indoles

Summary

Top Publications

  1. pmc Inhibition of mutated, activated BRAF in metastatic melanoma
    Keith T Flaherty
    Abramson Cancer Center of the University of Pennsylvania, Philadelphia, USA
    N Engl J Med 363:809-19. 2010
  2. 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
  3. pmc RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
    Poulikos I Poulikakos
    Department of Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 480:387-90. 2011
  4. pmc Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma
    Robert J Motzer
    Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    J Clin Oncol 27:3584-90. 2009
  5. 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
  6. ncbi Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
    Alexei Degterev
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Chem Biol 1:112-9. 2005
  7. 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
  8. pmc Glucosinolate metabolites required for an Arabidopsis innate immune response
    Nicole K Clay
    Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 323:95-101. 2009
  9. 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
  10. pmc Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3
    Michael Martin
    Department of Oral Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294 2170, USA
    Nat Immunol 6:777-84. 2005

Detail Information

Publications306 found, 100 shown here

  1. pmc Inhibition of mutated, activated BRAF in metastatic melanoma
    Keith T Flaherty
    Abramson Cancer Center of the University of Pennsylvania, Philadelphia, USA
    N Engl J Med 363:809-19. 2010
    ..The identification of somatic mutations in the gene encoding the serine-threonine protein kinase B-RAF (BRAF) in the majority of melanomas offers an opportunity to test oncogene-targeted therapy for this disease...
  2. 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
    ....
  3. pmc RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
    Poulikos I Poulikakos
    Department of Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Nature 480:387-90. 2011
    ....
  4. pmc Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma
    Robert J Motzer
    Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    J Clin Oncol 27:3584-90. 2009
    ..Final survival analyses and updated results are reported...
  5. 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
    ....
  6. ncbi Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
    Alexei Degterev
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Chem Biol 1:112-9. 2005
    ..Our study identifies a previously undescribed basic cell-death pathway with potentially broad relevance to human pathologies...
  7. 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...
  8. pmc Glucosinolate metabolites required for an Arabidopsis innate immune response
    Nicole K Clay
    Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 323:95-101. 2009
    ..Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens...
  9. 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...
  10. pmc Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3
    Michael Martin
    Department of Oral Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294 2170, USA
    Nat Immunol 6:777-84. 2005
    ..These findings demonstrate a regulatory function for GSK3 in modulating the inflammatory response...
  11. 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...
  12. pmc PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression
    Kim H T Paraiso
    Department of Molecular Oncology, The Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, Florida, USA
    Cancer Res 71:2750-60. 2011
    ..In conclusion, we have shown for the first time that loss of PTEN contributes to intrinsic BRAF inhibitor resistance via the suppression of BIM-mediated apoptosis...
  13. pmc Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance
    Hubing Shi
    Division of Dermatology, Department of Medicine, University of California, Los Angeles, 52 121 CHS, 10833 Le Conte Avenue, California 90095 1750, USA
    Nat Commun 3:724. 2012
    ..Thus, alternative clinical strategies may potentially overcome distinct modes of extracellular signal-regulated kinase reactivation underlying acquired B-RAF inhibitor resistance in melanoma...
  14. pmc Bacterial charity work leads to population-wide resistance
    Henry H Lee
    Howard Hughes Medical Institute, Center for BioDynamics, Boston, Massachusetts 02115, USA
    Nature 467:82-5. 2010
    ....
  15. ncbi Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor
    Noboru Sato
    Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Nat Med 10:55-63. 2004
    ..These results suggest that the use of GSK-3-specific inhibitors such as BIO may have practical applications in regenerative medicine...
  16. 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
    ....
  17. ncbi Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study
    Daniel Y C Heng
    FRCPC, Department of Medical Oncology, Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada
    J Clin Oncol 27:5794-9. 2009
    ..There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy...
  18. pmc EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib
    Ryan B Corcoran
    Massachusetts General Hospital Cancer Center, Boston, MA 02129, USA
    Cancer Discov 2:227-35. 2012
    ..These findings support evaluation of combined RAF and EGFR inhibition in BRAF mutant CRC patients...
  19. pmc RAS mutations are associated with the development of cutaneous squamous cell tumors in patients treated with RAF inhibitors
    Patrick A Oberholzer
    Broad Institute of Massachusetts Institute of Technology, Cambridge, USA
    J Clin Oncol 30:316-21. 2012
    ..The potential of these agents to promote secondary malignancies is concerning. We analyzed cSCC and KA lesions for genetic mutations in an attempt to identify an underlying mechanism for their formation...
  20. 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...
  21. ncbi Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription
    M P Coghlan
    Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Essex, UK
    Chem Biol 7:793-803. 2000
    ..This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3...
  22. pmc The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner
    Eric W Joseph
    Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:14903-8. 2010
    ..This selectivity may lead to a broader therapeutic index and help explain the greater antitumor activity observed with this drug than with MEK inhibitors...
  23. ncbi Functional expression and mutations of c-Met and its therapeutic inhibition with SU11274 and small interfering RNA in non-small cell lung cancer
    Patrick C Ma
    Section of Hematology Oncology, Department of Medicine, University of Chicago Medical Center, Pritzker School of Medicine, Chicago, Illinois, USA
    Cancer Res 65:1479-88. 2005
    ..These results indicate that c-Met inhibition will be an important therapeutic strategy against NSCLC to improve its clinical outcome...
  24. ncbi Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines
    Rudiger Hardeland
    Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Gottingen, D 37073 Gottingen, Germany
    J Pineal Res 47:109-26. 2009
    ..AMK easily interacts with aromates, forms adducts with tyrosyl and tryptophanyl residues, and may modify proteins...
  25. ncbi Clinical studies of histone deacetylase inhibitors
    H Miles Prince
    Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Australia and University of Melbourne, Parkville, Victoria, Australia
    Clin Cancer Res 15:3958-69. 2009
    ..The use of the biomarker of histone hyperacetylation has been useful as a guide to target specificity, but generally does not predict for response and the search for more clinically relevant biomarkers must continue...
