G Chiosis

Summary

Affiliation: Memorial Sloan-Kettering Cancer Center
Country: USA

Publications

  1. ncbi request reprint Emerging Hsp90 inhibitors: from discovery to clinic
    G Chiosis
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Anticancer Agents Med Chem 6:1-8. 2006
  2. pmc Assay strategies for the discovery and validation of therapeutics targeting Brugia pahangi Hsp90
    Tony Taldone
    Department of Molecular Pharmacology and Chemistry, Sloan Kettering Institute, New York, New York, United States of America
    PLoS Negl Trop Dis 4:e714. 2010
  3. pmc A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas
    Leandro C Cerchietti
    Division of Hematology and Oncology, Weill Cornell Medical College of Cornell University, New York, New York, USA
    Nat Med 15:1369-76. 2009
  4. ncbi request reprint Regulatory chaperone complexes in neurodegenerative diseases: a perspective on therapeutic intervention
    Aaron Carman
    Molecular Pharmacology and Chemistry, Sloan Kettering Institute, Associate Attending, Breast Cancer Service, Department of Medicine, Memorial Hospital, Memorial Sloan Kettering Cancer Center, ZRB2103, Associate Professor, Weill Graduate School of Medical Sciences, New York, USA
    Curr Alzheimer Res 11:59-68. 2014
  5. pmc Heat shock protein 90: translation from cancer to Alzheimer's disease treatment?
    Wenjie Luo
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University and Fisher Foundation for Alzheimer s Disease, New York, NY 10021, USA
    BMC Neurosci 9:S7. 2008
  6. ncbi request reprint Discovery and development of purine-scaffold Hsp90 inhibitors
    Gabriela Chiosis
    Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Curr Top Med Chem 6:1183-91. 2006
  7. ncbi request reprint Hsp90: the vulnerable chaperone
    Gabriela Chiosis
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Drug Discov Today 9:881-8. 2004
  8. ncbi request reprint Small molecule microarrays: from proteins to mammalian cells - are we there yet?
    Gabriela Chiosis
    Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Trends Biotechnol 23:271-4. 2005
  9. ncbi request reprint Targeting chaperones in transformed systems--a focus on Hsp90 and cancer
    Gabriela Chiosis
    Programme in Molecular Pharmacology and Chemistry, Department of Medicine, Memorial Sloan Kettering Cancer Center, Box 482, New York, NY 10021, USA
    Expert Opin Ther Targets 10:37-50. 2006
  10. ncbi request reprint Purine-scaffold Hsp90 inhibitors
    Gabriela Chiosis
    Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    IDrugs 9:778-82. 2006

