xavier Mahon
    Laboratoire d Hématologie et Service des Maladies du Sang, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
    Lancet Oncol 11:1029-35. 2010
    ..We aimed to assess whether imatinib can be discontinued without occurrence of molecular relapse in patients in complete molecular remission (CMR) while on imatinib...
  42. ncbi Current development of mTOR inhibitors as anticancer agents
    Sandrine Faivre
    Service Inter Hospitalier de Cancrologie, Beaujon University Hospital, 100 Boulevard du General Leclerc, 92118 Clichy Cedex, France
    Nat Rev Drug Discov 5:671-88. 2006
    ..Here we review the clinical development of this drug class and look at future prospects for incorporating these agents into multitarget or multimodality strategies against cancer...
  43. pmc Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors
    A F Gazdar
    Hamon Center for Therapeutic Oncology Research and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Oncogene 28:S24-31. 2009
    ..Various second-generation EGFR TKIs are currently being evaluated and may have the potential to overcome T790M-mediated resistance by virtue of their irreversible inhibition of the receptor TK domain...
  44. pmc The specificities of protein kinase inhibitors: an update
    Jenny Bain
    Division of Signal Transduction Therapy, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 371:199-204. 2003
    ..33 microM) and p38-regulated/activated kinase (PRAK; IC(50)=1.0 microM)...
  45. ncbi Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma
    Gary Hudes
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    N Engl J Med 356:2271-81. 2007
    ..Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease...
  46. ncbi EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors
    Young Lim Choi
    Division of Functional Genomics, Jichi Medical University, Tochigi, Japan
    N Engl J Med 363:1734-9. 2010
    ..Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors. (Funded by the Ministry of Health, Labor, and Welfare of Japan, and others.)...
  47. ncbi Shared and separate functions of polo-like kinases and aurora kinases in cancer
    Susanne M A Lens
    Department of Medical Oncology and Cancer Genomics Centre, UMC Utrecht, Universiteitsweg 100, Stratenum 2 118, Utrecht 3584 CG, The Netherlands
    Nat Rev Cancer 10:825-41. 2010
    ..In this Review we discuss the implications of these novel insights on the clinical applicability of polo-like kinase and aurora kinase inhibitors...
  48. ncbi First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung
    Ji Youn Han
    National Cancer Center, Goyang, Republic of Korea
    J Clin Oncol 30:1122-8. 2012
    ..We compared efficacy of gefitinib with gemcitabine and cisplatin (GP) chemotherapy in this group of patients as first-line therapy...
  49. ncbi TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer
    Roy S Herbst
    University of Texas M D Anderson Cancer Center, Houston, USA
    J Clin Oncol 23:5892-9. 2005
    ..Erlotinib was combined with chemotherapy to determine if it could improve the outcome of patients with NSCLC...
  50. ncbi Protein kinases--the major drug targets of the twenty-first century?
    Philip Cohen
    Medical Research Council, Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Nat Rev Drug Discov 1:309-15. 2002
    ..Protein kinases have now become the second most important group of drug targets, after G-protein-coupled receptors. Here, I give a personal view of some of the most important advances that have shaped this field...
  51. ncbi The biology and clinical relevance of the PTEN tumor suppressor pathway
    Isabelle Sansal
    Department of Medical Oncology, Dana Farber Cancer Institute, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    J Clin Oncol 22:2954-63. 2004
    ..Akt kinase inhibitors are still in development; however, as a first test of this hypothesis, phase I and phase II trials of inhibitors of mTOR, namely, rapamycin and rapamycin analogs are underway...
  52. ncbi Sorafenib in advanced hepatocellular carcinoma
    Josep M Llovet
    Barcelona Clinic Liver Cancer Group, Institut d Investigacions Biomediques August Pi i Sunyer, Centro de Investigaciones en Red de Enfermedades Hepáticas y Digestivas Hospital Clínic Barcelona, Barcelona
    N Engl J Med 359:378-90. 2008
    ..A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma...
  53. ncbi The pharmacology of mTOR inhibition
    David A Guertin
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02141, USA
    Sci Signal 2:pe24. 2009
    ..Here, we summarize exciting findings regarding mTOR signaling and the outlook for mTOR inhibitors as tools to study the mTOR pathway and as drugs in the clinic...
  54. pmc Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity
    James Tsai
    Plexxikon, Inc, 91 Bolivar Drive, Berkeley, CA 94710, USA
    Proc Natl Acad Sci U S A 105:3041-6. 2008
    ....