  26. ncbi KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel
    H S Wang
    Institute of Molecular Cardiology, Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, NY 11794, USA
    Science 282:1890-3. 1998
    ..The biophysical properties, sensitivity to pharmacological blockade, and expression pattern of the KCNQ2 and KCNQ3 potassium channels were determined. It is concluded that both these subunits contribute to the native M-current...
  27. pmc The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms
    Kim H T Paraiso
    The Department of Molecular Oncology, The Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
    Clin Cancer Res 18:2502-14. 2012
    ..The clinical use of BRAF inhibitors is being hampered by the acquisition of drug resistance. This study shows the potential therapeutic use of the HSP90 inhibitor (XL888) in six different models of vemurafenib resistance...
  28. pmc Efficacy, safety, and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: a phase II study
    Andrew X Zhu
    Division of Hematology Oncology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA
    J Clin Oncol 27:3027-35. 2009
    ..To assess the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) and explore biomarkers for sunitinib response...
  29. pmc Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma
    Gideon Bollag
    Plexxikon Inc, 91 Bolivar Drive, Berkeley, California 94710, USA
    Nature 467:596-9. 2010
    ..These data demonstrate that BRAF-mutant melanomas are highly dependent on B-RAF kinase activity...
  30. pmc Interleukin-8 mediates resistance to antiangiogenic agent sunitinib in renal cell carcinoma
    Dan Huang
    Laboratory of Cancer Genetics, Laboratory of Computational Biology, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
    Cancer Res 70:1063-71. 2010
    ..Our results reveal IL-8 as an important contributor to sunitinib resistance in ccRCC and a candidate therapeutic target to reverse acquired or intrinsic resistance to sunitinib in this malignancy...
  31. ncbi In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship
    Dirk B Mendel
    Preclinical Research and Exploratory Development, SUGEN, Inc, South San Francisco, California 94080, USA
    Clin Cancer Res 9:327-37. 2003
    ..The pharmacokinetic/pharmacodynamic relationship established for SU11248 in these preclinical studies has aided in the design, selection, and evaluation of dosing regimens being tested in human trials...
  32. ncbi Novel gp91(phox) homologues in vascular smooth muscle cells : nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways
    B Lassegue
    Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA, USA
    Circ Res 88:888-94. 2001
    ..These data support a role for nox1 in redox signaling in VSMCs and provide insight into the molecular identity of the VSMC NAD(P)H oxidase and its potentially critical role in vascular disease...
  33. pmc Combinatorial treatments that overcome PDGFRβ-driven resistance of melanoma cells to V600EB-RAF inhibition
    Hubing Shi
    Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
    Cancer Res 71:5067-74. 2011
    ..Together, our findings offer a rational strategy to guide clinical testing in preidentified subsets of patients who relapse during treatment with (V600E)B-RAF inhibitors...
  34. ncbi SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types
    T A Fong
    SUGEN, Inc, South San Francisco, California 94080, USA
    Cancer Res 59:99-106. 1999
    ..These findings support that pharmacological inhibition of the enzymatic activity of the vascular endothelial growth factor receptor represents a novel strategy for limiting the growth of a wide variety of tumor types...
  35. ncbi Activation of MAPK kinase 9 induces ethylene and camalexin biosynthesis and enhances sensitivity to salt stress in Arabidopsis
    Juan Xu
    State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing 100094, China
    J Biol Chem 283:26996-7006. 2008
    ..The results reported here reveal that the MKK9-MPK3/MPK6 cascade participates in the regulation of the biosynthesis of ethylene and camalexin and may be an important axis in the stress responses of Arabidopsis...
  36. ncbi Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial
    George D Demetri
    Ludwig Center at Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Lancet 368:1329-38. 2006
    ....
  37. pmc Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032
    Jill C Rubinstein
    Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA
    J Transl Med 8:67. 2010
    ..Here we present evidence that a patient bearing the BRAF V600K mutation responded remarkably to PLX4032, suggesting that clinical trials should include all patients with activating BRAF V600E/K mutations...
  38. ncbi Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma
    Brian I Rini
    Department of Solid Tumor Oncology and Urology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Avenue, Desk R35, Cleveland, OH 44195, USA
    J Clin Oncol 26:3743-8. 2008
    ..To assess the safety and efficacy of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma (mRCC) and explore biomarkers for sunitinib response...
  39. 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
    ....
  40. ncbi Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations
    James G Greger
    Oncology R and D Translational Research, GlaxoSmithKline, Collegeville, Pennsylvania, USA
    Mol Cancer Ther 11:909-20. 2012
    ..In addition, these resistant clones respond to the combination of GSK2126458 with GSK2118436 or GSK1120212. Clinical trials are ongoing or planned to test these combinations...
  41. ncbi Analytical performance of a real-time PCR-based assay for V600 mutations in the BRAF gene, used as the companion diagnostic test for the novel BRAF inhibitor vemurafenib in metastatic melanoma
    Harkanwal Halait
    Roche Molecular Diagnostics, Pleasanton, CA 94588, USA
    Diagn Mol Pathol 21:1-8. 2012
    ..A simple 1:2 dilution resulted in a valid test result of 76% in such cases. The cobas test is a reproducible assay that detects some non-V600E mutations and is more accurate than direct sequencing in detecting BRAFV600E...
  42. pmc Single-dose intravenous toxicity study of IRDye 800CW in Sprague-Dawley rats
    Milton V Marshall
    Baylor College of Medicine, Houston, TX, USA
    Mol Imaging Biol 12:583-94. 2010
    ..Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. To prepare for clinical use as a near-infrared fluorophore, a toxicity study was conducted on IRDye 800CW carboxylate...
  43. ncbi Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium
    D Z Chen
    North Shore-Long Island Jewish Research Institute, Manhasset, NY 11030, USA
    J Nutr 131:3294-302. 2001
    ....
  44. ncbi RG7204 (PLX4032), a selective BRAFV600E inhibitor, displays potent antitumor activity in preclinical melanoma models
    Hong Yang
    Discovery Oncology, Hoffmann La Roche, Inc, Nutley, New Jersey, USA
    Cancer Res 70:5518-27. 2010
    ..There was no toxicity observed in any dose group in any of the in vivo models tested. Our findings offer evidence of the potent antitumor activity of RG7204 against melanomas harboring the mutant BRAF(V600E) gene...