Research Grants

Collaborators

Detail Information

Publications56

  1. ncbi request reprint Emerging Hsp90 inhibitors: from discovery to clinic
    G Chiosis
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Anticancer Agents Med Chem 6:1-8. 2006
    ..This review intends to update the reader on the status of several existing and emerging classes of direct inhibitors of Hsp90 ATPase activity...
  2. pmc Assay strategies for the discovery and validation of therapeutics targeting Brugia pahangi Hsp90
    Tony Taldone
    Department of Molecular Pharmacology and Chemistry, Sloan Kettering Institute, New York, New York, United States of America
    PLoS Negl Trop Dis 4:e714. 2010
    ..The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target...
  3. pmc A purine scaffold Hsp90 inhibitor destabilizes BCL-6 and has specific antitumor activity in BCL-6-dependent B cell lymphomas
    Leandro C Cerchietti
    Division of Hematology and Oncology, Weill Cornell Medical College of Cornell University, New York, New York, USA
    Nat Med 15:1369-76. 2009
    ..PU-H71 also induced cell death in primary human DLBCL specimens...
  4. ncbi request reprint Regulatory chaperone complexes in neurodegenerative diseases: a perspective on therapeutic intervention
    Aaron Carman
    Molecular Pharmacology and Chemistry, Sloan Kettering Institute, Associate Attending, Breast Cancer Service, Department of Medicine, Memorial Hospital, Memorial Sloan Kettering Cancer Center, ZRB2103, Associate Professor, Weill Graduate School of Medical Sciences, New York, USA
    Curr Alzheimer Res 11:59-68. 2014
    ..Here we discuss how chaperone interactions and small molecule inhibitors can regulate the burden of aberrant client signaling in these neurological disorders. ..
  5. pmc Heat shock protein 90: translation from cancer to Alzheimer's disease treatment?
    Wenjie Luo
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University and Fisher Foundation for Alzheimer s Disease, New York, NY 10021, USA
    BMC Neurosci 9:S7. 2008
    ..It will present experimentally demonstrated, but also hypothetical, roles that suggest Hsp90 can act as a regulator of pathogenic changes that lead to the neurodegenerative phenotype in Alzheimer's disease...
  6. ncbi request reprint Discovery and development of purine-scaffold Hsp90 inhibitors
    Gabriela Chiosis
    Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Curr Top Med Chem 6:1183-91. 2006
    ..One such emerging class is the purine-scaffold series. This review intends to inform the reader on efforts ranging from the discovery to their clinical translation...
  7. ncbi request reprint Hsp90: the vulnerable chaperone
    Gabriela Chiosis
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Drug Discov Today 9:881-8. 2004
    ..This review will discuss several emerging classes of Hsp90 inhibitors and their modes of action...
  8. ncbi request reprint Small molecule microarrays: from proteins to mammalian cells - are we there yet?
    Gabriela Chiosis
    Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Trends Biotechnol 23:271-4. 2005
    ..This technological improvement opens the door for using SMMs to perform high-throughput screens in mammalian cells...
  9. ncbi request reprint Targeting chaperones in transformed systems--a focus on Hsp90 and cancer
    Gabriela Chiosis
    Programme in Molecular Pharmacology and Chemistry, Department of Medicine, Memorial Sloan Kettering Cancer Center, Box 482, New York, NY 10021, USA
    Expert Opin Ther Targets 10:37-50. 2006
    ..In this review, the authors present the current understanding on the relevance and possibility of translating Hsp90 inhibitors into therapeutic agents in cancer therapy...
  10. ncbi request reprint Purine-scaffold Hsp90 inhibitors
    Gabriela Chiosis
    Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    IDrugs 9:778-82. 2006
    ..This feature describes the purine-scaffold class of Hsp90 inhibitors, focusing on research efforts from the discovery stage to the clinical translation of such compounds...
  11. ncbi request reprint Synthesis of Hsp90 dimerization modulators
    Gabriela Chiosis
    Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Bioorg Med Chem Lett 16:3529-32. 2006
    ..These agents may represent useful tools to study the importance of N-terminal dimerization and also to determine subunit interface(s) in Hsp90...
  12. ncbi request reprint Heat shock protein-90 inhibitors: a chronicle from geldanamycin to today's agents
    Gabriela Chiosis
    Memorial Sloan Kettering Cancer Center, Department of Medicine and Program in Molecular Pharmacology and Chemistry, 1275 York Avenue, New York, NY 10021, USA
    Curr Opin Investig Drugs 7:534-41. 2006
    ..This review discusses the modalities that may interfere with this chaperone's function and describes the status of existing and emerging Hsp90 inhibitor classes...
  13. ncbi request reprint 17AAG: low target binding affinity and potent cell activity--finding an explanation
    Gabriela Chiosis
    Program in Cell Biology and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Mol Cancer Ther 2:123-9. 2003
    ..We suggest that in the clinic, micromolar concentrations of 17AAG must accumulate in the tumor cells to achieve antitumor effects in patients comparable with ones achieved in tissue culture settings...
  14. ncbi request reprint Development of purine-scaffold small molecule inhibitors of Hsp90
    Gabriela Chiosis
    Department of Medicine and Cell Biology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Curr Cancer Drug Targets 3:371-6. 2003