  55. ncbi Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL
    Hagop Kantarjian
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77230 1402, USA
    N Engl J Med 354:2542-51. 2006
    ..Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50...
  56. pmc AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity
    Sarat Chandarlapaty
    Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cancer Cell 19:58-71. 2011
    ..Consistent with this model, we find that, in tumors in which AKT suppresses HER3 expression, combined inhibition of AKT and HER kinase activity is more effective than either alone...
  57. 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...
  58. ncbi AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity
    Christine M Chresta
    AstraZeneca, Cheshire, United Kingdom
    Cancer Res 70:288-98. 2010
    ..Notably, AZD8055 results in significant growth inhibition and/or regression in xenografts, representing a broad range of human tumor types. AZD8055 is currently in phase I clinical trials...
  59. ncbi EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study
    Robert Pirker
    Department of Medicine I, Medical University Vienna, Vienna, Austria
    Lancet Oncol 13:33-42. 2012
    ..To define patients benefiting most from cetuximab, we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients...
  60. pmc A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging
    Matilde Murga
    Genomic Instability Group, Spanish National Cancer Research Centre CNIO, Madrid, Spain
    Nat Genet 41:891-8. 2009
    ....
  61. ncbi Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5
    L Meijer
    CNRS, Station Biologique, Roscoff, France
    Eur J Biochem 243:527-36. 1997
    ..Through its unique selectivity for some cyclin-dependent kinases, roscovitine provides a useful antimitotic reagent for cell cycle studies and may prove interesting to control cells with deregulated cdc2, cdk2 or cdk5 kinase activities...
  62. pmc Safety and efficacy of everolimus, a mTOR inhibitor, as single agent in a phase 1/2 study in patients with myelofibrosis
    Paola Guglielmelli
    Department of Medical and Surgical Care, Section of Hematology, University of Florence, Florence, Italy
    Blood 118:2069-76. 2011
    ..These results provide proof-of-concept that targeting mTOR pathway in myelofibrosis may be clinically relevant...
  63. ncbi The CDK inhibitors in cancer research and therapy
    Jonas Cicenas
    Department of Medicine, Institute of Anatomy, University of Fribourg, Rte Albert Gockel 1, 1700, Fribourg, Switzerland
    J Cancer Res Clin Oncol 137:1409-18. 2011
    ..For this purpose, the targets, commercial availability and IC(50) values are provided for each inhibitor. The review will also provide an overview of the clinical studies performed with some of these inhibitors...
  64. ncbi Discovery and development of sorafenib: a multikinase inhibitor for treating cancer
    Scott Wilhelm
    Department of Cancer Research, Bayer Pharmaceuticals Corp, West Haven, Connecticut 06516, USA
    Nat Rev Drug Discov 5:835-44. 2006
    ....
  65. ncbi Sunitinib versus interferon alfa in metastatic renal-cell carcinoma
    Robert J Motzer
    Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    N Engl J Med 356:115-24. 2007
    ..Since sunitinib malate has shown activity in two uncontrolled studies in patients with metastatic renal-cell carcinoma, a comparison of the drug with interferon alfa in a phase 3 trial is warranted...
  66. ncbi Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics
    Cynthia X Ma
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Trends Mol Med 17:88-96. 2011
    ..In this review, we summarize recent advances and controversies in the development and application of CHK1 inhibitors as cancer therapeutics...
  67. ncbi Targeted cancer therapy
    Charles Sawyers
    Howard Hughes Medical Institute, David Geffen School of Medicine at UCLA, Jonsson Comprehensive Cancer Center, 10833 LeConte Avenue, Los Angeles, California 90095, USA
    Nature 432:294-7. 2004
    ..Recent progress in understanding the molecular changes that underlie cancer development offer the prospect of specifically targeting malfunctioning molecules and pathways to achieve more effective and rational cancer therapy...
  68. ncbi PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase
    Yasemin Sancak
    Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, MA 02142, USA
    Mol Cell 25:903-15. 2007
    ..We propose that the relative strengths of the rheb- and PRAS40-mediated inputs to mTORC1 set overall pathway activity and that insulin activates mTORC1 through the coordinated regulation of both...
  69. pmc EGFR-mutated lung cancer: a paradigm of molecular oncology
    Zhenfeng Zhang
    Division of Hematology Oncology, Herbert Irving Comprehensive Cancer Center, New York Presbyterian Hospital Columbia University Medical Center, New York, NY, USA
    Oncotarget 1:497-514. 2010
    ....