  45. ncbi An overview of small-molecule inhibitors of VEGFR signaling
    S Percy Ivy
    Investigational Drug Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA
    Nat Rev Clin Oncol 6:569-79. 2009
    ..The on-target effects seem to be mechanistically based and predicted by VEGFR inhibition. Small-molecule inhibitors of angiogenesis are active in a wide variety of malignancies and fill a unique niche for cancer therapeutics...
  46. pmc Reversing melanoma cross-resistance to BRAF and MEK inhibitors by co-targeting the AKT/mTOR pathway
    Mohammad Atefi
    Department of Medicine, Division of Hematology Oncology, University of California Los Angeles, Los Angeles, California, United States of America
    PLoS ONE 6:e28973. 2011
    ..Clinical trials are in progress using MEK inhibitors following disease progression in patients receiving BRAF inhibitors. However, the PI3K/AKT pathway can also induce resistance to the inhibitors of MAPK pathway...
  47. ncbi Single nucleotide polymorphism associations with response and toxic effects in patients with advanced renal-cell carcinoma treated with first-line sunitinib: a multicentre, observational, prospective study
    Jesus Garcia-Donas
    Hospital Universitario Fundacion Alcorcon, Alcorcon, Spain
    Lancet Oncol 12:1143-50. 2011
    ..Because there are no validated molecular predictors of response or toxicity to sunitinib, we aimed to identify genetic markers predictive of outcome and toxic effects...
  48. pmc Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752
    Gromoslaw A Smolen
    Cancer Center and Department of Pathology, Molecular Pathology Research Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 103:2316-21. 2006
    ..MET amplification may thus identify a subset of epithelial cancers that are uniquely sensitive to disruption of this pathway and define a patient group that is appropriate for clinical trials of targeted therapy using MET inhibitors...
  49. pmc Hypertension as a biomarker of efficacy in patients with metastatic renal cell carcinoma treated with sunitinib
    Brian I Rini
    Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH 44195, USA
    J Natl Cancer Inst 103:763-73. 2011
    ..We evaluated the association of sunitinib-induced HTN with antitumor efficacy and HTN-associated adverse events in patients with metastatic renal cell carcinoma...
  50. ncbi Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases
    Panagiotis Polychronopoulos
    Laboratory of Pharmacognosy and Laboratory of Pharmaceutical Chemistry, Department of Pharmacy, University of Athens, Panepistimiopolis Zografou, GR 15771 Athens, Greece
    J Med Chem 47:935-46. 2004
    ..Indirubins, a family of bis-indoles isolated from various natural sources, are potent inhibitors of several kinases, including GSK-3...
  51. ncbi Indole as an intercellular signal in microbial communities
    Jin Hyung Lee
    School of Display and Chemical Engineering, Yeungnam University, Gyeongsan, Korea
    FEMS Microbiol Rev 34:426-44. 2010
    ..It appears indole plays an important role in bacterial physiology, ecological balance, and possibly human health. Here we discuss our current knowledge and perspectives on indole signaling...
  52. ncbi Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases
    Bodo Brueckner
    Division of Epigenetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    Cancer Res 65:6305-11. 2005
    ..These results establish RG108 as a DNA methyltransferase inhibitor with fundamentally novel characteristics that will be particularly useful for the experimental modulation of epigenetic gene regulation...
  53. ncbi MEK-independent survival of B-RAFV600E melanoma cells selected for resistance to apoptosis induced by the RAF inhibitor PLX4720
    Chen Chen Jiang
    Immunology and Oncology Unit, Newcastle, New South Wales, Australia
    Clin Cancer Res 17:721-30. 2011
    ..To examine mechanisms that determine long-term responses of B-RAF(V600E) melanoma cells to B-RAF inhibitors...
  54. pmc Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor
    Michael C Heinrich
    Division of Hematology Oncology, Department of Medicine and Cell and Developmental Biology, Portland Veterans Affairs Medical Center and Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    J Clin Oncol 26:5352-9. 2008
    ..We evaluated the impact of primary and secondary kinase genotype on sunitinib activity...
  55. pmc The Arabidopsis YUCCA1 flavin monooxygenase functions in the indole-3-pyruvic acid branch of auxin biosynthesis
    Anna N Stepanova
    Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA
    Plant Cell 23:3961-73. 2011
    ....
  56. ncbi Motesanib diphosphate in progressive differentiated thyroid cancer
    Steven I Sherman
    Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M D Anderson Cancer Center, Houston 77230 1402, USA
    N Engl J Med 359:31-42. 2008
    ..Motesanib diphosphate (AMG 706) is a novel oral inhibitor of VEGF receptors, platelet-derived growth-factor receptor, and KIT...
  57. ncbi Molecular pathobiology of gastrointestinal stromal sarcomas
    Christopher L Corless
    Department of Pathology, Oregon Health and Science University Cancer Institute, Portland, OR 97239, USA
    Annu Rev Pathol 3:557-86. 2008
    ....
  58. ncbi BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy
    Frank Hilberg
    Boehringer Ingelheim Austria GmbH, Vienna, Austria and Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany
    Cancer Res 68:4774-82. 2008
    ..These distinctive pharmacokinetic and pharmacodynamic properties may help explain clinical observations with BIBF 1120, currently entering phase III clinical development...
  59. ncbi Safety and efficacy of combining sunitinib with bevacizumab + paclitaxel/carboplatin in non-small cell lung cancer
    Mark A Socinski
    Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA
    J Thorac Oncol 5:354-60. 2010
    ....
  60. pmc Mechanisms of resistance to RAF inhibitors in melanoma
    Andrew E Aplin
    Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Invest Dermatol 131:1817-20. 2011
    ..Bi-directional translational efforts are now essential to determine the mechanisms underlying acquired/secondary and intrinsic resistance to RAF inhibitors...