    ..The development of novel agents that lack the drawbacks of the natural products is thus necessary. Here we present an overview of such efforts with focus on a new class of purine-scaffold Hsp90 inhibitors developed by rational design...
  15. pmc Heat shock protein 90 in neurodegenerative diseases
    Wenjie Luo
    Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Mol Neurodegener 5:24. 2010
    ..This mini-review will summarize our current knowledge on Hsp90 in neurodegeneration and will focus on the potential beneficial application of Hsp90 inhibitors in neurodegenerative diseases...
  16. ncbi request reprint Identification of a geldanamycin dimer that induces the selective degradation of HER-family tyrosine kinases
    F F Zheng
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Cancer Res 60:2090-4. 2000
    ..GMD-4c could be useful in the treatment of carcinomas dependent on HER-kinases...
  17. ncbi request reprint A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells
    G Chiosis
    Program in Cell Biology and Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Chem Biol 8:289-99. 2001
    ..e. steroid receptors, Her2, Raf). We have used the structural features of this pocket to design a small molecule inhibitor of Hsp90...
  18. ncbi request reprint Targeting wide-range oncogenic transformation via PU24FCl, a specific inhibitor of tumor Hsp90
    Maria Vilenchik
    Program in Cell Biology and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021 USA
    Chem Biol 11:787-97. 2004
    ..Concentrations achieved in vivo in tumors lead to single-agent anti-tumor activity at non-toxic doses...
  19. ncbi request reprint Total synthesis as a resource in the discovery of potentially valuable antitumor agents: cycloproparadicicol
    Kana Yamamoto
    Laboratory for Bioorganic Chemistry, Sloan Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10021, USA
    Angew Chem Int Ed Engl 42:1280-4. 2003
  20. ncbi request reprint LY294002-geldanamycin heterodimers as selective inhibitors of the PI3K and PI3K-related family
    G Chiosis
    Department of Molecular Oncogenesis, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Bioorg Med Chem Lett 11:909-13. 2001
    ..Several LY294002-GM heterodimers were synthesized with the intent of modulating their activity in the presence of hsp90 and thereby creating selective inhibitors of PI3K and PI3K-related family...
  21. ncbi request reprint Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase
    Gabriela Chiosis
    Program in Cell Biology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Bioorg Med Chem 10:3555-64. 2002
    ..Induces the degradation of Her2 tyrosine kinase and arrests the MCF-7 breast cancer cell line at low micromolar concentrations (IC50=2 microM)...
  22. ncbi request reprint Evaluation of 8-arylsulfanyl, 8-arylsulfoxyl, and 8-arylsulfonyl adenine derivatives as inhibitors of the heat shock protein 90
    Laura Llauger
    Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Med Chem 48:2892-905. 2005
    ....
  23. ncbi request reprint Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer
    Anna Rodina
    Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    Nat Chem Biol 3:498-507. 2007
    ..These results provide important evidence for a transformation-specific interplay between chaperones in regulating apoptosis in malignant cells...
  24. ncbi request reprint Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function
    Andrea D Basso
    Program in Pharmacology, Weill Graduate School of Medical Sciences, Cornell University and the Program in Cell Biology and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Biol Chem 277:39858-66. 2002
    ..Thus, transduction of growth factor signaling via the Akt and Raf pathways requires functional Hsp90 and can be coordinately blocked by its inhibition...
  25. pmc Hsp90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models
    Eloisi Caldas-Lopes
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 106:8368-73. 2009
    ..The results identify Hsp90 as a critical and multimodal target in this most difficult to treat breast cancer subtype and support the use of the Hsp90 inhibitor PU-H71 for clinical trials involving patients with TNBC...
  26. pmc Assay for isolation of inhibitors of her2-kinase expression
    Gabriela Chiosis
    Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY, USA
    Methods Mol Biol 486:139-49. 2009
    ..Here, we describe a hybrid western-blotting and enzyme-linked immunosorbent assay (ELISA) designed to identify in low- to medium-throughput format noncytotoxic compounds that reduce expression of Her2 protein...
  27. pmc Targeting Hsp90: small-molecule inhibitors and their clinical development
    Tony Taldone
    Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Curr Opin Pharmacol 8:370-4. 2008
    ....
  28. ncbi request reprint Synthesis of a red-shifted fluorescence polarization probe for Hsp90
    Kamalika Moulick
    Program in Molecular Pharmacology and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Bioorg Med Chem Lett 16:4515-8. 2006
    ..The synthesis of a red-shifted cy3B-GM ligand and its evaluation as a fluorescence polarization probe for Hsp90 is presented...
  29. ncbi request reprint Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90
    Huazhong He
    Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Med Chem 49:381-90. 2006
    ..When administered in vivo to mice bearing MDA-MB-468 human breast cancer xenografted tumors, these agents result in pharmacologically relevant concentrations and, accordingly, in modulation of Hsp90-client proteins in tumors...
