benzoquinones

Summary

Summary: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.

Top Publications

  1. ncbi Thymoquinone: a promising anti-cancer drug from natural sources
    Hala Gali-Muhtasib
    Department of Biology, American University of Beirut, Beirut, Lebanon
    Int J Biochem Cell Biol 38:1249-53. 2006
  2. ncbi Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1
    J Zou
    Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Florida 33101, USA
    Cell 94:471-80. 1998
  3. ncbi HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab
    Shanu Modi
    Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Clin Cancer Res 17:5132-9. 2011
  4. ncbi Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone
    Rongmin Zhao
    Department of Biochemistry, Medical Sciences Building, 1 King s College Circle, University of Toronto, Toronto, ON, M5S 1A8, Canada
    Cell 120:715-27. 2005
  5. ncbi Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosis
    Marissa V Powers
    Signal Transduction and Molecular Pharmacology Team, Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey SM2 5NG, UK
    Cancer Cell 14:250-62. 2008
  6. 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
  7. pmc RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha
    Ye V Liu
    Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Mol Cell 25:207-17. 2007
  8. ncbi Altered Hsp90 function in cancer: a unique therapeutic opportunity
    Rochelle Bagatell
    Department of Pediatrics and Hematology Oncology, Arizona Health Sciences Center, Room 5341, 1501 North Campbell Avenue, Tucson, AZ 85724, USA
    Mol Cancer Ther 3:1021-30. 2004
  9. ncbi Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent
    C E Stebbins
    Department of Biochemistry and Structural Biology, Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA
    Cell 89:239-50. 1997
  10. pmc Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug
    Rani Pallavi
    Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India
    J Biol Chem 285:37964-75. 2010

Research Grants

  1. Novel Mechanisms of Quinone Toxicity
    David Ross; Fiscal Year: 2013
  2. Arthropod-Based Libraries for High Throughput Screening
    Frank Schroeder; Fiscal Year: 2009
  3. SYNTHESIS OF BIOLOGICALLY IMPORTANT DIHYDROBENZOFURANS
    Thomas Engler; Fiscal Year: 1991
  4. SECRETIONS OF ARTHROPODS
    Thomas Eisner; Fiscal Year: 2008
  5. PROTON & ELECTRON TRANSFER & ENERGY COUPLING IN SITE I
    TOMOKO NONE OHNISHI; Fiscal Year: 2010
  6. FP Assay for Isolation of Hsp90 Inhibitors (RMI)
    Gabriela Chiosis; Fiscal Year: 2005
  7. Isolation of Inhibitors of Her-Kinase Expression (RMI)
    Gabriela Chiosis; Fiscal Year: 2005
  8. Assays for rapid identification of Hsp70 modulators
    Gabriela Chiosis; Fiscal Year: 2008
  9. Hsp90 inhibitors as suppressors of protein misfolding toxicity
    Gabriela Chiosis; Fiscal Year: 2008
  10. Regulation of Lung Epithelial Fibrinolysis by Urokinase
    Sreerama Shetty; Fiscal Year: 2005

