hydroxamic acids

Summary

Summary: A class of weak acids with the general formula R-CONHOH.

Top Publications

  1. ncbi Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex
    X Nan
    Institute of Cell and Molecular Biology, University of Edinburgh, UK
    Nature 393:386-9. 1998
  2. ncbi Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen
    C J Phiel
    Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA
    J Biol Chem 276:36734-41. 2001
  3. pmc Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells
    Xavier Contreras
    Department of Medicine, University of California, San Francisco, California 94143, USA
    J Biol Chem 284:6782-9. 2009
  4. ncbi Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
    S Imai
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 403:795-800. 2000
  5. ncbi HDAC inhibitors in cancer biology: emerging mechanisms and clinical applications
    Omar Khan
    Laboratory of Cancer Biology, Department of Oncology, Oxford, UK
    Immunol Cell Biol 90:85-94. 2012
  6. ncbi Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug
    Paul A Marks
    Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Nat Biotechnol 25:84-90. 2007
  7. pmc The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2
    Oliver H Kramer
    Georg Speyer Haus, Paul Ehrlich Strasse 42 44, D 60596 Frankfurt, Germany
    EMBO J 22:3411-20. 2003
  8. pmc Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease
    Emma Hockly
    Medical and Molecular Genetics, Guy s, King s and St Thomas School of Medicine, King s College London, Eighth Floor Guy s Tower, Guy s Hospital, London SE1 9RT, United Kingdom
    Proc Natl Acad Sci U S A 100:2041-6. 2003
  9. 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
  10. ncbi Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer
    Satoshi Kishigami
    Laboratory for Genomic Reprogramming, Center for Developmental Biology, RIKEN Kobe, 2 2 3 Minatojima minamimachi, Kobe 650 0047, Japan
    Biochem Biophys Res Commun 340:183-9. 2006

Detail Information

Publications306 found, 100 shown here

  1. ncbi Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex
    X Nan
    Institute of Cell and Molecular Biology, University of Edinburgh, UK
    Nature 393:386-9. 1998
    ..The data suggest that two global mechanisms of gene regulation, DNA methylation and histone deacetylation, can be linked by MeCP2...
  2. ncbi Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen
    C J Phiel
    Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA
    J Biol Chem 276:36734-41. 2001
    ..Based on these observations, we propose that inhibition of histone deacetylase provides a mechanism for valproic acid-induced birth defects and could also explain the efficacy of valproic acid in the treatment of bipolar disorder...
  3. pmc Suberoylanilide hydroxamic acid reactivates HIV from latently infected cells
    Xavier Contreras
    Department of Medicine, University of California, San Francisco, California 94143, USA
    J Biol Chem 284:6782-9. 2009
    ..Thus SAHA, which is a Food and Drug Administration-approved drug, might be considered to accelerate the decay of the latent reservoir in HAART-treated infected humans...
  4. ncbi Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
    S Imai
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 403:795-800. 2000
    ..These findings provide a molecular framework of NAD-dependent histone deacetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes...
  5. ncbi HDAC inhibitors in cancer biology: emerging mechanisms and clinical applications
    Omar Khan
    Laboratory of Cancer Biology, Department of Oncology, Oxford, UK
    Immunol Cell Biol 90:85-94. 2012
    ....
  6. ncbi Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug
    Paul A Marks
    Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Nat Biotechnol 25:84-90. 2007
    ..A new drug application was approved by the US Food and Drug Administration for vorinostat for treatment of cutaneous T-cell lymphoma. More potent analogs of SAHA have shown unacceptable toxicity...
  7. pmc The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2
    Oliver H Kramer
    Georg Speyer Haus, Paul Ehrlich Strasse 42 44, D 60596 Frankfurt, Germany
    EMBO J 22:3411-20. 2003
    ..Thus, poly-ubiquitination and proteasomal degradation provide an isoenzyme-selective mechanism for downregulation of HDAC2...
  8. pmc Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease
    Emma Hockly
    Medical and Molecular Genetics, Guy s, King s and St Thomas School of Medicine, King s College London, Eighth Floor Guy s Tower, Guy s Hospital, London SE1 9RT, United Kingdom
    Proc Natl Acad Sci U S A 100:2041-6. 2003
    ..SAHA dramatically improved the motor impairment in R6/2 mice, clearly validating the pursuit of this class of compounds as HD therapeutics...
  9. 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...
  10. ncbi Significant improvement of mouse cloning technique by treatment with trichostatin A after somatic nuclear transfer
    Satoshi Kishigami
    Laboratory for Genomic Reprogramming, Center for Developmental Biology, RIKEN Kobe, 2 2 3 Minatojima minamimachi, Kobe 650 0047, Japan
    Biochem Biophys Res Commun 340:183-9. 2006
    ..Thus, our data indicate that TSA-treatment after SCNT in mice can dramatically improve the practical application of current cloning techniques...
  11. pmc Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation
    Christopher G Vecsey
    Neuroscience Graduate Group, University of Pennsylvania, 19104, USA
    J Neurosci 27:6128-40. 2007
    ..Our results suggest that HDAC inhibitors enhance memory processes by the activation of key genes regulated by the CREB:CBP transcriptional complex...
  12. ncbi Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors
    M S Finnin
    Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nature 401:188-93. 1999
    ..These structures also suggest a mechanism for the deacetylation reaction and provide a framework for the further development of HDAC inhibitors as antitumour agents...
  13. ncbi Regulation of histone acetylation during memory formation in the hippocampus
    Jonathan M Levenson
    Baylor College of Medicine, Department of Neuroscience, Houston, Texas 77030, USA
    J Biol Chem 279:40545-59. 2004
    ..Mimicking memory-associated changes in heterochromatin enhances a cellular process thought to underlie long term memory formation, hippocampal long term potentiation, and memory formation itself...
  14. pmc Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation
    V M Richon
    DeWitt Wallace Research Laboratory, Cell Biology Program, Memorial Sloan Kettering Cancer Center and Graduate School of Medical Sciences of Cornell Medical School, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 97:10014-9. 2000
    ..Thus, the present findings indicate that the induction of p21(WAF1) by SAHA is regulated, at least in part, by the degree of acetylation of the gene-associated histones and that this induced increase in acetylation is gene selective...
  15. ncbi Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation
    Jim P Dompierre
    Institut Curie and Centre National de la Recherche Scientifique Unité Mixte de Recherche 146, Orsay, France
    J Neurosci 27:3571-83. 2007
    ..Our findings reveal that HDAC6 inhibition and acetylation at lysine 40 of alpha-tubulin may be therapeutic targets of interest in disorders such as HD in which intracellular transport is altered...