  70. ncbi Epithelial to mesenchymal transition is a determinant of sensitivity of non-small-cell lung carcinoma cell lines and xenografts to epidermal growth factor receptor inhibition
    Stuart Thomson
    Departments of Translational Research and Oncology Research, OSI Pharmaceuticals, Inc, Farmingdale, NY 11735, USA
    Cancer Res 65:9455-62. 2005
    ..These data suggest that EMT may be a general biological switch rendering non-small cell lung tumors sensitive or insensitive to EGFR inhibition...
  71. ncbi Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients
    Robert L Yauch
    Department of Molecular Diagnostics, Genentech, Inc, South San Francisco, California 94080, USA
    Clin Cancer Res 11:8686-98. 2005
    ..These data support a potential role for EMT as a determinant of EGFR activity in NSCLC tumor cells and E-cadherin expression as a novel biomarker predicting clinical activity of the EGFR inhibitor erlotinib in NSCLC patients...
  72. pmc PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer
    V Serra
    Experimental Therapeutics Program, Vall d Hebron Institute of Oncology, Barcelona, Spain
    Oncogene 30:2547-57. 2011
    ..Combined anti-MEK or anti-HER2 therapy with PI3K inhibitors may be required in order to achieve optimal efficacy in HER2-overexpressing breast cancer. This approach warrants clinical evaluation...
  73. pmc G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer
    N Bucher
    Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    Br J Cancer 98:523-8. 2008
    ....
  74. ncbi Role of tyrosine kinase inhibitors in cancer therapy
    Amit Arora
    University of Nebraska College of Medicine, Department of Pharmacology and Experimental Neuroscience, 985800 Nebraska Medical Center, Omaha, NE 68198 5800, USA
    J Pharmacol Exp Ther 315:971-9. 2005
    ..The availability of newer inhibitors and improved patient selection will help overcome these problems in the future...
  75. ncbi mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways
    Pradip K Majumder
    Department of Medical Oncology, Dana Farber Cancer Institute, and Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Med 10:594-601. 2004
    ....
  76. ncbi Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer
    Jeffrey A Engelman
    Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA
    Clin Cancer Res 14:2895-9. 2008
    ..Ongoing research efforts will likely continue to identify additional resistance mechanisms, and these findings will hopefully translate into effective therapies for non-small cell lung cancer patients...
  77. ncbi Sunitinib: from rational design to clinical efficacy
    Laura Q M Chow
    Department of Medical Oncology, University of Colorado Health Sciences Center, Aurora, CO 80045, USA
    J Clin Oncol 25:884-96. 2007
    ....
  78. ncbi The Aurora kinase family in cell division and cancer
    Gerben Vader
    Laboratory of Experimental Oncology, Department of Medical Oncology, University Medical Center Utrecht, Stratenum 2 125, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands
    Biochim Biophys Acta 1786:60-72. 2008
    ....
  79. pmc Chronic myeloid leukemia: mechanisms of blastic transformation
    Danilo Perrotti
    Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 41230, USA
    J Clin Invest 120:2254-64. 2010
    ..The latter responds poorly to treatment and is usually fatal. Here, we discuss what is known about the molecular mechanisms leading to blastic transformation of CML and propose some novel therapeutic approaches...
  80. pmc PTEN loss contributes to erlotinib resistance in EGFR-mutant lung cancer by activation of Akt and EGFR
    Martin L Sos
    Max Planck Institute for Neurological Research with Klaus Joachim Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Köln, Germany
    Cancer Res 69:3256-61. 2009
    ..These results suggest a novel resistance mechanism in EGFR-mutant NSCLC involving PTEN loss...
  81. pmc MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia
    Yana Pikman
    Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS Med 3:e270. 2006
    ....
  82. ncbi Tyrosine kinases as targets for cancer therapy
    Daniela S Krause
    Molecular Oncology Research Institute, Division of Hematology Oncology, Tufts New England Medical Center, Boston, MA 02111, USA
    N Engl J Med 353:172-87. 2005
  83. ncbi Cell cycle kinases as therapeutic targets for cancer
    Silvia Lapenna
    Oncology Research Centre of Mercogliano, Mercogliano, Avellino, Italy
    Nat Rev Drug Discov 8:547-66. 2009
    ..Here, we discuss the potential and limitations of established cell cycle kinases as targets in anticancer drug discovery as well as novel strategies for the design of new agents...