  30. ncbi request reprint Purine-scaffold Hsp90 inhibitors
    Tony Taldone
    Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Curr Top Med Chem 9:1436-46. 2009
    ..Their potential towards neurodegenerative diseases will also be touched upon...
  31. ncbi request reprint Synthesis of novel fluorescent probes for the molecular chaperone Hsp90
    Laura Llauger-Bufi
    Program in Cell Biology and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Bioorg Med Chem Lett 13:3975-8. 2003
    ..Here we report the synthesis and characterization of two fluorescent Hsp90 inhibitors and probe their use in an Hsp90 fluorescent polarization assay...
  32. ncbi request reprint Development of a fluorescence polarization assay for the molecular chaperone Hsp90
    Joungnam Kim
    Program in Cell Biology and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Biomol Screen 9:375-81. 2004
    ..These data demonstrate that the Hsp90-FP-based assay can be used for high-throughput screening in aiding the identification of novel Hsp90 inhibitors...
  33. doi request reprint Development and application of Hsp90 inhibitors
    David B Solit
    Department of Medicine and the Human Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, United States
    Drug Discov Today 13:38-43. 2008
    ..It will also update the reader on the preclinical development and clinical translation of Hsp90 inhibitors...
  34. ncbi request reprint Selective cleavage of D-Ala-D-Lac by small molecules: re-sensitizing resistant bacteria to vancomycin
    G Chiosis
    Department of Chemistry, Columbia University, New York, NY 10027, USA
    Science 293:1484-7. 2001
    ..These molecules were tested in combination with vancomycin and were found to re-sensitize vancomycin-resistant bacteria to the antibiotic...
  35. pmc Discovery and development of heat shock protein 90 inhibitors
    Tony Taldone
    Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 482, New York, NY 10021, USA
    Bioorg Med Chem 17:2225-35. 2009
    ..This review will discuss the discovery of these different classes, as well as their development as potential clinical agents...
  36. ncbi request reprint General method for the synthesis of 8-arylsulfanyl adenine derivatives
    Huazhong He
    Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    J Org Chem 69:3230-2. 2004
    ..We report a general method for the synthesis of 8-arylsulfanyl adenine derivatives using a mild protocol of coupling 8-mercaptoadenine with a variety of aryl iodides...
  37. pmc Measuring the pharmacodynamic effects of a novel Hsp90 inhibitor on HER2/neu expression in mice using Zr-DFO-trastuzumab
    Jason P Holland
    Radiochemistry Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, Sloan Kettering Cancer Center, New York, New York, United States of America
    PLoS ONE 5:e8859. 2010
    ..In addition, pharmacodynamic studies on HER2/neu expression levels in response to therapeutic doses of PU-H71 (a specific inhibitor of heat-shock protein 90 [Hsp90]) were conducted...
  38. ncbi request reprint Tumor selectivity of Hsp90 inhibitors: the explanation remains elusive
    Gabriela Chiosis
    Department of Medicine and Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA
    ACS Chem Biol 1:279-84. 2006
    ..They spotlight the higher affinity of ansamycins' hydroquinone over the quinone form for Hsp90 and further discuss its possible contribution to ansamycins' tumor selectivity...
  39. pmc HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans
    Sachie Marubayashi
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    J Clin Invest 120:3578-93. 2010
    ..Importantly, PU-H71 treatment also reduced the mutant allele burden in mice. These data establish what we believe to be a novel therapeutic rationale for HSP90 inhibition in the treatment of JAK2-dependent MPN...
  40. pmc Microwave-assisted one step synthesis of 8-arylmethyl-9H-purin-6-amines
    Hui Tao
    Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Box 482, New York, NY 10021, USA
    Bioorg Med Chem Lett 19:415-7. 2009
    ..We discuss the applicability as well as the limitations of this method towards the creation of a large chemical diversity in the 8-arylmethyl-9H-purin-6-amine series...
  41. pmc Roles of heat-shock protein 90 in maintaining and facilitating the neurodegenerative phenotype in tauopathies
    Wenjie Luo
    Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University and Fisher Foundation for Alzheimer s Disease, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 104:9511-6. 2007
    ..The results identify important roles played by Hsp90 in maintaining and facilitating the degenerative phenotype in these diseases and provide a common principle governing cancer and neurodegenerative diseases...
  42. doi request reprint Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines
    Eloisi C Lopes
    Department of Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Cancer Res 68:7258-63. 2008
    ..Because Kaiso inactivation sensitized colon cancer cell lines to chemotherapy, it is possible that therapeutic targeting of Kaiso could improve the efficacy of current treatment regimens...
  43. ncbi request reprint Microtiter cell-based assay for detection of agents that alter cellular levels of Her2 and EGFR
    Henri Huezo
    Program in Cell Biology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Chem Biol 10:629-34. 2003
    ..The method gives results comparable to Western blot, but it is faster, less labor intensive, and amenable to high throughput...