  16. pmc HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination
    Shanthi Adimoolam
    Pharmacyclics, Inc, Sunnyvale, CA 94085 4521, USA
    Proc Natl Acad Sci U S A 104:19482-7. 2007
    ..Together these results demonstrate that HDAC enzymes are critically important to enable functional HR by controlling the expression of HR-related genes and promoting the proper assembly of HR-directed subnuclear foci...
  17. pmc A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer
    P N Munster
    Division of Hematology and Oncology, University of California, San Francisco, 1600 Divisadero, Rm A719 Box 1711, San Francisco, CA 94143, USA
    Br J Cancer 104:1828-35. 2011
    ..Preclinically, HDAC inhibitors can reverse tamoxifen/aromatase inhibitor resistance in hormone receptor-positive breast cancer. This concept was examined in a phase II combination trial with correlative end points...
  18. pmc Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer
    William Kevin Kelly
    Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Joan and Sanford Weill Medical College of Cornell University, New York, NY 10021, USA
    J Clin Oncol 23:3923-31. 2005
    ..To determine the safety, dosing schedules, pharmacokinetic profile, and biologic effect of orally administered histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in patients with advanced cancer...
  19. pmc Identification and functional significance of genes regulated by structurally different histone deacetylase inhibitors
    Melissa J Peart
    The Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne 3002, Victoria, Australia
    Proc Natl Acad Sci U S A 102:3697-702. 2005
    ....
  20. ncbi Histone acetylation-independent effect of histone deacetylase inhibitors on Akt through the reshuffling of protein phosphatase 1 complexes
    Chang Shi Chen
    Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA
    J Biol Chem 280:38879-87. 2005
    ....
  21. pmc Vorinostat induces reactive oxygen species and DNA damage in acute myeloid leukemia cells
    Luca A Petruccelli
    Lady Davis Institute for Medical Research, Segal Cancer Center, Jewish General Hospital, McGill University, Montreal, Canada
    PLoS ONE 6:e20987. 2011
    ..This supports the continued study and development of vorinostat in AMLs that may be sensitive to DNA-damaging agents and as a combination therapy with ionizing radiation and/or other DNA damaging agents...
  22. pmc Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells
    Warren Fiskus
    Medical College of Georgia Cancer Center, Augusta, GA30912, USA
    Blood 114:2733-43. 2009
    ..These findings indicate that the combination of DZNep and panobinostat is effective and relatively selective epigenetic therapy against AML cells...
  23. ncbi Phase II trial of the histone deacetylase inhibitor vorinostat (Zolinza, suberoylanilide hydroxamic acid, SAHA) in patients with recurrent and/or metastatic head and neck cancer
    George R Blumenschein
    Department of Thoracic and Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Invest New Drugs 26:81-7. 2008
    ..Oral vorinostat 400 mg qd was generally well tolerated but did not demonstrate efficacy as defined by tumor response in this small group of heavily pre-treated patients...
  24. pmc Role of thioredoxin in the response of normal and transformed cells to histone deacetylase inhibitors
    J S Ungerstedt
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 102:673-8. 2005
    ..Thus, Trx, independent of the caspase apoptotic pathway, is an important determinant of resistance of cells to HDACi-induced cell death...
  25. pmc Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy
    Amy M Avila
    Neurogenetics Branch, National Institute of Neurological Disorders and Stroke NINDS, NIH, Bethesda, MA 20892, USA
    J Clin Invest 117:659-71. 2007
    ..These results indicate that the hydroxamic acid class of HDAC inhibitors activates SMN2 gene expression in vivo and has an ameliorating effect on the SMA disease phenotype when administered after disease onset...
  26. ncbi Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma
    Elise A Olsen
    Duke University, Durham, NC, USA
    J Clin Oncol 25:3109-15. 2007
    ....
  27. ncbi Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profiles in cutaneous T-cell lymphoma
    Leigh Ellis
    Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
    Clin Cancer Res 14:4500-10. 2008
    ..Herein, we report the safety and activity of the histone deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma (CTCL) and identify genes commonly regulated by panobinostat...
  28. ncbi CBP histone acetyltransferase activity is a critical component of memory consolidation
    Edward Korzus
    Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive 0986, La Jolla, CA 92093, USA
    Neuron 42:961-72. 2004
    ....
  29. ncbi Vorinostat/SAHA-induced apoptosis in malignant mesothelioma is FLIP/caspase 8-dependent and HR23B-independent
    Jane L Hurwitz
    Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen s University Belfast, Northern Ireland, UK
    Eur J Cancer 48:1096-107. 2012
    ..The histone deacetylase (HDAC) inhibitor Vorinostat (SAHA) is currently being evaluated in relapsed mesothelioma. We examined the roles of FLIP and caspase 8 in regulating SAHA-induced apoptosis in MPM...
  30. ncbi Deciphering the molecular events necessary for synergistic tumor cell apoptosis mediated by the histone deacetylase inhibitor vorinostat and the BH3 mimetic ABT-737
    Adrian P Wiegmans
    Gene Regulation Laboratory, Cancer Therapeutics Program, The Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia
    Cancer Res 71:3603-15. 2011
    ....
  31. pmc Histone deacetylase inhibitors induce VHL and ubiquitin-independent proteasomal degradation of hypoxia-inducible factor 1alpha
    Xianguo Kong
    Cardeza Foundation Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Mol Cell Biol 26:2019-28. 2006
    ..This degradation pathway involves the enhanced interaction of HIF-1alpha with HSP70 and is secondary to a disruption of the HSP70/HSP90 axis function that appears mediated by the activity of HDAC-6...
  32. ncbi Reversal of hypermethylation and reactivation of p16INK4a, RARbeta, and MGMT genes by genistein and other isoflavones from soy
    Ming Zhu Fang
    Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854 8020, USA
    Clin Cancer Res 11:7033-41. 2005
    ..To determine whether other polyphenolic compounds have similar activities, we studied the effects of soy isoflavones on DNA methylation...
  33. ncbi The novel histone deacetylase inhibitors metacept-1 and metacept-3 potently increase HIV-1 transcription in latently infected cells
    Miranda Shehu-Xhilaga
    Infectious Diseases Unit, Alfred Hospital, Melbourne, Victoria, Australia
    AIDS 23:2047-50. 2009
    ..Although these compounds had potent in-vitro activity, their cytotoxicity may limit their use in patients...