  84. pmc Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor
    Matthew R Janes
    Department of Molecular Biology and Biochemistry, Institute for Immunology, University of California Irvine, Irvine, California, USA
    Nat Med 16:205-13. 2010
    ..These findings establish that Ph(+) transformed cells are more sensitive than normal lymphocytes to selective TORC1/2 inhibitors and support the development of such inhibitors for leukemia therapy...
  85. ncbi Cell cycle, CDKs and cancer: a changing paradigm
    Marcos Malumbres
    Cell Division and Cancer Group, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncologicas CNIO, 28029 Madrid, Spain
    Nat Rev Cancer 9:153-66. 2009
    ..Emerging evidence suggests that tumour cells may also require specific interphase CDKs for proliferation. Thus, selective CDK inhibition may provide therapeutic benefit against certain human neoplasias...
  86. ncbi LTP inhibits LTD in the hippocampus via regulation of GSK3beta
    Stephane Peineau
    MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University Walk, Bristol, BS8 1TD, United Kingdom
    Neuron 53:703-17. 2007
    ..We conclude that the regulation of GSK3beta activity provides a powerful mechanism to preserve information encoded during LTP from erasure by subsequent LTD, perhaps thereby permitting the initial consolidation of learnt information...
  87. pmc Reversal of experimental pulmonary hypertension by PDGF inhibition
    Ralph Theo Schermuly
    Department of Internal Medicine, Justus Liebig University Giessen, Giessen, Germany
    J Clin Invest 115:2811-21. 2005
    ..This regimen offers a unique novel approach for antire-modeling therapy in progressed pulmonary hypertension...
  88. pmc PTEN and the PI3-kinase pathway in cancer
    Nader Chalhoub
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, TN 38105 2794, USA
    Annu Rev Pathol 4:127-50. 2009
    ..The significance and complexity of PI3K signaling make it an important but challenging therapeutic target for cancer...
  89. pmc Targeting the cancer kinome through polypharmacology
    Zachary A Knight
    Zachary A Knight is at The Rockefeller University, New York, New York 10065, USA
    Nat Rev Cancer 10:130-7. 2010
    ..If it is necessary to inhibit multiple kinases, how do we choose which ones? In this Opinion article, we discuss some of the strategies that are currently being used to identify new therapeutic combinations of kinase targets...
  90. ncbi AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer
    Stephen R Wedge
    Cancer Bioscience, AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom
    Cancer Res 65:4389-400. 2005
    ..AZD2171 is being developed clinically as a once-daily oral therapy for the treatment of cancer...
  91. ncbi Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway
    Hui Wen Lo
    Cancer Cell 7:575-89. 2005
    ..Our work suggests that the deregulated iNOS/NO pathway may partly contribute to the malignant biology of tumor cells with high levels of nuclear EGFR and STAT3...
  92. ncbi Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity
    Rakesh Kumar
    Oncology Biology, GlaxoSmithKline, 1250 South Collegeville Road, UP1450, Collegeville, PA 19426, USA
    Mol Cancer Ther 6:2012-21. 2007
    ..Furthermore, the steady-state concentration of pazopanib determined from preclinical activity showed a strong correlation with the pharmacodynamic effects and antitumor activity in the phase I clinical trial...
  93. pmc NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas
    Ta Jen Liu
    Department of Neuro Oncology, The University of Texas M D Anderson Cancer Center, Unit 431, 1515 Holcombe Boulevard, Houston, TX 77030
    Mol Cancer Ther 8:2204-10. 2009
    ..These results warrant further development of NVP-BEZ235 for clinical trials for human gliomas or other advanced cancers with altered PI3K/Akt/mTOR signaling...
  94. ncbi Imatinib mesylate treatment of nephrogenic systemic fibrosis
    Jonathan Kay
    Rheumatology Unit, Massachusetts General Hospital, Boston, MA 02114, USA
    Arthritis Rheum 58:2543-8. 2008
    ..To examine the effectiveness of imatinib mesylate in the treatment of nephrogenic systemic fibrosis (NSF)...
  95. pmc Acquired resistance to epidermal growth factor receptor kinase inhibitors associated with a novel T854A mutation in a patient with EGFR-mutant lung adenocarcinoma
    James Bean
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Clin Cancer Res 14:7519-25. 2008
    ..We aimed to identify additional second-site alterations associated with acquired resistance...