  44. pmc Design of a fluorescence polarization assay platform for the study of human Hsp70
    Yanlong Kang
    Program in Molecular Pharmacology and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Bioorg Med Chem Lett 18:3749-51. 2008
    ..Here, we present a novel assay platform based on fluorescence polarization that is suitable for investigating the yet elusive molecular mechanics of human Hsp70 allosteric regulation...
  45. ncbi request reprint Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators
    Haley Hieronymus
    The Broad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
    Cancer Cell 10:321-30. 2006
    ..Validating this prediction, we demonstrate that celastrol and gedunin inhibit HSP90 activity and HSP90 clients, including AR. Broadly, this work identifies new modes of HSP90 modulation through a gene expression-based strategy...
  46. ncbi request reprint Anti-cancer therapeutic approaches based on intracellular and extracellular heat shock proteins
    Celine Didelot
    Inserm UMR 866, Faculty of Medicine and Pharmacy, 7 Boulevard Jeanne d Arc, 21049 Dijon, France
    Curr Med Chem 14:2839-47. 2007
    ..This review will discuss this different and often paradoxical approaches in cancer therapy based on the dual role of Hsps, protective/tumorigenic versus immunogenic...
  47. pmc Molecular imaging of the efficacy of heat shock protein 90 inhibitors in living subjects
    Carmel T Chan
    Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 5427, USA
    Cancer Res 68:216-26. 2008
    ....
  48. pmc Identification of novel quaternary domain interactions in the Hsp90 chaperone, GRP94
    Feixia Chu
    Mass Spectrometry Facility, University of California, San Francisco, California 94143, USA
    Protein Sci 15:1260-9. 2006
    ..These results identify a compact, intertwined quaternary conformation of native GRP94 and suggest that intersubunit N+M interactions are integral to the structural biology of Hsp90...
  49. ncbi request reprint Structural and quantum chemical studies of 8-aryl-sulfanyl adenine class Hsp90 inhibitors
    Robert M Immormino
    Hauptman Woodward Medical Research Institute, Buffalo, New York 14203, USA
    J Med Chem 49:4953-60. 2006
    ..The predictive nature of the calculations has allowed the exploration of additional derivatives based on the 8-aryl adenine scaffold...
  50. pmc The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2
    Lizhen Wang
    Unit of Transgenesis, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland 20892, USA
    J Neurosci 28:3384-91. 2008
    ..Therefore, inhibition of LRRK2 kinase activity can be achieved by blocking Hsp90-mediated chaperone activity and Hsp90 inhibitors may serve as potential anti-PD drugs...
  51. ncbi request reprint Hsp70 molecular chaperones: emerging roles in human disease and identification of small molecule modulators
    Jeffrey L Brodsky
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260 USA
    Curr Top Med Chem 6:1215-25. 2006
    ..Finally, we will review the recent discovery of small molecules that alter Hsp70 expression and function...
  52. ncbi request reprint New arylthioindoles: potent inhibitors of tubulin polymerization. 2. Structure-activity relationships and molecular modeling studies
    Gabriella De Martino
    Istituto Pasteur Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Universita di Roma La Sapienza, Piazzale Aldo Moro 5, I 00185 Rome, Italy
    J Med Chem 49:947-54. 2006
    ..Dynamics simulation studies correlate well with the observed experimental data. Furthermore, from careful analysis of the biological and in silico data, we can now hypothesize a basic pharmacophore for this class of compounds...
  53. ncbi request reprint Vancomycin resistance: occurrence, mechanisms and strategies to combat it
    Ivo G Boneca
    Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, 25 28 Rue du Docteur Roux, 75724 Paris Cedex 15, France
    Expert Opin Ther Targets 7:311-28. 2003
    ..Whilst most of these agents are still in clinical or preclinical development, some have entered the clinic and currently represent the only option for treating vancomycin-resistant enterococci (VRE)...
  54. ncbi request reprint BCR-ABL point mutants isolated from patients with imatinib mesylate-resistant chronic myeloid leukemia remain sensitive to inhibitors of the BCR-ABL chaperone heat shock protein 90
    Mercedes E Gorre
    Department of Medicine and Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, CA 900095 1678, USA
    Blood 100:3041-4. 2002
    ..These data support clinical investigations of 17-AAG in imatinib mesylate-resistant Ph(+) leukemias...
  55. ncbi request reprint High-throughput screening fluorescence polarization assay for tumor-specific Hsp90
    Yuhong Du
    Department of Pharmacology, Emory University School of Medicine and Emory Chemical Biology Discovery Center, Atlanta, Georgia, USA
    J Biomol Screen 12:915-24. 2007
    ..A study using more than 15,000 compounds from the National Institutes of Health Molecular Libraries Screening Center Network was performed to validate its performance in a high-throughput screening format...
  56. pmc Discovery of aminoquinolines as a new class of potent inhibitors of heat shock protein 90 (Hsp90): Synthesis, biology, and molecular modeling
    Thota Ganesh
    Chemical Biology Discovery Center, 1510 Clifton Road, Emory University, Atlanta, GA 30322, USA
    Bioorg Med Chem 16:6903-10. 2008
    ..These compounds represent a new class of Hsp90 inhibitors with simple chemical structures...