  34. pmc Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair
    J H Lee
    Cell Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:14639-44. 2010
    ..This DNA damage is associated with cancer cell death. These findings can explain, in part, the selectivity of vorinostat in causing cancer cell death at concentrations that cause little or no normal cell death...
  35. ncbi The siderophore system is essential for viability of Aspergillus nidulans: functional analysis of two genes encoding l-ornithine N 5-monooxygenase (sidA) and a non-ribosomal peptide synthetase (sidC)
    Martin Eisendle
    Department of Molecular Biology, University of Innsbruck, Fritz Pregl Str 3, A 6020 Innsbruck, Austria
    Mol Microbiol 49:359-75. 2003
    ..This indicates that the lack of this cellular iron storage compound causes oxidative stress. Moreover, ferricrocin biosynthesis was found to be crucial for efficient conidiation...
  36. pmc The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species
    A A Ruefli
    Cancer Immunology Division, The Peter MacCallum Cancer Institute, Trescowthick Research Laboratories, Saint Andrews Place, East Melbourne, Victoria 3002, Australia
    Proc Natl Acad Sci U S A 98:10833-8. 2001
    ..These data provide evidence of a mechanism of cell death mediated by transcriptional events that result in the cleavage of Bid, disruption of the mitochondrial membrane, and production of reactive oxygen species to induce cell death...
  37. ncbi Cell growth inhibition and gene expression induced by the histone deacetylase inhibitor, trichostatin A, on human hepatoma cells
    Tetsuhiro Chiba
    Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Inohana, Chuo Ward, Japan
    Oncology 66:481-91. 2004
    ..The effect of the HDAC inhibitor, trichostatin A (TSA), on hepatoma cells, however, has not been well studied. In this study, we examined cell viability and gene expression profile in hepatoma cell lines treated with TSA...
  38. pmc Expression of latent HIV induced by the potent HDAC inhibitor suberoylanilide hydroxamic acid
    Nancie M Archin
    University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    AIDS Res Hum Retroviruses 25:207-12. 2009
    ..These results suggest that potent, selective HDAC inhibitors may allow improved targeting of persistent proviral HIV infection, and define parameters for in vivo studies using SAHA...
  39. ncbi Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589
    David Z Qian
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Bunting Blaustein Cancer Research Building 1M52, 1650 Orleans Street, Baltimore, MS 21231, USA
    Clin Cancer Res 12:634-42. 2006
    ..Immunohistochemical analysis was done to evaluate new blood vessel formation in vivo...
  40. ncbi Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes
    Guillermo Garcia-Manero
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Blood 111:1060-6. 2008
    ..Increased histone acetylation was observed at all doses. Antioxidant gene expression may confer vorinostat resistance. Further evaluation of vorinostat in AML/MDS is warranted...
  41. ncbi The histone deacetylase inhibitor trichostatin A blocks progesterone receptor-mediated transactivation of the mouse mammary tumor virus promoter in vivo
    Melissa A Wilson
    Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 277:15171-81. 2002
    ....
  42. ncbi Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha
    David Z Qian
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA
    Cancer Res 66:8814-21. 2006
    ..Taken together, these results suggest that class II HDACs are associated with HIF-1 alpha stability and provide a rationale for targeting HIF-1 alpha with HDAC inhibitors against class II isozymes...
  43. ncbi Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor alpha
    Hideki Kawai
    Division of Experimental Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
    Int J Cancer 107:353-8. 2003
    ..Thus, HDAC1 may be a potential target for therapeutic intervention in the treatment of a subset of ER-negative breast cancers...
  44. pmc Role of autophagy in histone deacetylase inhibitor-induced apoptotic and nonapoptotic cell death
    Noor Gammoh
    Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 109:6561-5. 2012
    ....
  45. pmc TonB-dependent systems of uropathogenic Escherichia coli: aerobactin and heme transport and TonB are required for virulence in the mouse
    A G Torres
    Department of Microbiology and the Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas 78712, USA
    Infect Immun 69:6179-85. 2001
    ..These results indicate a role for TonB-dependent systems in the virulence of uropathogenic E. coli strains...
  46. pmc Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL)
    Madeleine Duvic
    Department of Dermatology, MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 434, Houston, TX 77030 4409, USA
    Blood 109:31-9. 2007
    ..Vorinostat demonstrated activity in heavily pretreated patients with CTCL. The 400 mg daily regimen had the most favorable safety profile and is being further evaluated...
  47. pmc SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6-Hsp90 chaperone axis
    D Li
    Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA
    Cell Death Differ 18:1904-13. 2011
    ..This identifies a novel action of SAHA with the prospect of SAHA becoming a centerpiece in mutp53-specific anticancer strategies...
  48. ncbi Role of the histone deacetylase complex in acute promyelocytic leukaemia
    R J Lin
    Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    Nature 391:811-4. 1998
    ..Our findings suggest that oncogenic RARs mediate leukaemogenesis through aberrant chromatin acetylation, and that pharmacological manipulation of nuclear receptor co-factors may be a useful approach in the treatment of human disease...
  49. ncbi Synergistic activation of functional estrogen receptor (ER)-alpha by DNA methyltransferase and histone deacetylase inhibition in human ER-alpha-negative breast cancer cells
    X Yang
    The Johns Hopkins Oncology Center, Johns Hopkins University, Baltimore, Maryland 21231, USA
    Cancer Res 61:7025-9. 2001
    ..These data suggest that the activities of both DNMT1 and HDAC are key regulators of methylation-mediated ER gene silencing...
  50. pmc Synergistic activation of human immunodeficiency virus type 1 promoter activity by NF-kappaB and inhibitors of deacetylases: potential perspectives for the development of therapeutic strategies
    Vincent Quivy
    Laboratoire de Virologie Moleculaire, Service de Chimie Biologique, Institut de Biologie et de Médecine Moléculaires, Universite Libre de Bruxelles, 6041 Gosselies, Belgium
    J Virol 76:11091-103. 2002
    ..Therefore, our results open new therapeutic strategies aimed at decreasing or eliminating the pool of latently HIV-infected reservoirs by forcing viral expression...
  51. ncbi Early phase II trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer
    Johan Vansteenkiste
    Respiratory Oncology Unit Pulmonology, University Hospital Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium
    Invest New Drugs 26:483-8. 2008
    ..Vorinostat in a daily oral schedule for 14 days/3 weeks was tolerable at 200 mg bid only, and no responses were observed in this study. Most patients, however, had limited drug exposure which did not allow a reliable efficacy analysis...