  96. ncbi TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
    Ken Inoki
    Department of Biological Chemistry, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109, USA
    Nat Cell Biol 4:648-57. 2002
    ..Our data indicate a molecular mechanism for TSC2 in insulin signalling, tumour suppressor functions and in the inhibition of cell growth...
  97. ncbi Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib
    David Marin
    Department of Haematology, Imperial College London, Hammersmith Hospital, Du Cane Rd, London W12 0NN, United Kingdom
    J Clin Oncol 28:2381-8. 2010
    ..There is a considerable variability in the level of molecular responses achieved with imatinib therapy in patients with chronic myeloid leukemia (CML). These differences could result from variable therapy adherence...
  98. pmc Drugging the PI3 kinome: from chemical tools to drugs in the clinic
    Paul Workman
    Cancer Research UK Centre for Cancer Therapeutics, Section of Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, United Kingdom
    Cancer Res 70:2146-57. 2010
    ..The challenges and outlook for drugging the PI3 kinome are discussed in the more general context of the role of structural biology and chemical biology in innovative drug discovery...
  99. pmc Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma
    Clara Montagut
    Center for Molecular Therapeutics, Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts, USA
    Cancer Res 68:4853-61. 2008
    ..Geldanamycin effectively promotes the degradation of CRAF, thereby revealing a potential therapeutic strategy to overcome resistance to RAF inhibition in a subset of BRAF mutant tumors...
  100. pmc Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition
    Olga K Mirzoeva
    Department of Medicine, Division of Gastroenterology, University of California, San Francisco, California 94115, USA
    Cancer Res 69:565-72. 2009
    ....
  101. 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...

Research Grants62

  1. Right ventricular contractile dysfunction after pressure overload
    CLIFFORD RUSSELL GREYSON; Fiscal Year: 2013
    ..Specific Aim 4: Determine whether protease or protein kinase inhibitors currently in clinical trials can attenuate right heart failure in acute RV pressure overload...
  2. Molecular Basis of Pathogenicity of IgA1-containing Immune Complexes
    Jan Novak; Fiscal Year: 2013
    ..Relevance: The results will shed light on the pathogenesis of IgAN and identify therapeutic targets for disease-specific treatment of IgAN as well as potential response/prognostic biomarkers. ..
  3. Molecular Basis of Pathogenicity of IgA1-containing Immune Complexes
    Jan Novak; Fiscal Year: 2012
    ..Relevance: The improved understanding of the pathogenesis of IgAN will identify therapeutic targets for disease-specific therapy of IgAN as well as potential prognostic biomarkers. ..
  4. Protein kinase inhibitors that promote RGC survival and function
    Donald J Zack; Fiscal Year: 2010
    ..We also propose to explore the mechanisms by which these molecules work, with the hope that this will contribute to the development of new treatment strategies for glaucoma and other optic nerve diseases. ..
  5. Novel Neutrophil Autoantigens in Systemic Lupus Erythematosus
    Kaihong Su; Fiscal Year: 2013
    ..through the classical Fc3 receptor pathway and further dissect their signaling pathways using different protein kinase inhibitors. We will also determine the specific signaling of S4Ab2 and S4Ab4 antibodies upon binding to their ..
  6. Protein Kinases of a Trypanosome
    Kojo Mensa Wilmot; Fiscal Year: 2010
    ..brucei infection. In Specific Aim 2, we will validate the target of the protein kinase inhibitors, using a combination of affinity chromatography/chemical proteomics and molecular genetics approaches...
  7. Developing Selective EphA2 Inhibitors for the treatment of Cancer
    NATHANAEL SCHIANDER GRAY; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The dramatic anti-cancer activity of protein kinase inhibitors that target specific driver-mutations such as Bcr- Abl, EML4-ALK, mutant EGFR and V600E b-raf is revolutionizing cancer drug discovery...
  8. Mechanisms of LRRK2 Mediated Neurotoxicity
    Andrew B West; Fiscal Year: 2013
    ..Since small molecule protein kinase inhibitors have made an impact on the treatment of multiple types of cancer, LRRK2 represents a potential ..
  9. Development of HTS assay and screening paradigm to discover new kinase inhibitors
    David C Swinney; Fiscal Year: 2013
    ..The overall objective of the project is to provide a HTS screening assay and paradigm to identify protein kinase inhibitors for Trypanosoma brucei that causes Human African trypanosomiasis (HAT), or sleeping sickness...