Research Grants8

  1. Development of HTS assays probing Hsp90 inhibition (RMI)
    Gabriela Chiosis; Fiscal Year: 2004
    ..Hits resulted from the FP assay will be tested for Her2 degradation potency in the breast cancer cell line SKBr3. Highest ranking compounds in both screens will be taken for further testing in follow-up research programs. ..
  2. Assays for rapid identification of Hsp70 modulators
    Gabriela Chiosis; Fiscal Year: 2006
    ....
  3. Isolation of Inhibitors of Her-Kinase Expression (RMI)
    Gabriela Chiosis; Fiscal Year: 2005
    ..To our knowledge, this has not been accomplished, and we believe that we are uniquely positioned to initiate this goal. ..
  4. FP Assay for Isolation of Hsp90 Inhibitors (RMI)
    Gabriela Chiosis; Fiscal Year: 2005
    ....
  5. Assays for rapid identification of Hsp70 modulators
    Gabriela Chiosis; Fiscal Year: 2007
    ....
  6. Hsp90 inhibitors as suppressors of protein misfolding toxicity
    Gabriela Chiosis; Fiscal Year: 2007
    ..In conclusion, Hsp90- interfering drugs represent a potential novel class of drugs to promote the survival of neurons and open up a promising approach to the treatment of neurodegenerative diseases. ..