  52. pmc Histone deacetylase inhibitors downregulate checkpoint kinase 1 expression to induce cell death in non-small cell lung cancer cells
    William Brazelle
    Thoracic Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America
    PLoS ONE 5:e14335. 2010
    ....
  53. pmc Histone deacetylase inhibitors suppress rheumatoid arthritis fibroblast-like synoviocyte and macrophage IL-6 production by accelerating mRNA decay
    Aleksander M Grabiec
    Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Ann Rheum Dis 71:424-31. 2012
    ..Histone deacetylase inhibitors (HDACi) display potent therapeutic efficacy in animal models of arthritis and suppress inflammatory cytokine production in rheumatoid arthritis (RA) synovial macrophages and tissue...
  54. ncbi Array-based analysis of the effects of trichostatin A and CG-1521 on cell cycle and cell death in LNCaP prostate cancer cells
    Somdutta Roy
    Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA
    Mol Cancer Ther 7:1931-9. 2008
    ....
  55. ncbi Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action
    Hyeon Ju Kim
    Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Building 10, Bethesda, MD 20892 1363, USA
    J Pharmacol Exp Ther 321:892-901. 2007
    ..Given that there is no effective treatment for stroke, HDAC inhibitors, such as VPA, SB, and TSA, should be evaluated for their potential use for clinical trials in stroke patients...
  56. ncbi HDAC inhibitor vorinostat enhances the antitumor effect of gefitinib in squamous cell carcinoma of head and neck by modulating ErbB receptor expression and reverting EMT
    Francesca Bruzzese
    Experimental Pharmacology Unit, Department of Research, National Cancer Institute Fondazione G Pascale, Naples, Italy
    J Cell Physiol 226:2378-90. 2011
    ..Overall, this study suggests that the vorinostat/gefitinib combination represents a promising therapeutic strategy that warrants further clinical evaluation in SCCHN, including tumors intrinsically resistant to EGFR-inhibitors...
  57. ncbi Histone deacetylase inhibitors induce thyroid cancer-specific apoptosis through proteasome-dependent inhibition of TRAIL degradation
    E Borbone
    Istituto di Endocrinologia ed Oncologia Sperimentale, Naples, Italy
    Oncogene 29:105-16. 2010
    ..These results strongly encourage the preclinical application of the combination deacetylase-proteasome inhibitors for the treatment of ATC...
  58. pmc Molecular mechanisms of gene silencing mediated by DNA methylation
    Michela Curradi
    Dipartimento di Biologia Strutturale e Funzionale, Universita degli Studi dell Insubria, 21052 Busto Arsizio VA, Italy
    Mol Cell Biol 22:3157-73. 2002
    ....
  59. pmc Histone deacetylase inhibitors down-regulate bcl-2 expression and induce apoptosis in t(14;18) lymphomas
    Hong Duan
    Center for Molecular Biology in Medicine, Veterans Affairs, Palo Alto Health Care System, Palo Alto, CA, USA
    Mol Cell Biol 25:1608-19. 2005
    ..Mutation of Sp1 and C/EBPalpha binding sites reduced the TSA-induced repression of bcl-2 promoter activity. This study provides a mechanistic rationale for the use of HDAC inhibitors in the treatment of human t(14;18) lymphomas...
  60. pmc Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat
    Chandra R Tate
    Department of Medicine, Section of Hematology and Medical Oncology, Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112, USA
    Breast Cancer Res 14:R79. 2012
    ..Here, we investigate the ability of the histone deacetylase inhibitor panobinostat (LBH589) to selectively target triple-negative breast cancer (TNBC) cell proliferation and survival in vitro and tumorigenesis in vivo...
  61. pmc Differential response of cancer cells to HDAC inhibitors trichostatin A and depsipeptide
    J Chang
    Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390 8593, USA
    Br J Cancer 106:116-25. 2012
    ....
  62. pmc Inhibition of histone deacetylase overcomes rapamycin-mediated resistance in diffuse large B-cell lymphoma by inhibiting Akt signaling through mTORC2
    Mamta Gupta
    Division of Hematology and Department of Oncology, Mayo Clinic, Rochester, MN, USA
    Blood 114:2926-35. 2009
    ..These results provide a mechanistic rationale for a clinical trial of a combination of HDI and mTOR inhibitors for DLBCL...
  63. ncbi Melanoma cell lines are susceptible to histone deacetylase inhibitor TSA provoked cell cycle arrest and apoptosis
    Karita Peltonen
    Haartman Institute and Molecular Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Finland
    Pigment Cell Res 18:196-202. 2005
    ..The results indicate that while the action of TSA is independent of p53, the activation of the apoptosis pathway by the HDAC inhibitors may provide therapeutic approaches for melanoma treatment...
  64. pmc Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma
    Mark Kirschbaum
    City of Hope, Duarte, CA, USA
    J Clin Oncol 29:1198-203. 2011
    ..We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma...
  65. 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...
  66. ncbi Activity of deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma models: Defining molecular mechanisms of resistance
    Wenlin Shao
    Novartis Institutes for BioMedical Research, Oncology Drug Discovery, Cambridge, MA
    Int J Cancer 127:2199-208. 2010
    ..These data provide preclinical support that panobinostat, as a single agent or in combination with other anticancer agents, is a promising therapy for CTCL...
  67. 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...
  68. pmc Histone deacetylase inhibitors induce remission in transgenic models of therapy-resistant acute promyelocytic leukemia
    L Z He
    Molecular Biology Program and Department of Pathology, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Division, Graduate School of Medical Sciences, Cornell University, New York, New York 10021, USA
    J Clin Invest 108:1321-30. 2001
    ..In vivo, HDACIs induced accumulation of acetylated histones in target organs. Strikingly, this combination of agents induced leukemia remission and prolonged survival, without apparent toxic side effects...
  69. pmc Vorinostat enhances the radiosensitivity of a breast cancer brain metastatic cell line grown in vitro and as intracranial xenografts
    Andrew Baschnagel
    Radiation Oncology Branch, National Cancer Institute, 10 Center Drive, Bethesda, MD 20892, USA
    Mol Cancer Ther 8:1589-95. 2009
    ..There was a greater than additive improvement in survival in our intracranial model. Combining vorinostat with radiation may be a potential treatment option for patients with breast cancer who develop brain metastases...
  70. ncbi Effect of trichostatin A on chromatin remodeling, histone modifications, DNA replication, and transcriptional activity in cloned mouse embryos
    Hong Thuy Bui
    Department of Animal Biotechnology, College of Animal Bioscience and Biotechnology Animal Resources Research Center, Konkuk University, Seoul, Korea
    Biol Reprod 83:454-63. 2010
    ..This could enhance the reprogramming of somatic nuclei in terms of chromatin remodeling, histone modifications, DNA replication, and transcriptional activity...