Detail Information

Publications303 found, 100 shown here

  1. ncbi Thymoquinone: a promising anti-cancer drug from natural sources
    Hala Gali-Muhtasib
    Department of Biology, American University of Beirut, Beirut, Lebanon
    Int J Biochem Cell Biol 38:1249-53. 2006
    ..The combination of TQ with clinically used anti-cancer drugs has led to improvements in their therapeutic index and prevents non-tumor tissues from sustaining chemotherapy-induced damage...
  2. ncbi Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1
    J Zou
    Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Florida 33101, USA
    Cell 94:471-80. 1998
    ..Hsp90-containing HSF1 complex is present in the unstressed cell and dissociates during stress. We conclude that Hsp90, by itself and/or associated with multichaperone complexes, is a major repressor of HSF1...
  3. ncbi HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab
    Shanu Modi
    Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Clin Cancer Res 17:5132-9. 2011
    ..On the basis of these data and activity in a phase I study, we conducted a phase II study of 17-AAG (tanespimycin) with trastuzumab in advanced trastuzumab-refractory HER2-positive breast cancer...
  4. ncbi Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperone
    Rongmin Zhao
    Department of Biochemistry, Medical Sciences Building, 1 King s College Circle, University of Toronto, Toronto, ON, M5S 1A8, Canada
    Cell 120:715-27. 2005
    ..These cofactors interact physically and functionally with the conserved AAA(+)-type DNA helicases Rvb1/Rvb2, which are key components of several chromatin remodeling factors, thereby linking Hsp90 to epigenetic gene regulation...
  5. ncbi Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosis
    Marissa V Powers
    Signal Transduction and Molecular Pharmacology Team, Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey SM2 5NG, UK
    Cancer Cell 14:250-62. 2008
    ..Importantly, simultaneous silencing of HSP70 isoforms in nontumorigenic cell lines does not result in comparable growth arrest or induction of apoptosis, indicating a potential therapeutic window...
  6. 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
    ....
  7. pmc RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alpha
    Ye V Liu
    Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Mol Cell 25:207-17. 2007
    ..Thus, RACK1 is an essential component of an O(2)/PHD/VHL-independent mechanism for regulating HIF-1alpha stability through competition with HSP90 and recruitment of the Elongin-C/B ubiquitin ligase complex...
  8. ncbi Altered Hsp90 function in cancer: a unique therapeutic opportunity
    Rochelle Bagatell
    Department of Pediatrics and Hematology Oncology, Arizona Health Sciences Center, Room 5341, 1501 North Campbell Avenue, Tucson, AZ 85724, USA
    Mol Cancer Ther 3:1021-30. 2004
    ....
  9. ncbi Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent
    C E Stebbins
    Department of Biochemistry and Structural Biology, Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA
    Cell 89:239-50. 1997
    ..This, and the pocket's similarity to substrate-binding sites, suggest that the pocket binds a portion of the polypeptide substrate and participates in the conformational maturation/refolding reaction...
  10. pmc Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drug
    Rani Pallavi
    Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India
    J Biol Chem 285:37964-75. 2010
    ..evansi growth in a mouse model of trypanosomiasis. In all, our biochemical characterization, drug interaction, and animal studies supported Hsp90 as a drug target and its inhibitor as a potential drug against protozoan diseases...
  11. ncbi Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling
    Nahed El-Najjar
    Department of Biology, American University of Beirut, Beirut, Lebanon
    Apoptosis 15:183-95. 2010
    ..These data present evidence linking the pro-oxidant effects of TQ with its apoptotic effects in colon cancer and prove a protective role of MAPK...
  12. pmc Heat shock transcription factor 1-activating compounds suppress polyglutamine-induced neurodegeneration through induction of multiple molecular chaperones
    Nobuhiro Fujikake
    Division of Clinical Genetics, Department of Medical Genetics, Osaka University Graduate School of Medicine, Suita, Osaka 565 0871, Japan
    J Biol Chem 283:26188-97. 2008
    ..Our study indicates that induction of multiple molecular chaperones by 17-AAG treatment is a promising therapeutic approach for a wide range of polyQ diseases and possibly other neurodegenerative diseases...
  13. ncbi Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy
    Weiwen Ying
    Synta Pharmaceuticals Corp, 45 Hartwell Avenue, Lexington, MA 02421, USA
    Mol Cancer Ther 11:475-84. 2012
    ....
  14. ncbi The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target
    Melissa L Fishel
    Department of Pediatrics Section of Hematology Oncology, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, United States
    Mol Aspects Med 28:375-95. 2007
    ..In this review, we will provide an overview of Ape1/Ref-1's activities and explore the potential of this protein as a target in cancer treatment as well as its role in chemoprevention...
  15. ncbi Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes
    Gowrishankar Banumathy
    Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India
    J Biol Chem 278:18336-45. 2003
    ..In addition to suggesting an essential role for PfHsp90 during parasite growth, our results highlight PfHsp90 as a potential drug target to control malaria...
  16. ncbi Inhibition of heat shock protein 90 (HSP90) as a therapeutic strategy for the treatment of myeloma and other cancers
    Paul G Richardson
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    Br J Haematol 152:367-79. 2011
    ....
  17. ncbi Gene and protein expression profiling of human ovarian cancer cells treated with the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin
    Alison Maloney
    Haddow Laboratories, Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Surrey, United Kingdom
    Cancer Res 67:3239-53. 2007
    ....
  18. ncbi Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilization
    Y Peng
    Molecular Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
    J Biol Chem 276:40583-90. 2001
    ..These results suggest that hsp90 recruited by mutant p53 conceals the ARF-binding site on MDM2 and inhibits its ubiquitin-protein isopeptide ligase function, resulting in the stabilization of both mutant p53 and MDM2...
  19. pmc Evolutionary constraints on chaperone-mediated folding provide an antiviral approach refractory to development of drug resistance
    Ron Geller
    Department of Biological Sciences, Stanford University, Stanford, California 94305, USA
    Genes Dev 21:195-205. 2007
    ..We propose that targeting folding of viral proteins may provide a general antiviral strategy that is refractory to development of drug resistance...
  20. ncbi Anticancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR-γ pathway
    Chern Chiuh Woo
    Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    Biochem Pharmacol 82:464-75. 2011
    ....
  21. pmc Potent activity of the Hsp90 inhibitor ganetespib in prostate cancer cells irrespective of androgen receptor status or variant receptor expression
    Suqin He
    Synta Pharmaceuticals Corp, Lexington, MA 02421, USA
    Int J Oncol 42:35-43. 2013
    ..Together these data suggest that further investigation of ganetespib as a new therapeutic treatment for prostate cancer patients is warranted...
  22. ncbi Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity
    Kheem S Bisht
    Radiation Oncology Branch and Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 1002, USA
    Cancer Res 63:8984-95. 2003
    ..This work shows that altered HSP90 function induces significant tumor cytotoxicity and radiosensitization, suggesting a potential therapeutic utility...
  23. ncbi Plasma pharmacokinetics and tissue distribution of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) in CD2F1 mice1
    M J Egorin
    Division of Developmental Therapeutics, University of Maryland Cancer Center, Baltimore, MD 21201, USA
    Cancer Chemother Pharmacol 47:291-302. 2001
    ..v., i.p., or orally. 17AAG is widely distributed to tissues. These pharmacokinetic data generated have proven relevant to the design of recently initiated clinical trials of 17AAG and could be useful in their interpretation...
  24. pmc V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors
    O M Grbovic
    Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 103:57-62. 2006
    ..Hsp90 inhibition represents a therapeutic strategy for the treatment of melanoma...
  25. pmc Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma
    Subhasis Das
    School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal, India
    PLoS ONE 7:e46641. 2012
    ..TQ and DG, alone and in combination, inhibit cell proliferation and induce apoptosis in squamous cell carcinoma. The combination of TQ and DG is a potential antineoplastic therapy in this common skin cancer...
  26. ncbi Thymoquinone: potential cure for inflammatory disorders and cancer
    Chern Chiuh Woo
    Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
    Biochem Pharmacol 83:443-51. 2012
    ..In this review, we summarize the anti-oxidant/anti-inflammatory and anticancer effects of thymoquinone with a focus on its molecular targets, and its possible role in the treatment of inflammatory diseases and cancer...
  27. ncbi Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumor
    Sebastian Bauer
    Department of Pathology, Brigham and Women s Hospital, Center for Sarcoma and Bone Oncology, Dana Farber Cancer Institute, and Ludwig Center at Dana Farber Harvard Cancer Center, Boston, Massachusetts 02115, USA
    Cancer Res 66:9153-61. 2006
    ..The dramatic inactivation of imatinib-resistant KIT oncoproteins suggests that HSP90 inhibition provides a therapeutic solution to the challenge of heterogeneous imatinib resistance mutations in GIST patients...
  28. ncbi 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration
    Masahiro Waza
    Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai Cho, Showa Ku, Nagoya 466 8550, Japan
    Nat Med 11:1088-95. 2005
    ..17-AAG also mildly induced Hsp70 and Hsp40. 17-AAG would thus provide a new therapeutic approach to SBMA and probably to other related neurodegenerative diseases...
  29. ncbi A novel HSP90 inhibitor delays castrate-resistant prostate cancer without altering serum PSA levels and inhibits osteoclastogenesis
    Francois Lamoureux