  10. Studying how a general allosteric site regulates protein kinase function
    TERRY JUSTIN RETTENMAIER; Fiscal Year: 2013
    ..In the clinic, protein kinase inhibitors have ushered in the era of personalized medicine by transforming the standard of care for a variety of ..
  11. New Directions in Small Molecule Drug Discovery - Greenlee, Chair
    Andrew D Robertson; Fiscal Year: 2010
    ..in the discovery of therapeutics for the treatment of HCV infection (protease inhibitors) and cancer (protein kinase inhibitors)...
  12. Phosphorylation Biosensors for Drug Discovery
    Hung Teh Kao; Fiscal Year: 2013
    ..The objective of this application is to optimize our novel cell-based platform to respond to protein kinase inhibitors. The working hypothesis is that PhosFluor" can easily be engineered to fluoresce in response to other ..
  13. Motor Proteins in Brain Development
    RICHARD BERT VALLEE; Fiscal Year: 2013
    ..and cell fate;and to determine the mechanisms for cell cycle control of INM using small molecule protein kinase inhibitors and other reagents...
  14. OPIOID EFFECTS ON HYPOTHALAMIC NEURONAL EXCITABILITY
    Martin Kelly; Fiscal Year: 2002
    ..a) changes in mu-opioid agonist potency in females treated with morphine using membrane permeable protein kinase inhibitors; (b) the time course of morphine actions; and (c) the effects of morphine on the coupling of the ..
  15. Pathogenesis of Lyme Borreliosis in the Rhesus Monkey
    MARIO PHILIPP; Fiscal Year: 2007
    ..burgdorferi and lipoprotein in inflammation and neurodegeneration, specifically, the expression and involvement of pertinent TLR in mediating cytokine production and apoptosis in the different cell combinations. ..
  16. Complementation assay for protein kinase inhibitors
    RICHARD EGLEN; Fiscal Year: 2002
    ..The market for these assays will be in the millions of dollars. ..
  17. DOPAMINE/GLUTAMATE INTERACTIONS IN NUCLEUS ACCUMBENS
    MARINA WOLF; Fiscal Year: 2001
    ..The identity of the residue phosphorylated, combined with experiments involving selective protein kinase inhibitors, will help identify the kinases involved in DA receptor-mediated effects.
  18. PROTEOMIC ANALYSIS OF OSTEOCYTES
    Norman Karin; Fiscal Year: 2009
    ..also include transwell assays for the quantitation of MLO-Y4 cell dendritogenesis, and the inclusion of protein kinase inhibitors to verify the role of specific phosphorylation events in LPA-induced dendrite outgrowth...
  19. REGULATION OF THE SQUID AXON NA, K, C1 COTRANSPORTER
    John Russell; Fiscal Year: 2003
    ..To date, we have not identified any other types of protein kinase inhibitors capable of inhibiting the squid NKCC...
  20. Development of Superagonist Analogs of Recombinant Human TSH for Imaging and Ther
    Bruce Weintraub; Fiscal Year: 2009
    ..of the diagnostic and therapeutic effects of TR1401 and 1402 with those of selected newly developed protein kinase inhibitors in vitro and in vivo...
  21. Macrophages and dopamine: a role in NeuroAIDS
    Peter Gaskill; Fiscal Year: 2009
    ..Experiments will also use protein kinase inhibitors during HIV infection to examine the signaling pathways involved in dopamine enhanced HIV replication...
  22. MOLECULAR MECHANISMS REGULATING THE PROTEIN KINASE SPRK
    Kathleen Gallo; Fiscal Year: 2002
    ..Understanding how protein kinases are regulated in both normal and cancer cells opens the door to the development of new protein-kinase inhibitors (or inhibitors) that may serve as useful therapeutics. ..
  23. PROTEIN KINASE INHIBITORS
    David Hangauer; Fiscal Year: 1993
    ..inhibitor designs to prepare prototype anti-cancer, anti-AIDS, immunosuppressant and anti-hypertensive protein kinase inhibitors which may be used as lead compounds for a more extensive research program aimed at developing clinically ..
  24. Computer-aided Design of Anti-cancer Drugs Targeting Protein Kinases
    Chung Wong; Fiscal Year: 2006
    ..extends our previous informatics/structural modeling approach to help guide the development of selective protein kinase inhibitors that have fewer side effects...