  71. ncbi A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies
    Francis Giles
    Department of Leukemia, University of Texas M D Anderson Cancer Center, Houston, 77030, USA
    Clin Cancer Res 12:4628-35. 2006
    ..LBH589 is a novel histone deacetylase inhibitor that inhibits proliferation and induces apoptosis in tumor cell lines. In this phase I study, LBH589 was administered i.v. as a 30-minute infusion on days 1 to 7 of a 21-day cycle...
  72. ncbi Molecular sequelae of histone deacetylase inhibition in human malignant B cells
    Nicholas Mitsiades
    Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Blood 101:4055-62. 2003
    ....
  73. pmc Ku70 acetylation mediates neuroblastoma cell death induced by histone deacetylase inhibitors
    Chitra Subramanian
    Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA
    Proc Natl Acad Sci U S A 102:4842-7. 2005
    ..Whereas the Bax-binding ability of Ku70 allows it to block apoptosis in response to certain agents, it is also a molecular target for the action of HDACIs, and in this context, a mediator of NB cell death...
  74. pmc Inhibition of histone deacetylases promotes ubiquitin-dependent proteasomal degradation of DNA methyltransferase 1 in human breast cancer cells
    Qun Zhou
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, CRB Room 144, Baltimore, MD 21231, USA
    Mol Cancer Res 6:873-83. 2008
    ..Our studies suggest a new role for HDAC1 and identify a novel mechanism of action for the HDAC inhibitors as down-regulators of DNMT1...
  75. pmc Suppression of class I and II histone deacetylases blunts pressure-overload cardiac hypertrophy
    Yongli Kong
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 8573, USA
    Circulation 113:2579-88. 2006
    ..Thus, HDAC inhibitors hold promise as potential therapeutic agents in hypertrophic heart disease...
  76. pmc Histone hyperacetylation in mitosis prevents sister chromatid separation and produces chromosome segregation defects
    Daniela Cimini
    Institute of Molecular Biology and Pathology, National Research Council, c o Department of Genetics and Molecular Biology, University La Sapienza, 00185 Rome, Italy
    Mol Biol Cell 14:3821-33. 2003
    ....
  77. pmc The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding L-ornithine N5-oxygenase, is required for virulence
    Anna H T Hissen
    Department of Biological Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada
    Infect Immun 73:5493-503. 2005
    ..Unlike the wild-type and rescued strains, the DeltasidA strain was avirulent in a mouse model of invasive aspergillosis, indicating that sidA is necessary for A. fumigatus virulence...
  78. 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
    ....
  79. pmc A phase II trial of vorinostat (suberoylanilide hydroxamic acid) in metastatic breast cancer: a California Cancer Consortium study
    Thehang H Luu
    Division of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Duarte, California 91010, USA
    Clin Cancer Res 14:7138-42. 2008
    ..The secondary goals included assessment of time to progression, evaluation of toxicities, and overall survival...
  80. ncbi Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling
    Christophe F Deroanne
    Research Center in Experimental Cancerology, University of Liege, Sart Tilman, B 4000 Liege, Belgium
    Oncogene 21:427-36. 2002
    ..These observations provide a conspicuous demonstration that HDAC inhibitors are potent anti-angiogenic factors altering VEGF signaling...
  81. pmc Characterization of a human RPD3 ortholog, HDAC3
    S Emiliani
    Picower Institute for Medical Research, Manhasset, NY 11030, USA
    Proc Natl Acad Sci U S A 95:2795-800. 1998
    ..These observations identify another member of a growing family of human HDAC genes...
  82. pmc A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases
    V M Richon
    Cell Biology Program, Memorial Sloan Kettering Cancer Center 1275 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 95:3003-7. 1998
    ..These studies show that the second-generation HPCs, unlike HMBA, are potent inhibitors of HDAC activity. In this sense, HMBA and the second-generation HPCs appear to induce differentiation by different pathways...
  83. pmc Role of acetylation and extracellular location of heat shock protein 90alpha in tumor cell invasion
    Yonghua Yang
    Medical College of Georgia Cancer Center, Augusta, Georgia, USA
    Cancer Res 68:4833-42. 2008
    ..Thus, reversible hyperacetylation modulates the intracellular and extracellular chaperone function of hsp90, and targeting extracellular hyperacetylated hsp90alpha may undermine tumor invasion and metastasis...
  84. ncbi Duration of nuclear NF-kappaB action regulated by reversible acetylation
    - Chen Lf
    Gladstone Institute of Virology and Immunology, Department of Medicine, University of California, San Francisco, CA 94141, USA
    Science 293:1653-7. 2001
    ....
  85. pmc Phase II trial of vorinostat in recurrent glioblastoma multiforme: a north central cancer treatment group study
    Evanthia Galanis
    Mayo Clinic, Gonda 10 141, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
    J Clin Oncol 27:2052-8. 2009
    ..Vorinostat, a histone deacetylase inhibitor, represents a rational therapeutic target in glioblastoma multiforme (GBM)...
  86. pmc SreA-mediated iron regulation in Aspergillus fumigatus
    Markus Schrettl
    Divisions of Molecular Biology Biocenter, Medical University Innsbruck, Fritz Pregl Str 3, A 6020 Innsbruck, Austria
    Mol Microbiol 70:27-43. 2008
    ..As all detrimental effects of sreA disruption are restricted to iron-replete conditions these data underscore that A. fumigatus faces iron-depleted conditions during infection...
  87. ncbi Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid specifically alters gene expression and reduces ischemic injury in the mouse brain
    Giuseppe Faraco
    Department of Preclinical and Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
    Mol Pharmacol 70:1876-84. 2006
    ..Data demonstrate that pharmacological inhibition of HDACs promotes expression of neuroprotective proteins within the ischemic brain and underscores the therapeutic potential of molecules inhibiting HDACs for stroke therapy...
  88. pmc Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling
    Wangsen Cao
    Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    J Exp Med 205:1491-503. 2008
    ..Our data suggest that acetylation of MKP-1 inhibits innate immune signaling. This pathway may be an important therapeutic target in the treatment of inflammatory diseases...