  61. pmc PLX4032, a selective BRAF(V600E) kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAF melanoma cells
    Ruth Halaban
    Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA
    Pigment Cell Melanoma Res 23:190-200. 2010
    ..The results suggest that the drug can confer an advantage to BRAF(WT) primary and metastatic tumor cells in vivo and provide markers for monitoring clinical responses...
  62. ncbi Phase II study of sunitinib as first-line treatment of urothelial cancer patients ineligible to receive cisplatin-based chemotherapy: baseline interleukin-8 and tumor contrast enhancement as potential predictive factors of activity
    J Bellmunt
    Medical Oncology Service, University Hospital del Mar, Barcelona, Spain
    Ann Oncol 22:2646-53. 2011
    ..This trial was designed to assess the activity of sunitinib as first-line treatment in patients with metastatic urothelial cancer ineligible for cisplatin and to explore molecular and imaging variables predictive of clinical benefit...
  63. pmc Phase III randomized trial of sunitinib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer
    Carlos H Barrios
    PUCRS School of Medicine, Centro de Pesquisa em Oncologia, Jardim Botanico, Porto Alegre, RS, 90610 000, Brazil
    Breast Cancer Res Treat 121:121-31. 2010
    ..51%). The relative dose intensity was lower with sunitinib than capecitabine (73 vs. 95%). Based on these efficacy and safety results, sunitinib should not be used as monotherapy for patients with ABC...
  64. ncbi Development and characterization of clinically relevant tumor models from patients with renal cell carcinoma
    Jose A Karam
    Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
    Eur Urol 59:619-28. 2011
    ..Animal models are instrumental in understanding disease pathophysiology and mechanisms of therapy action and resistance in vivo...
  65. pmc Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells
    Hong Xin
    Divisions of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California, USA
    Cancer Res 69:2506-13. 2009
    ..These results suggest that Stat3 activity is important for RCC response to sunitinib, and Stat3 inhibition permits the direct proapoptotic activity of sunitinib on tumor cells and positive effects on tumor immunologic microenvironment...
  66. ncbi Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure
    S George
    Center for Sarcoma and Bone Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Eur J Cancer 45:1959-68. 2009
    ....
  67. ncbi The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies
    Junko Ozao-Choy
    Departments of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York, USA
    Cancer Res 69:2514-22. 2009
    ..These data suggest that sunitinib can be used to reverse immune suppression and as a potentially useful adjunct for enhancing the efficacy of immune-based cancer therapy for advanced malignancies...
  68. pmc Akt3-mediated resistance to apoptosis in B-RAF-targeted melanoma cells
    Yongping Shao
    Department of Cancer Biology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    Cancer Res 70:6670-81. 2010
    ..These findings delineate how mutant B-RAF protects melanoma cells from apoptosis and provide insight into possible resistance mechanisms to B-RAF inhibitors...
  69. ncbi Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer
    Martin J Schlumberger
    Institut Gustave Roussy, rue Camille Desmoulins, 94805 Villejuif Cedex, France
    J Clin Oncol 27:3794-801. 2009
    ....
  70. pmc Direct and differential suppression of myeloid-derived suppressor cell subsets by sunitinib is compartmentally constrained
    Jennifer S Ko
    Department of Immunology, Taussig Cancer Institute, and Glickman Urological Institute, Cleveland Clinic, Cleveland, Ohio, USA
    Cancer Res 70:3526-36. 2010
    ....
  71. ncbi Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors
    Lee S Rosen
    Premiere Oncology, Santa Monica, CA, USA
    J Clin Oncol 25:2369-76. 2007
    ..This phase I, dose-finding study evaluated the safety, pharmacokinetics, and pharmacodynamics of AMG 706 in patients with refractory advanced solid tumors...
  72. ncbi Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1
    Andrew D Napper
    Elixir Pharmaceuticals, One Kendall Square, Cambridge, Massachusetts 02139, USA
    J Med Chem 48:8045-54. 2005
    High-throughput screening against the human sirtuin SIRT1 led to the discovery of a series of indoles as potent inhibitors that are selective for SIRT1 over other deacetylases and NAD-processing enzymes...
  73. pmc The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint
    Silke Hauf
    Research Institute of Molecular Pathology, Dr Bohr Gasse 7, 1030 Vienna, Austria
    J Cell Biol 161:281-94. 2003
    ..Together, our data suggest that Aurora B is required to generate unattached kinetochores on monooriented chromosomes, which in turn could promote bipolar attachment as well as maintain checkpoint signaling...
  74. ncbi c-Met is a potentially new therapeutic target for treatment of human melanoma
    Neelu Puri
    Departments of Hematology Oncology and Pathology, University of Chicago Medical Center, Chicago, Illinois 60607, USA
    Clin Cancer Res 13:2246-53. 2007
    ..In this study, we investigated the role of c-Met in melanoma biology using a novel small-molecule tyrosine kinase inhibitor SU11274 and small interfering (si) RNA against the receptor...
  75. ncbi Inhibition of angiogenesis and invasion by 3,3'-diindolylmethane is mediated by the nuclear factor-kappaB downstream target genes MMP-9 and uPA that regulated bioavailability of vascular endothelial growth factor in prostate cancer
    Dejuan Kong
    Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA
    Cancer Res 67:3310-9. 2007
    ....
  76. ncbi Sequential FDG-PET/CT as a biomarker of response to Sunitinib in metastatic clear cell renal cancer
    Irfan Kayani
    Department of Nuclear Medicine, University College Hospital, London, UK
    Clin Cancer Res 17:6021-8. 2011
    ..Three sequential scans were conducted to determine whether the timing of the investigation was relevant...
  77. ncbi Why plants need more than one type of auxin
    Sibu Simon
    Institute of Experimental Botany, ASCR, Rozvojova 263, 16502 Praha 6, Czech Republic
    Plant Sci 180:454-60. 2011
    ..We present a scheme for homeostatic regulation of IAA levels that embraces other endogenous auxins in terms of the described mechanism of auxin action including its receptor and downstream signal transduction events...