    The Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada
    Clin Cancer Res 17:2301-13. 2011
    ..17-Allylamino-17-demethoxy-geldanamycin (17-AAG) has been reported to inhibit tumor growth in various cancers; however, it induces tumor progression in the bone microenvironment...
  30. ncbi Pharmacokinetic-pharmacodynamic relationships for the heat shock protein 90 molecular chaperone inhibitor 17-allylamino, 17-demethoxygeldanamycin in human ovarian cancer xenograft models
    Udai Banerji
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, United Kingdom
    Clin Cancer Res 11:7023-32. 2005
    ..To establish the pharmacokinetic and pharmacodynamic profile of the heat shock protein 90 (HSP90) inhibitor 17-allylamino, 17-demethoxygeldanamycin (17-AAG) in ovarian cancer xenograft models...
  31. ncbi Hsp90 inhibition has opposing effects on wild-type and mutant p53 and induces p21 expression and cytotoxicity irrespective of p53/ATM status in chronic lymphocytic leukaemia cells
    K Lin
    Department of Haematology, Royal Liverpool and Broadgreen University Hospitals Trust, Liverpool, UK
    Oncogene 27:2445-55. 2008
    ..In summary, our findings reveal important consequences of inhibiting Hsp90 in CLL cells and strongly support the therapeutic evaluation of Hsp90 inhibitors in poor-prognosis patients with p53 defects...
  32. ncbi Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycin
    Silvy da Rocha Dias
    The Institute of Cancer Research, Signal Transduction Team, Cancer Research UK Centre for Cell and Molecular Biology, London, United Kingdom
    Cancer Res 65:10686-91. 2005
    ..Our data show that B-RAF is an important target for 17-AAG in human cancer...
  33. ncbi Targeting nuclear factor-kappa B activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis
    Gautam Sethi
    Cytokine Research Laboratory, Department of Experimental Therapeutics, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Mol Cancer Res 6:1059-70. 2008
    ....
  34. ncbi Pharmacological and toxicological properties of Nigella sativa
    B H Ali
    Department of Veterinary Medicine, King Saud University, Buraydah, Al Gaseem 81999, Saudi Arabia
    Phytother Res 17:299-305. 2003
    ..It would appear that the beneficial effects of the use of the seeds and thymoquinone might be related to their cytoprotective and antioxidant actions, and to their effect on some mediators of inflammation...
  35. ncbi Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG
    Eckhard Ficker
    Rammelkamp Center, Case Western Reserve University, Cleveland, Ohio 44109, USA
    Circ Res 92:e87-100. 2003
    ..We conclude that Hsp90 and Hsp70 are crucial for the maturation of hERG WT as well as the retention of trafficking-deficient LQT2 mutants. The full text of this article is available online at http://www.circresaha.org...
  36. ncbi Hsp90 inhibitors as novel cancer chemotherapeutic agents
    Len Neckers
    Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, 9610 Medical Center Drive, Suite 300, Rockville, MD 20850, USA
    Trends Mol Med 8:S55-61. 2002
    ..Because of the chemoprotective activity of several proteins that are Hsp90 clients, the combination of an Hsp90 inhibitor with a standard chemotherapeutic agent could dramatically increase the in vivo efficacy of the therapeutic agent...
  37. ncbi Hsp90 inhibitors suppress HCV replication in replicon cells and humanized liver mice
    Shin Ichiro Nakagawa
    Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3 18 22 Honkomagome, Bunkyo ku, Tokyo 113 8613, Japan
    Biochem Biophys Res Commun 353:882-8. 2007
    ..These results suggest that inhibition of Hsp90 could provide a new therapeutic approach to HCV infection...
  38. pmc In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis
    W M Obermann
    Department of Cellular Biochemistry, Max Planck Institut fur Biochemie, D 82152 Martinsried, Germany
    J Cell Biol 143:901-10. 1998
    ..Our results establish Hsp90 as an ATP-dependent chaperone...
  39. pmc Ansamycin antibiotics inhibit Akt activation and cyclin D expression in breast cancer cells that overexpress HER2
    Andrea D Basso
    Program in Pharmacology, Weill Graduate School of Medical Sciences, Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Oncogene 21:1159-66. 2002
    ..Thus, pharmacological inhibition of Akt activation is achievable with ansamycins and may be useful for the treatment of HER2 driven tumors...
  40. pmc A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer
    Elisabeth I Heath
    Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA
    Clin Cancer Res 14:7940-6. 2008
    ..A two-stage phase II study was conducted to assess the activity and toxicity profile of 17-AAG administered to patients with metastatic, hormone-refractory prostate cancer...
  41. ncbi 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts
    David B Solit
    Program in Cell Biology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 8:986-93. 2002
    ....
  42. ncbi Inhibitors of the HSP90 molecular chaperone: current status
    Swee Sharp
    Signal Transduction and Molecular Pharmacology Team, Cancer Research UK, Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, SM2 5NG, United Kingdom
    Adv Cancer Res 95:323-48. 2006
    ..Thus, it is not surprising that new HSP90 agents are under development against this novel target for cancer therapy and several show promise...