  89. ncbi Histone deacetylase inhibitor SAHA induces ERalpha degradation in breast cancer MCF-7 cells by CHIP-mediated ubiquitin pathway and inhibits survival signaling
    Xin Yi
    Department of Pathology, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, China
    Biochem Pharmacol 75:1697-705. 2008
    ..Taken together, our results revealed a mechanism for SAHA-induced ERalpha degradation and indicated that SAHA is a suitable pharmacological agent for depletion of ERalpha and a potential choice for breast cancer expressing high ERalpha...
  90. ncbi Hydroxamic acid analogue histone deacetylase inhibitors attenuate estrogen receptor-alpha levels and transcriptional activity: a result of hyperacetylation and inhibition of chaperone function of heat shock protein 90
    Warren Fiskus
    Medical College of Georgia Cancer Center, Augusta, Georgia 30912, USA
    Clin Cancer Res 13:4882-90. 2007
    ..Here, we determined the effect of HA-HDIs on the levels and activity of ERalpha, as well as on the survival of ERalpha-expressing, estrogen-responsive human breast cancer MCF-7 and BT-474 cells...
  91. ncbi Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced arthritis mouse model
    Y Nasu
    Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
    Osteoarthritis Cartilage 16:723-32. 2008
    ..To investigate the effect of the histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), on joint inflammation and cartilage degeneration in a collagen antibody-induced arthritis (CAIA) mouse model...
  92. ncbi Combination strategy targeting the hypoxia inducible factor-1 alpha with mammalian target of rapamycin and histone deacetylase inhibitors
    Henk M W Verheul
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, Cancer Research Building I, 1M52, Baltimore, MD 21231, USA
    Clin Cancer Res 14:3589-97. 2008
    ..Thus, we hypothesized that combination treatment of rapamycin and the HDAC inhibitor LBH589 has greater antiangiogenic and antitumor activity compared with single agents...
  93. ncbi A phase II study of vorinostat in the treatment of persistent or recurrent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study
    Susan C Modesitt
    University of Virginia Health System, Charlottesville, VA 22908, USA
    Gynecol Oncol 109:182-6. 2008
    ....
  94. ncbi EGFR-TKI resistance due to BIM polymorphism can be circumvented in combination with HDAC inhibition
    Takayuki Nakagawa
    Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, Japan
    Cancer Res 73:2428-34. 2013
    ..Together, our results show how HDAC inhibition can epigenetically restore BIM function and death sensitivity of EGFR-TKI in cases of EGFR-mutant NSCLC where resistance to EGFR-TKI is associated with a common BIM polymorphism...
  95. ncbi A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p
    J Taunton
    Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
    Science 272:408-11. 1996
    ..As the predicted protein is very similar to the yeast transcriptional regulator Rpd3p, these results support a role for histone deacetylase as a key regulator of eukaryotic transcription...
  96. ncbi Histone deacetylase inhibitor Trichostatin A induces global and gene-specific DNA demethylation in human cancer cell lines
    Jing Ni Ou
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    Biochem Pharmacol 73:1297-307. 2007
    ..Taken together, our data provide evidence for a reversible crosstalk between histone acetylation and DNA demethylation, which has significant implications on the use of HDAC inhibitors as therapeutic agents...
  97. ncbi Differential effects of histone deacetylase inhibitors on phorbol ester- and TGF-beta1 induced murine tissue inhibitor of metalloproteinases-1 gene expression
    David A Young
    School of Biological Sciences, University of East Anglia, Norwich, UK
    FEBS J 272:1912-26. 2005
    ....
  98. ncbi Histone deacetylase inhibitors profoundly decrease proliferation of human lymphoid cancer cell lines
    Sakura Sakajiri
    Division of Hematology Oncology, Cedars Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA
    Exp Hematol 33:53-61. 2005
    ..In nude mice, SAHA significantly inhibited growth of a mantle cell lymphoma without major toxic side effects. In summary, HDACIs are promising therapeutic agents for human lymphoid cancers...
  99. ncbi Small molecular anti-cytokine agents
    Gerd Wagner
    School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, NR4 7TJ, England
    Med Res Rev 26:1-62. 2006
    ..g., oral availability, solubility, cell penetration, etc.)...
  100. ncbi Histone deacetylase (HDAC) inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer
    Ling Geng
    Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Cancer Res 66:11298-304. 2006
    ..This study identifies HDAC4 as a biomarker of LBH589 activity and recognizes the ability of LBH589 to sensitize human NSCLC to radiation-induced DNA DSBs...
  101. ncbi Regulation of apoptosis-associated genes by histone deacetylase inhibitors: implications in cancer therapy
    Ali R Jazirehi
    Department of Surgery, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California, USA
    Anticancer Drugs 21:805-13. 2010
    ..Herein I review epigenetic modifications, discuss the various mechanisms of HDACi-induced effects, in particular modulation of expression of apoptosis-associated gene products, and highlight SAHA and its antitumor functions...

Research Grants63

  1. Histone Deacetylase Inhibitors in CML
    Kapil Bhalla; Fiscal Year: 2009
    ..abstract_text> ..
  2. Epigenetic downregulation of the antibody response and inhibition of autoimmunity
    Paolo Casali; Fiscal Year: 2013
    ....
  3. Heat shock protein 90 antagonist-based therapy of mantle cell lymphoma
    Kapil Bhalla; Fiscal Year: 2012
    ..This strategy involves combinations of treatments with heat shock protein 90 and proteosome inhibitors designed to target protein folding and degradation in MCL cells. ..
  4. Small-molecule inhibitors of hADAM12
    Jens Berthelsen; Fiscal Year: 2012
    ..Cross-validated compounds derived after primary and secondary assays will be further developed to enhance potency and selectivity for ADAM12. ! ..
  5. Inhibition of Autophagy: A Novel Therapeutic Strategy for Advanced Solid Tumors
    Francis J Giles; Fiscal Year: 2010
    ....
  6. Effects of Acitretin on the activation of latent HIV
    Peilin Li; Fiscal Year: 2013
    ....
  7. Histone Deacetylase Inhibitor Based Therapy of AML
    Kapil Bhalla; Fiscal Year: 2011
    ..The proposed pre-clinical studies could potentially define HAA-HDI based novel combinations and generate the rationale to test their in vivo efficacy against human AML cells. ..
  8. Global characterization of lysine acetylation in cancer by a proteomics approach
    Yingming Zhao; Fiscal Year: 2012
    ..abstract_text> ..
  9. Quantitative MRSI to predict early response to SAHA therapy in new GBM management
    Hui Kuo Shu; Fiscal Year: 2013
    ..Importantly, in addition to monitoring tumor response to SAHA therapy, our MRSI-based tool will allow assessment of the biochemical content of normal brain, and may thus indirectly monitor the subject's quality-of-life. ..