  78. ncbi GSK-3-selective inhibitors derived from Tyrian purple indirubins
    Laurent Meijer
    CNRS, Cell Cycle Group, Station Biologique, BP 74, 29682 Roscoff Cedex, Bretagne, France
    Chem Biol 10:1255-66. 2003
    ..BIO but not 1-methyl-BIO closely mimicked Wnt signaling in Xenopus embryos. 6-bromoindirubins thus provide a new scaffold for the development of selective and potent pharmacological inhibitors of GSK-3...
  79. ncbi Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms
    Ralf Erber
    Department of Neurosurgery, Medical Faculty of the University of Heidelberg, Mannheim, Germany
    FASEB J 18:338-40. 2004
    ....
  80. ncbi Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice
    Julie Vignisse
    School for Mental Health and Neuroscience, Department of Neuroscience, Maastricht University, Universiteitssingel 50, NL 6229 ER Maastricht, The Netherlands
    Prog Neuropsychopharmacol Biol Psychiatry 35:510-22. 2011
    ..Acute treatment of water-deprived and non-water-deprived mice with dimebon also did not affect their water intake. Our data suggest that dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory tasks in mice...
  81. ncbi Myzus persicae (green peach aphid) feeding on Arabidopsis induces the formation of a deterrent indole glucosinolate
    Jae Hak Kim
    Boyce Thompson Institute for Plant Research, Tower Road, Ithaca, NY 14853, USA
    Plant J 49:1008-19. 2007
    ..Together, these results demonstrate that, in response to aphid feeding, Arabidopsis plants convert one indole glucosinolate to another that provides a greater defensive benefit...
  82. ncbi Molecular mechanisms of indirubin and its derivatives: novel anticancer molecules with their origin in traditional Chinese phytomedicine
    Gerhard Eisenbrand
    Division of Food Chemistry and Environmental Toxicology, Department of Chemistry, University of Kaiserslautern, P O Box 3049, 67663, Kaiserslautern, Germany
    J Cancer Res Clin Oncol 130:627-35. 2004
    ..This novel family of compounds holds strong promise for clinical anticancer activity and might be useful also in several important noncancer indications, including Alzheimer's disease or diabetes...
  83. pmc Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3'-diindolylmethane in healthy subjects
    Gregory A Reed
    Departments of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA
    Cancer Epidemiol Biomarkers Prev 17:2619-24. 2008
    ..We conclude that BR-DIM is well tolerated at single doses of up to 200 mg, and that increasing the dose to 300 mg did not result in an increase in C(max)...
  84. pmc Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells
    Hyun Ju Choi
    Department of Food Science and Nutrition, Hallym University, Chuncheon, Republic of Korea
    BMC Gastroenterol 9:39. 2009
    ..In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells...
  85. ncbi Identification of indole glucosinolate breakdown products with antifeedant effects on Myzus persicae (green peach aphid)
    Jae Hak Kim
    Boyce Thompson Institute for Plant Research, Ithaca, NY 14853, USA
    Plant J 54:1015-26. 2008
    ..persicae. Therefore, the post-ingestive breakdown of indole glucosinolates provides a defense against herbivores such as aphids that can avoid glucosinolate activation by plant myrosinases...
  86. pmc Down-regulation of uPA and uPAR by 3,3'-diindolylmethane contributes to the inhibition of cell growth and migration of breast cancer cells
    Aamir Ahmad
    Department of Pathology, Barbara Ann Karmanos Cancer Center, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    J Cell Biochem 108:916-25. 2009
    ....
  87. ncbi The pan-DAC inhibitor LBH589 is a multi-functional agent in breast cancer cells: cytotoxic drug and inducer of sodium-iodide symporter (NIS)
    N Fortunati
    Oncological Endocrinology, AOU San Giovanni Battista, University of Turin, Turin, Italy
    Breast Cancer Res Treat 124:667-75. 2010
    ..In conclusion, our data suggest that LBH589 might be a powerful tool in the management of breast cancer due to its multiple effects and support a potential application of LBH589 in the diagnosis and treatment of this disease...
  88. ncbi Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors
    Chandrajit P Raut
    Department of Surgery, Brigham and Women s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    J Clin Oncol 24:2325-31. 2006
    ..To assess the role of surgery in multimodality management of GISTs, we studied postoperative outcomes in patients treated with targeted kinase inhibitors for advanced GIST...
  89. ncbi SU11248 maintenance therapy prevents tumor regrowth after fractionated irradiation of murine tumor models
    Aaron J Schueneman
    Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    Cancer Res 63:4009-16. 2003
    ..Moreover, inhibition of angiogenesis well beyond radiation therapy may be a promising treatment paradigm for refractory human neoplasms...
  90. ncbi Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors
    Purva Bali
    Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida 33612, USA
    J Biol Chem 280:26729-34. 2005
    ..Depletion of HDAC6 sensitized human leukemia cells to HAA-HDIs and proteasome inhibitors...
  91. ncbi Development of the pan-DAC inhibitor panobinostat (LBH589): successes and challenges
    Peter Atadja
    Novartis Institutes for BioMedical Research, Cambridge, MA, USA
    Cancer Lett 280:233-41. 2009
    ....
  92. ncbi Gene expression profiling revealed survivin as a target of 3,3'-diindolylmethane-induced cell growth inhibition and apoptosis in breast cancer cells
    Km Wahidur Rahman
    Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA
    Cancer Res 66:4952-60. 2006
    ..These results suggest that targeting survivin by 3,3'-diindolylmethane could be a new and novel approach for the prevention and/or treatment of breast cancer...
  93. pmc Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032
    Jonas N Søndergaard
    Department of Medicine, Division of Hematology Oncology, University of California Los Angeles, Los Angeles, CA, USA
    J Transl Med 8:39. 2010
    ..In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity...
  94. ncbi The ABC transporter BcatrB from Botrytis cinerea exports camalexin and is a virulence factor on Arabidopsis thaliana
    Francesca L Stefanato
    Department of Biology, University of Fribourg, Chemin du Musée 8, CH 1700 Fribourg, Switzerland
    Plant J 58:499-510. 2009
    ..Here we demonstrate that an ABC transporter is a virulence factor that increases tolerance of the pathogen towards a phytoalexin, and the complete restoration of virulence on host plants lacking this phytoalexin...