  25. HUMAN MULTIDRUG RESISTANCE (P GLYCOPROTEIN) GENES
    IGOR RONINSON; Fiscal Year: 1999
    ..induce MDR1 expression in different types of human cells, and that such induction can be prevented with protein kinase inhibitors. The regulatory mechanisms of this potentially clinically relevant phenomenon will be analyzed, and ..
  26. ROLE OF C-AMP IN RENIN RELEASE
    WINFRED MAGEE; Fiscal Year: 1990
    ..prostaglandin I2, isoproterenol, 9-substituted adenosine derivatives, phosphodiesterase inhibitors, protein kinase inhibitors) will be used to test our hypothesis...
  27. CELLULAR REGULATION OF TYROSINE HYDROXYLASE
    John Haycock; Fiscal Year: 1991
    ..In addition, the effects of injecting purified protein kinases and protein kinase inhibitors directly into chromaffin cells will be evaluated for effects upon tyrosine hydroxylase phosphorylation ..
  28. Computational and experimental studies of targets of protein kinase inhibitors
    ADRIAN HAMILTON ELCOCK; Fiscal Year: 2010
    ..The research proposed here directly addresses the single greatest challenge to the therapeutic pursuit of kinases: how to design small molecule inhibitors that can specifically inhibit a kinase of interest. ..
  29. Kinase Inhibitors against Neurodegeneration
    Gary Lynch; Fiscal Year: 2004
    ..place in NPC1-/- mice? Therefore, our specific aims are to (i) determine the effects of a variety of protein kinase inhibitors on a well established in vitro model of tau hyperphosphorylation and NFT formation using cultured ..
  30. Role of Central CRH in Stress-Induced Behavior
    Ned Kalin; Fiscal Year: 2006
    ..Additionally, using specific protein kinase inhibitors, we will determine which protein kinases are involved in mediating the acute behavioral effects of CRH...
  31. Novel assay to identify non-ATP competitive protein kinase inhibitors
    Mark Nowak; Fiscal Year: 2007
    ..We propose to develop a novel high throughput screening assay to identify non-ATP competitive protein kinase inhibitors with potentially better selectivity and safety profiles...
  32. REGULATION OF TRANSPORT IN MAMMALIAN CELLS
    EUGENE BARNES; Fiscal Year: 1993
    ..The specific aims are: 1) To examine the effects of cAMP derivatives and protein kinase inhibitors on the responses of cortical neurons to GABA...
  33. Obliquely deposited substrates for detection of Ras
    Barbara Israel; Fiscal Year: 2003
    ..The movement of protein kinase inhibitors and related compounds into clinical trials will increase the demand for such assays in academic, ..
  34. NOVEL ASSAY PLATFORM FOR ASESSING PROTEIN KINASE INHIBITORS
    Val Golovlev; Fiscal Year: 2009
    ..The technology under development in this SBIR project has a unique capability for identification and study allosteric kinase inhibitors and is able to provide more information quickly and at a lower cost. ..
  35. Proliferation Control of Neuroendo/Renal Organogenesis
    Xue Li; Fiscal Year: 2005
    ..proliferation by directly regulating key components of cell cycle machinery, such as cyclin-dependent protein kinase inhibitors. Functional importance of Six-family genes in tumorigenesis is further suggested by the observations ..
  36. MODULATION GIRK CHANNELS--ALPHA SUBUNITS OF G PROTEINS
    Nathan Dascal; Fiscal Year: 1999
    ..by neurotransmitters that activate G-q, and the process of GIRK desensitization, by examining effects of protein kinase inhibitors and purified protein kinases in Xenopus oocytes, and by mutating putative phosphorylation sites in ..
  37. Development of Conformation Specific Kinase Inhibitors
    John Prescott; Fiscal Year: 2003
    ..Once optimized, this approach will be applicable to the development of a large number of protein kinase inhibitors with significant anti-cancer therapeutic value.
  38. 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]..
  39. Highly Selective, Irreversible Protein Kinase Inhibitors
    Jack Taunton; Fiscal Year: 2008
    ..abstract_text> ..
  40. Phase I Clinical Trials of Anti-Cancer Agents
    Francis Giles; Fiscal Year: 2007
    ..abstract_text> ..
  41. Phase II Study of Imatinib Mesylate in Patients with Inoperable Melanoma
    Gary K Schwartz; Fiscal Year: 2010
    ..Dose reductions are allowed in the setting of toxicity. Imaging studies will be performed on an every 6 week schedule. ..