  10. Novel Small Molecule Inhibitors of Botulinum Neurotoxin A
    Terry L Bowlin; Fiscal Year: 2010
    ..By the end of this proposed research and pre-clinical development plan, our overall project milestone is to file an IND for the clinical human safety evaluation of an orally active small molecule BoNT/A inhibitor. ..
  11. Specific killing of latently HIV-1-infected cells after provirus reactivation
    Qigui Yu; Fiscal Year: 2013
    ..This approach may simultaneously target various latently infected cells and residual viremia, potentially leading to a broader impact and improved efficacy against the various persistent HIV-1 reservoirs. ..
  12. A Phase II/II Investigation of the Effect of Vorinostat (VOR) in HIV Infection
    David M Margolis; Fiscal Year: 2013
    ..Histone deacetylase (HDAC) inhibitors disrupt latent proviral infection ex vivo. We will directly assess the effect of HDAC inhibitors on HIV latency in vivo. ..
  13. Molecular Mechanisms of Class II HDAC inhibitors in Alzheimer's disease
    HYANG SOOK HOE; Fiscal Year: 2013
    ..Results from our study will provide the molecular mechanisms of action of Class II HDACIs on Ab production, Ab plaque formation, and cognitive function for future development of AD therapeutics. ..
  14. Novel agents against West Nile Virus infections
    Krzysztof Pankiewicz; Fiscal Year: 2003
    ..These two groups have similar pKa's but different shape and may show improved activity against WNV infection. ..
  15. NEW BCAS FOR RADIOIMMUNOTHERAPY WITH RADIOMETALS
    Donald Buchsbaum; Fiscal Year: 2001
    ..The experiments described in this application will provide answers to these questions. These studies would establish the rationale for human clinical RIT trials in patients with Jp. cancer using HuCC49ACH2. ..
  16. METABOLIC ACTIVATION OF ARYLAMINES IN LEUKOCYTES
    Michael Corbett; Fiscal Year: 1991
    ..Research will emphasize the ability of the various types of leukocytes to cause arylamines and aromatic hydroxamic acids to bind covalently with cellular macromolecules, a process which can lead to the disruption of normal cell ..
  17. Small Molecule Inhibitors of Anthrax Lethal Factor
    NORTON PEET; Fiscal Year: 2006
    ..abstract_text> ..
  18. SULFOTRANSFERASE INACTIVATION BY CARCINOGENS
    BONNIE MANGOLD; Fiscal Year: 1990
    ..in the bioactivation of several types of chemical carcinogens including safrole, aromatic hydroxylamines and hydroxamic acids, and hydroxyxanthines...
  19. AZACYCLIC SYNTHESIS USING N-SULFONYLOXY AMINES
    Robert Hoffman; Fiscal Year: 1993
    ..Fresh synthetic strategies to physiologically active azacyclic targets are developed with particular emphasis on systems that are problematic by traditional synthetic strategies...
  20. METABOLIC ACTIVATION OF UNSUBSTITUTED HYDROXAMIC ACID
    MEI SIE LEE; Fiscal Year: 1990
    Certain hydroxamic acids with the structure of ArCONHOH or RCONHOH are mutagenic for bacteria and mammalian cells, and teratogenic in experimental animals, and must, therefore, be regarded as potential environmental hazards...
  21. Targeting Non-mammalian Isoprenoid Biosynthesis
    CAREN L MEYERS; Fiscal Year: 2013
    ..Anti-infective agents developed to target these enzymes have the potential to broadly impact the treatment of deadly infectious diseases. ..
  22. Retinoids, RAMBAs, and Histone Deacetylase Inhibitors
    Vincent Njar; Fiscal Year: 2006
    ..The following specific aims that are proposed should enable us obtain substantial data that may support our hypothesis. ..
  23. The in vivo effect of HDAC Inhibitors on HIV gene expression in resting CD4+ T Ce
    David Margolis; Fiscal Year: 2009
    ..a limited exposure to VPA or VOR and measure acetylated histones, and histone acetylation at the human p21 gene in the peripheral blood cells of ART-treated, aviremic HIV-infected patients following a limited exposure to VPA or VOR ..
  24. Potentiation of Topo Inhibitors by the HDACi, SAHA
    Pamela Munster; Fiscal Year: 2007
    ..These findings may be useful in the rational design of future clinical trials involving HDACi. [unreadable] [unreadable]..
  25. HYDROXAMIC ACID PRODUCTION IN MICROBIAL ECOSYSTEMS
    Michael Corbett; Fiscal Year: 1980
    ..by this investigator has established that aromatic nitroso compounds are partially converted into aromatic hydroxamic acids by means of the action of certain thiamine dependent enzymes...
  26. Histone Deacetylase Inhibitors for Cancer Treatment
    Gerald Soff; Fiscal Year: 2005
    ..3) These compounds will be assayed for histone deacetylase activity and for antitumor activity in a variety of cancer cells. ..
  27. MECHANISTIC STUDIES OF ARYLAMIDE CARCINOGENS
    GRAHAM UNDERWOOD; Fiscal Year: 1990
    A systematic study will be made of the chemistry of O- substituted aryl hydroxamic acids. These are precursors to nitrenium ions which are generally regarded as the reactive intermediates involved in adduct formation between these ..
  28. NEW TECHNOLOGY IN ENZYMATIC SYNTHESIS
    Dale Drueckhammer; Fiscal Year: 2001
    ..This work is expected to contribute to the understanding of control mechanisms of cell growth and differentiation related to cancer due to the vital role of protein fatty acylation in signal transduction mechanisms. ..
  29. METALLOPROTEINASES AS MEDIATORS OF CNS INJURY IN AIDS
    Katherine Conant; Fiscal Year: 1999
    ..Also, compounds including the hydroxamic acid maramastat as well as select anti- oxidants and anti-inflammatory drugs, will be tested for their ability to inhibit the production, release and/or activity of specific MMPs. ..
  30. THERAPEUTIC MODULATION OF BREAST CANCER ONCOGENES
    Christopher Benz; Fiscal Year: 2007
    ..tumor-targeted uptake of selected candidates by encapsulation into anti-ErbB2 immunoliposomes (ILs), and these ErbB2 receptor- and promoter-targeted ILs agents will be evaluated in vivo for further clinical development ..