  95. ncbi Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction
    Ke Ding
    Department of Internal Medicine, Comprehensive Cancer Center, Life Sciences Institute, University of Michigan, 1500 E Medical Center Drive, Ann Arbor, 48109, USA
    J Med Chem 49:3432-5. 2006
    ..MI-63 has excellent specificity over cancer cells with deleted p53 and shows a minimal toxicity to normal cells...
  96. ncbi AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts
    Anthony Polverino
    Department of Oncology Research, Amgen, Inc, Thousand Oaks, CA 91320 1799, USA
    Cancer Res 66:8715-21. 2006
    ..In summary, AMG 706 is an orally bioavailable, well-tolerated multikinase inhibitor that is presently under clinical investigation for the treatment of human malignancies...
  97. 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)...
  98. ncbi First-line treatment of advanced breast cancer with sunitinib in combination with docetaxel versus docetaxel alone: results of a prospective, randomized phase III study
    Jonas Bergh
    Karolinska Institutet and University Hospital, 171 76 Stockholm, Sweden
    J Clin Oncol 30:921-9. 2012
    ..To investigate whether sunitinib plus docetaxel improves clinical outcomes for patients with human epidermal growth factor receptor 2 (HER2)/neu-negative advanced breast cancer (ABC) versus docetaxel alone...
  99. pmc Physiological studies of tryptophan transport and tryptophanase operon induction in Escherichia coli
    C Yanofsky
    Department of Biological Sciences, Stanford University, California 94305 5020
    J Bacteriol 173:6009-17. 1991
    ..Our studies assign roles to the three permeases in tryptophan transport under different physiological conditions...
  100. ncbi Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial
    Nicholas J Robert
    Virginia Cancer Specialists, US Oncology, Fairfax, VA, USA
    Clin Breast Cancer 11:82-92. 2011
    ....
  101. ncbi Antioxidant activity of 5,10-dihydroindeno[1,2-b]indoles containing substituents on dihydroindeno part
    Oktay Talaz
    Department of Chemistry, Faculty of Sciences, Ataturk University, 25240 Erzurum, Turkey
    Bioorg Med Chem 17:6583-9. 2009
    An efficient synthesis of 5,10-dihydroindeno[1,2-b]indoles (3a-t) containing substituents such as methoxy, hydroxyl, and halogen (F, Cl, and Br) on indeno part was described...

Research Grants62

  1. Synthesis of Medicinally Important Heterocycles
    RICHARD LAROCK; Fiscal Year: 2007
    ..and extended to a wide variety of additional cyclizations including coumestans, furocoumarins, furoflavones, indoles, benzoselenophenes, benzolactams, dihydropyrimidines, 2-furanones, 2-pyrrolinones, benzopyrans, chromones and ..
  2. NOVEL PALLADIUM CATALYZED SYNTHESES OF INDOLE ALKALOIDS
    BJORN SODERBERG; Fiscal Year: 2001
    ..tryptamines, beta-carbolines, 1,2,3,4-tetrahydro-beta-carbolines, pyrrolo[4,3,2-de]quinolines, and pyrrolo[3,2d]indoles will be pursued...
  3. Role of natural indoles in experimental autoimmune encephalomyelitis
    Mitzi Nagarkatti; Fiscal Year: 2013
    ..Dietary indoles including indole-3-carbinol (I3C) found in cruciferous vegetables such as cauliflower, cabbage and Brussels ..
  4. Pilot-Scale Heterocyclic and Carbocyclic Libraries for High Throughout Screening
    RICHARD LAROCK; Fiscal Year: 2009
    ..annulation of alkynes, dienes, alkenes and arynes will be employed to prepare specially diverse libraries of indoles, benzofurans, benzopyrans, coumarins, isocoumarins, phthalides, pyrones, 2-quinolones, pyridines, isoquinolin-1-..
  5. Comparative Mechanisms of Cancer Chemoprevention
    Roderick H Dashwood; Fiscal Year: 2013
    ..Biomarkers Core, this competing continuation addresses the application (and possible risks) of dietary indoles and isothiocyanates for cancer intervention, through comparative mechanism, biomarker, and preclinical models (..
  6. Novel Targets of Indoles in Prostate Cancer
    Fazlul H Sarkar; Fiscal Year: 2013
    ..The results of our study will help to design mechanism-based clinical trials for assessing the role of B-DIM in the prevention and/or treatment of PCa. ..
  7. Metabolism of Carcinogens and Drugs by Human P450s
    F Peter Guengerich; Fiscal Year: 2013
    ..14a-demethylation), 19A1 (aromatase, oxidation of testosterone to 17p-estradiol), and 2A6 (oxidation of indoles), wrth a goal of defining the processivity of these systems...
  8. Au/Pt Catalysis in the Synthesis of Elaborate N-Heterocycles: Methodology Develop
    Liming Zhang; Fiscal Year: 2013
    ..g., pyridines, pyrroles, oxazoles, pyrroline and indoles)...
  9. Dietary Prevention of Obesity-Enhanced Liver Cancer
    Elizabeth H Jeffery; Fiscal Year: 2012
    ..to carcinoma formation, 2) evaluate the impact of whole, freeze-dried broccoli, broccoli sprouts (containing no indoles), broccoli sprouts plus indole-3-carbinol (I3C), I3C alone or no additions, on preneoplasia and on HCC...
  10. CATECHOLAMINES AND SEROTONIN IN BLOOD PRESSURE CONTROL
    Curt Freed; Fiscal Year: 1991
    ..We found that only in the C1 nucleus were the electrochemical peaks for catechols and indoles reciprocally related to blood pressure for both hypertension and hypotension...
  11. N-Heterocycles from Azides through Rhodium-Catalyzed Nitrenoid Transfer
    TOM GREGORY DRIVER; Fiscal Year: 2012
    ..demonstrate that vinyl- and aryl azides are valuable precursors for the transition metal-catalyzed synthesis of indoles, pyrroles, and carbazoles...