  42. CLINICAL TRIALS AND MENTORING IN ONCOLOGY RESEARCH
    Robert Motzer; Fiscal Year: 2003
    ..One recently joined staff at MSKCC in the Genito-urinary Section. Mentoring of clinical trials is extended beyond fellowship to junior faculty members. ..
  43. 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. ..
  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. 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. ..
  46. CLINICAL TRIALS OF FLAVOPIRIDOL WITH CHEMOTHERAPY
    Gary Schwartz; Fiscal Year: 2008
    ..Continue to examine the mechanisms by which flavopiridol potentiates CPT-11 induced apoptosis, which should provide the opportunity to identify new biomarkers of response for these flavopiridol drug combinations. ..
  47. DEVELOPMENT OF MATURE ZEBRAFISH AS AN ANIMAL MODEL
    Evan Keller; Fiscal Year: 2006
    ....
  48. Inhibition of nf-kb signaling in melanoma therapy
    Jeffrey Sosman; Fiscal Year: 2005
    ..Abstract Not Provided ..
  49. New Organosulfur Anticarcinogenic Enzyme Inducers
    MARK WELKER; Fiscal Year: 2005
    ..Therefore, study of these reactions will illuminate which structural elements to include in the preparation of more potent enzyme inducers. ..
  50. Clinical Activity of 17-AAG in Lymphoma
    Anas Younes; Fiscal Year: 2007
    ..In Aim 3 we will correlate the biologic effects of 17-AAG and clinical response in patients with relapsed MCL, ALCL, and HL. [unreadable] [unreadable] [unreadable]..
  51. REGULATION OF PERIPHERAL INFLAMMATION BY THE CNS
    Gary Firestein; Fiscal Year: 2002
    ..These studies will provide a basis for understanding the central nervous system-immune system connection as well as explore novel therapeutic targets. ..
  52. Biochemical screen for protein ligation
    Michael Mattern; Fiscal Year: 2007
    ..In Phase II, compound collections will be screened using this assay, with the aim of finding compounds that have the potential to lead to drugs. [unreadable] [unreadable] [unreadable]..
  53. Hypertrophy, Heart Failure and PKC
    Daria Mochly Rosen; Fiscal Year: 2008
    ..Together, these studies will identify the PKC isozyme(s) that should be targeted for the development of new therapeutics for human heart failure, especially if PKC-based pharmacotherapy is considered ..
  54. UW Stipends for Training Aspiring Researchers (STAR)
    Michael Portman; Fiscal Year: 2008
    ..increasing the numbers of underrepresented minority investigators involved in heart, lung, blood, and sleep disorder research. ..
  55. Osteoporosis Screen for Praja1 E3 Ligase Inhibitors
    Michael Mattern; Fiscal Year: 2008
    ..The latter have been good sources of highly effective drugs in the past (taxol, statins, etc). [unreadable] [unreadable] [unreadable] [unreadable]..
  56. ETHANOL EFFECTS ON GLYCINE RECEPTOR/CHANNEL FUNCTION
    Jiang Hong Ye; Fiscal Year: 2003
    ....
  57. The Renin-Angiotensin System in Hepatitis and Hepatoma
    Mary Maluccio; Fiscal Year: 2008
    ..The preclinical model involves a human hepatitis derived hepatocellular carcinoma xenograft into an immunodeficient mouse. [unreadable] [unreadable] [unreadable]..
  58. INHIBITION OF HIV GENE TRANSCRIPTION BY SMALL MOLECULES
    JOEL GOTTESFELD; Fiscal Year: 2004
    ..Given our success in inhibition of virus replication in cell culture, we propose collaborative preclinical studies with the Mosier laboratory to determine the effectiveness of polyamides in the human PBL-SCID mouse model. ..
  59. Novel, P. jirovecii Specific Antipneumocystis Agents
    Aleem Gangjee; Fiscal Year: 2009
    ..These agents could be used alone or in combination to treat PCP thus providing novel agents against a new target. ..
  60. Antitumor Antimitotics That Reverse Tumor Resistance
    Aleem Gangjee; Fiscal Year: 2010
    ..The study will also further define the mechanism of action of the novel series and could afford agents for clinical use. ..
  61. PHARMACOLOGY OF ANTICANCER DRUGS IN ADVANCED AGE
    HEINZ LENZ; Fiscal Year: 2003
    ....