  31. Analysis of Circulating Tumor Cells in a Phase I/II Study for Breast Cancer
    Ramona Swaby; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  32. Translational Development of Novel MMP Inhibitors
    Seth M Cohen; Fiscal Year: 2010
    ..3. To evaluate novel MPIs using isolated working rat heart preparations. 4. To examine the effects of MPIs on in vivo ischemia reperfusion injury. ..
  33. CUTANEOUS ONCOLOGY
    Madeleine Duvic; Fiscal Year: 2004
    ..Young physicians and students who receive advanced training in the proper detection, prevention, and treatment of skin cancers will be a resource and may improve outcomes for patients of the future. ..
  34. IDENTIFICATION OF AGGRECANASE INHIBITORS: GENETIC SCREEN
    SUNEEL APTE; Fiscal Year: 2001
    ..Substrates can be modeled to design specific analog inhibitors as has been done in designing hydroxamic acid based MMP inhibitors. ..
  35. Chemistry and Pharmacology of a New Nicotine Ligands
    Alan Kozikowski; Fiscal Year: 2007
    ..Functional activity will be evaluated using established 86RbC1 efflux assays and/or whole cell patch clamp measurements. ..
  36. Cell Cycle Controlling Genes in Adult Acute Lymphoma
    Guillermo Garcia Manero; Fiscal Year: 2005
    ..abstract_text> ..
  37. BOEC in Biology
    Robert Hebbel; Fiscal Year: 2005
    ..Aside from eventual therapeutics, these studies will define aspects of this unique cell type. ..
  38. DESIGN OF LIGANDS SELECTIVE FOR THE DAG SUPERFAMILY
    Alan Kozikowski; Fiscal Year: 2002
    ..To assess the effect of alterations in the ligand's hydrophobic side chain on its tumor promoting activity, studies of skin hyperplasia will be conducted. ..
  39. TLS and TLS Fusion Proteins in Leukemia
    Liu Yang; Fiscal Year: 2005
    ..It is envisioned that successful completion of this project will unveil potential therapeutic targets in the treatment of human leukemias characterized by the t(16;21) translocation. ..
  40. CHEMICAL AND PHARMACOLOGICAL STUDIES OF COCAINE ANALOGS
    Alan Kozikowski; Fiscal Year: 2004
    ....
  41. Development of Oral Suberoylanilide Hydroxamic Acid
    William Kelly; Fiscal Year: 2003
    ..e.p21WAF1) in tumors. Subsequently, these findings will be correlated with the clinical outcomes. ..
  42. ERYTHROCYTE MEMBRANE ABNORMALITIES IN SICKLE DISEASE
    Robert Hebbel; Fiscal Year: 2002
    ..These studies will rigorously test our hypotheses regarding the participation of TSP and CD36 in mediating sickle RBC adhesion to endothelium. ..
  43. DEVELOPMENTAL HEMATO-ENDOTHELIAL BIOLOGY OF P1H12
    Robert Hebbel; Fiscal Year: 2002
    ..These studies represent a first step towards defining the role of P1H12 in embryology, with an emphasis on hematopoiesis and vasculogenesis (as rationalized by exciting preliminary data). ..
  44. DRUGS AND DELIVERY SYSTEMS FOR OPPORTUNISTIC INFECTIONS
    Marvin Miller; Fiscal Year: 2002
    ....
  45. Phase1/11 study of 5-aza-2'-deoxycytidine and valproic *
    Guillermo Garcia Manero; Fiscal Year: 2005
    ..Decitabine will be generously provided by SuperGen (r). Valproic acid is an FDA approved anti-convulsant. ..
  46. Epigenetic Control of Heterochromatin Formation
    Rabindranath De La Fuente; Fiscal Year: 2010
    ..abstract_text> ..
  47. CHONDROGENESIS AND HISTONE MODIFICATION ENZYMES
    Liu Yang; Fiscal Year: 2007
    ....
  48. PKC Modulators for the Treatment of Alzheimer's disease
    Alan Kozikowski; Fiscal Year: 2008
    ..For the best compounds from Aim 2, perform studies in triple transgenic mice to ascertain effects on Abeta and sAPPalpha levels and plaque formation in vivo. ..
  49. The Role of BCL-2 in Corneal Epithelial Cell Shedding
    DANIELLE ROBERTSON; Fiscal Year: 2008
    ..4) That events leading to increased apoptosis such as UV light signal surface cell apoptosis through the phosphorylation of BCL-2. ..
  50. Phase I study of 5-aza-2?-deoxycitidine in acute lymphocytic leukemia
    Guillermo Garcia Manero; Fiscal Year: 2008
    ..In this proposal, we plan to develop a new form of low-dose chemotherapy, decitabine, for these patients. Early results indicate that this is active and safe. [unreadable] [unreadable] [unreadable]..
  51. Mechanisms of IL-18 Mediated Regulation of GVHD and GVL
    Pavan Reddy; Fiscal Year: 2006
    ..The applicant's sponsor guarantees that 80% of Dr. Reddy's effort will be devoted to his research during this award. ..
  52. Derivatization/Functionalization of Natural Product(RMI)
    Marvin Miller; Fiscal Year: 2007
    ..3. Broadly test the scaffold and derived libraries of novel compounds using the extensive set of assays in place at the Hans-Knoll Institute for Natural Products Research (HKI). ..
  53. BIOLOGICAL STUDIES OF PIPERIDINE ANALOGS OF COCAINE
    Alan Kozikowski; Fiscal Year: 2001
    ..4. For compounds meeting set criteria, to further evaluate their behavioral pharmacological profile in animals using intravenous drug self-administration and drug discrimination procedures. ..
  54. The Role of Selective HDAC Enzymes in Drug Sensitivity
    Pamela N Munster; Fiscal Year: 2010
    ..In pre- and post-treatment tumor samples, we will determine which HDACs are involved in the cellular effects induced by the HDACi and which HDACs may predict response. ..
  55. Bioactive Compounds from Acylnitroso Cycloadducts
    Marvin Miller; Fiscal Year: 2006
    ..from Diels-Alder reactions of dienes with transient acyl nitroso moieties, generated by oxidation of hydroxamic acids, can serve as versatile building blocks for syntheses of a number of important and often novel bioactive ..
  56. ENDOTHELIAL CELL OUTGROWTH FROM BLOOD
    Robert Hebbel; Fiscal Year: 2001
    ..abstract_text> ..
  57. Chemistry and Biology of 5-HT2C Receptor Ligands for Drug Abuse
    ALAN PAUL KOZIKOWSKI; Fiscal Year: 2010
    ....