  12. SPECIES DIFFERENCE IN THE BIOTRANSFORMATION OF AFLATOXIN
    David Eaton; Fiscal Year: 2003
    ..In particular, specific chemical components of the diet, such as flavonoids, isocyanates, glucosinolates, indoles, dithiolthiones, and polyphenols have been identified as effective inducers and/or inhibitors of carcinogen ..
  13. Pilot Scale Libraries Inspired by Natural Products
    JEFFREY AUBE; Fiscal Year: 2012
    ..reactions of alkyl azides that afford complex ketones that are subsequently converted to carbamates, amines, indoles, or other heterocyclic products, (2) libraries based on a recently reported class of twisted lactams, (3) ..
  14. Efficient Assemblage of Complex Biologically-Active Targets Using Donor-Acceptor
    KEITH THOMAS MEAD; Fiscal Year: 2012
    ..be alkoxy-substituted benzenes, leading to the enantioselective synthesis of a known cytotoxic benzopyran, and indoles, potentially providing an efficient route to the tetracyclic core of dragmacidin E...
  15. STRUCTURAL BIOLOGY OF DIOXYGENASES
    Douglas Ohlendorf; Fiscal Year: 2003
    ..In plants and animals, dioxygenases are involved in the metabolism of indoles, aromatic amino acids, arachidonic acids and prostaglandins...
  16. Alkaloid Synthesis via Asymmetric C-CN Activation
    Christopher J Douglas; Fiscal Year: 2013
    Within the last few years, our laboratory discovered that important structural motifs in medicinal alkaloids, indoles and piperidines, could be synthesized with extraordinary ease using highly unusual reactivity...
  17. Discovery Based Studies of Medicinally Relevant Pharmacophore Libraries
    Matthew S Sigman; Fiscal Year: 2012
    ..architectures are broadly identified as 1) diarylmethines;2) 2-aminoimidazoles/cyclic guanidines and 3) dimeric indoles. Under the umbrella of these structural classes we have proposed the preparation of 14 chemical libraries to be ..
  18. CARCINOGENESIS--NITROSAMINE FORMATION AND INHIBITION
    RICHARD LOEPPKY; Fiscal Year: 1999
    ..imidates, thioimidates, geminal diamines and their S and O analogs, and certain benzylic-like amines linked to indoles, or other electron rich aromatic or heteroaromatic groups...
  19. Toxicological Control Mechanisms of Human CYP1A2
    LINDA QUATTROCHI; Fiscal Year: 2004
    ..g. heterocyclic amines, flavones, indoles) and genetic factors...
  20. Selective Peptide-Based Oxidation Catalysts for Bioactive Molecule Synthesis
    Scott J Miller; Fiscal Year: 2013
    ..We will also explore selective epoxidations of highly substituted, electron-rich arenes, such as indoles, that are relevant to natural product synthesis...
  21. PROTECTION FROM ENVIRONMENTAL TOXINS/MUTAGENS BY INDOLES
    HOWARD SHERTZER; Fiscal Year: 1990
    ..These studies will provide the basis for developing dietary and pharmacological strategies to reduce the risk associated with exposure to toxins that act via electrophilic or radical mechanisms...
  22. Genes, Hormones & Environment in an Ovarian Cancer Model
    Daniel Cramer; Fiscal Year: 2007
    ..from ovarian cancer is associated with a variety of antioxidants including lycopene, carotene, ginkgo, and indoles from Brassica vegetables as well as anti-inflammatory agents...
  23. REGIOSPECIFIC SYNTHESIS OF SUBSTITUTED INDOLES
    STANLEY RAUCHER; Fiscal Year: 1980
    ..The synthesis of these substituted indoles, their analogs, and their isotopically-labeled derivatives is often required for studies concerning their ..
  24. Strategies for the Synthesis of Bioactive Molecules -GM090007
    Neil K Garg; Fiscal Year: 2013
    ..Despite the development of an impressive array of strategies to synthesize functionalized indoles, methods to selectively substitute the indole benzenoid ring are limited...
  25. OXIDATION CHEMISTRY OF INDOLES
    Glenn Dryhurst; Fiscal Year: 2002
    ....
  26. SYNTHESIS OF NITROGEN CONTAINING NATURAL PRODUCTS
    Stephen Martin; Fiscal Year: 2010
    ..heterocycles and aromatic rings;and (4) new means for effecting diastereoselective, oxidative rearrangements of indoles to oxindoles...
  27. COUPLED ENZYME SYSTEMS TO PRODUCE TRYPTAMINE DERIVATIVES
    JAMES KILGORE; Fiscal Year: 2000
    Feasibility of a coupled-enzyme process to attach the aminoethyl group to the 3-positions of substituted indoles will be investigated...
  28. Condensations and Cyclizations to Bioactive Heterocycles
    Jon Rainier; Fiscal Year: 2003
    ..First, can we expand on our isonitrile-alkyne free-radical coupling chemistry to generate substituted indoles? Second, can we utilize thioamide-alkyne free-radical couplings to substituted indoles? Third, can we develop ..
  29. Synthesis of Pyrrole-Based Non-traditional Cannabinoids
    LEA PADGETT; Fiscal Year: 2004
    ..from the observation that certain aminoalkylindoles exhibit cannabinoid receptor affinity, several series of indoles and pyrroles have been designed and tested...
  30. NEW STRATEGIES FOR THE SYNTHESIS OF BIOACTIVE MOLECULES
    Raymond L Funk; Fiscal Year: 2010
    ..A novel method developed for the construction of indoles, a ubiquitous privileged structure found in numerous biologically active compounds, will be applied in the total ..
  31. New Methods and Strategies for the Synthesis of ETP Natural Products
    SARAH ELIZABETH REISMAN; Fiscal Year: 2013
    ..To this end, a new enantioselective formal [3+2] cycloaddition to prepare pyrrolidinoindolines directly from indoles will be developed. The specific aims are: 2...
  32. PERICYCLIC REACTIONS FOR ORGANIC SYNTHESIS
    Rick L Danheiser; Fiscal Year: 2010
    ..processes to provide efficient access to polycyclic benzo-fused heteroaromatic systems including indoles, dihydroquinolines, and benzazocines...
  33. ORGANOMETALLIC REAGENTS FOR CARBON/CARBON BOND FORMATION
    STEPHEN BUCHWALD; Fiscal Year: 2000
    ..zirconocene and titanocene complexes of arynes to prepare tricyclic metallacycles as a means for the synthesis of indoles and related heterocycles; 2) the development of simple techniques for the preparation of polysubstituted ..
  34. LASER-INDUCED NOVEL POTENTIAL ANTICANCER INDOLES
    GODWIN MBAGWU; Fiscal Year: 1990
    ..Absorption and fluorescence data will be analyzed using Scatchard equation. Photoproducts will be analyzed by HPLC and characterized by CHN elemental analysis and spectroscopically by IR, UV, 'HNMR, 13C NMR and MS...
  35. Total Synthesis of the Stephacidins
    Carlos Guerrero; Fiscal Year: 2007
    ..conditions can be found to reliably and efficiently prepare indolyl nitrones (imine N-oxides) from the parent indoles. Ideally, these and other strategies would be used prepare the stephacidins themselves as well as analogs not ..
  36. Synthesis of Cannabinoid Receptor Ligands
    John Huffman; Fiscal Year: 2005
    ..selective agonist properties and/or provide additional insight into the manner in which cannabimimetic indoles and pyrroles interact with each receptor...
  37. SYNTHESIS OF CANNABINOIDS, ANALOGUES AND METABOLITES
    John Huffman; Fiscal Year: 2009
    ..selective agonist properties and/or to provide additional insight into the manner in which cannabimimetic indoles and pyrroles interact with each receptor...
  38. Cruciferous Indoles in the Amelioration of the Metabolic Syndrome
    Andre Theriault; Fiscal Year: 2008
    ..The recent findings in our laboratory on the favorable effects of cruciferous indoles on lipid metabolism and the recent development of a hamster model of insulin resistance and metabolic ..
  39. Novel Single, Dual and Multitargeted Inhibitors of RTKs
    Aleem Gangjee; Fiscal Year: 2007
    ..abstract_text> ..
  40. Third Generation Antiopportunistic Agents
    Aleem Gangjee; Fiscal Year: 2003
    ..Screening against tuberculosis (NIAID) and tumor cells in culture (NCI) is also proposed. ..
  41. STRUCTURE BASED ANALOGS AS ANTIOPPORTUNISTIC AGENTS
    Aleem Gangjee; Fiscal Year: 2001
    ..The analogues synthesized will also be submitted for screening against tuberculosis (NIAID) parasitic diseases (WHO) and tumor cells in culture (NCI). ..
  42. Alpha Folate Receptor Mediated GARFTase Inhibitors as Selective Antitumor Agents
    Aleem Gangjee; Fiscal Year: 2010
    ....
  43. Single Agents with Designed Combination Chemotherapy Potential
    Aleem Gangjee; Fiscal Year: 2010
    ..abstract_text> ..
  44. 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. ..
  45. Synthesis of Macrolides, Steroids, Cyclopentanoids, etc.
    BARRY TROST; Fiscal Year: 2009
    ..These new synthetic methods apply to many structural types beyond those illustrated and constitutes a significant to gain access to complex molecular targets more easily. ..
  46. 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. ..
  47. NOVEL NONINDUCIBLE THYMIDYLATE SYNTHASE INHIBITORS
    Aleem Gangjee; Fiscal Year: 2004
    ....
  48. ASYMMETRIC SYNTHESIS OF VANCOMYCIN ANTIBIOTICS
    David Evans; Fiscal Year: 2001
    ..During the course of this project we intend to confirm (correct) the absolute stereochemical assignments of the principal members of this family by total synthesis. ..
  49. 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. ..
  50. Developmental Psychopharmacology of Antipsychotics
    JENNY WILEY; Fiscal Year: 2007
    ..This information will help to provide a more rational basis for making treatment decisions concerning children and adolescents who may benefit from treatment with an antipsychotic. [unreadable] [unreadable]..
  51. ASYMMETRIC SYNTHESIS OF IONOPHORE/MACROLIDE ANTIBIOTICS
    David Evans; Fiscal Year: 2005
    ..Our goal has been to set in place all of the reactions necessary for the rapid assemblage of any polyketide target structure. ..
  52. New Methodology for Indole Alkaloid Syntheses
    Ken S Feldman; Fiscal Year: 2010
    ..A new approach to C(3)/C(4)-cycloheptane-bridged indoles that features sequential Witkop and Dieckmann cyclizations is at the core of the synthesis strategy for these ..
  53. 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. ..
  54. Chemical and Biological Studies on Biaryl Phenolics
    Ken Feldman; Fiscal Year: 2005
    ..The search for selective 20S proteosome inhibitors among the Ntn-type proteases will be advanced by these investigations. ..
  55. Synthesis of Polyketides and Terpenes
    David A Evans; Fiscal Year: 2010
    ..As a consequence, organic synthesis is a critical discipline that continues to have an important impact on the fields of both medicine and biology. ..
  56. Alkynyliodonium Salts and Derived Diyls in Synthesis
    Ken Feldman; Fiscal Year: 2009
    ..abstract_text> ..
  57. DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS
    Arun K Ghosh; Fiscal Year: 2010
    ..This research integrates organic synthesis, protein-ligand x-ray crystallography, molecular modeling and in-depth virus and cell-biological studies to design the next generation of HIV-1 protease inhibitors. ..
  58. TRIPTYCENE ANALOGS--NOVEL BIFUNCTIONAL ANTICANCER DRUGS
    Jean Pierre Perchellet; Fiscal Year: 2004
    ..abstract_text> ..
  59. Regulation of the P13K/AKT pathway in Waldenstrom Macroglobulinemia
    Irene Ghobrial; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..