  43. ncbi Thymoquinone triggers inactivation of the stress response pathway sensor CHEK1 and contributes to apoptosis in colorectal cancer cells
    Hala Gali-Muhtasib
    Department of Biology, American University of Beirut, Beirut, Lebanon
    Cancer Res 68:5609-18. 2008
    ..9-fold risk, univariate Cox regression; Kaplan-Meier, P = 0.04). We suggest that the inhibition of the stress response sensor CHEK1 might contribute to the antineoplastic activity of specific DNA-damaging drugs...
  44. ncbi Inhibition of hsp90 compromises the DNA damage response to radiation
    Hideaki Dote
    Molecular Radiation Therapeutics and Radiation Oncology Branches, National Cancer Institute, Bethesda, Maryland
    Cancer Res 66:9211-20. 2006
    ..These data indicate that Hsp90 can contribute to the DNA damage response to radiation affecting both DNA repair and cell cycle checkpoint activation...
  45. ncbi Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycins
    Takeshi Shimamura
    Lowe Center for Thoracic Oncology and Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Res 65:6401-8. 2005
    ..These data suggest mutational activation of EGFR is associated with dependence on Hsp90 for stability and that Hsp90 inhibition may represent a novel strategy for the treatment of EGFR-mutant NSCLC...
  46. ncbi Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism
    Hala Gali-Muhtasib
    Department of Biology, American University of Beirut, Beirut, Lebanon
    Int J Oncol 25:857-66. 2004
    ..The apoptotic effects of TQ are modulated by Bcl-2 protein and are linked to and dependent on p53. Our data support the potential for using the agent TQ for the treatment of colon cancer...
  47. ncbi Hsp90 inhibitors reduce influenza virus replication in cell culture
    Geoffrey Chase
    Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Hermann Herder Strasse 11, D 79104 Freiburg, Germany
    Virology 377:431-9. 2008
    ..Hsp90 inhibitors may represent a new class of antiviral compounds against influenza viruses...
  48. ncbi The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin
    T W Schulte
    Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1928, USA
    Cancer Chemother Pharmacol 42:273-9. 1998
    ..We therefore examined the biologic effects of 17-allylamino-17-demethoxygeldanamycin (17-AG), an ansamycin derivative with lower in vivo toxicity than GA...
  49. ncbi Inhibition of heat shock protein 90 impairs epidermal growth factor-mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivo
    Sven A Lang
    Departments of Surgery and Surgical Oncology, University of Regensburg, Franz Josef Strauss Allee 11, 93042 Regensburg, Germany
    Mol Cancer Ther 6:1123-32. 2007
    ..Hence, gastric cancer harbors attractive molecular targets for therapy with Hsp90 inhibitors, which could lead to improved efficacy of antineoplastic therapy regimens...
  50. ncbi Regulation of tumor cell mitochondrial homeostasis by an organelle-specific Hsp90 chaperone network
    Byoung Heon Kang
    Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    Cell 131:257-70. 2007
    ..Therefore, Hsp90-directed chaperones are regulators of mitochondrial integrity, and their organelle-specific antagonists may provide a previously undescribed class of potent anticancer agents...
  51. ncbi Therapeutic and diagnostic implications of Hsp90 activation
    Adeela Kamal
    Department of Biology, Conforma Therapeutics Corporation, 9393 Towne Centre Drive, Suite 240, San Diego, CA 92121, USA
    Trends Mol Med 10:283-90. 2004
    ..This review discusses these recent advances in the understanding of tumor Hsp90 for the treatment and diagnosis of cancer. In addition, the role of Hsp90 in non-oncological diseases will also be discussed...
  52. pmc Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration
    Gang Ming Zou
    Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB 2, M341, Baltimore, MD 21231, USA
    Mol Cancer Ther 7:2012-21. 2008
    ..Inhibition of the APE1 redox function through pharmacologic means has the potential to become a promising therapeutic strategy in this disease...
  53. ncbi The heat-shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin suppresses glial inflammatory responses and ameliorates experimental autoimmune encephalomyelitis
    Cinzia Dello Russo
    Department of Anesthesiology, University of Illinois, and Jesse Brown Veteran s Affairs Research Division, Chicago, Illinois 60612, USA
    J Neurochem 99:1351-62. 2006
    ..Together, these data suggest that HSP90 inhibitors could represent a new approach for therapeutic intervention in autoimmune diseases such as multiple sclerosis...
  54. ncbi Thymoquinone induces apoptosis through activation of caspase-8 and mitochondrial events in p53-null myeloblastic leukemia HL-60 cells
    Mohamed A El-Mahdy
    Department of Radiology, Ohio State University, Columbus, OH 43210, USA
    Int J Cancer 117:409-17. 2005
    ..Activated caspase-8 initiates the release of cytochrome c during TQ-induced apoptosis. Overall, these results offer a potential mechanism for TQ-induced apoptosis in p53-null HL-60 cancer cells...
  55. pmc Role of the multifunctional DNA repair and redox signaling protein Ape1/Ref-1 in cancer and endothelial cells: small-molecule inhibition of the redox function of Ape1
    Meihua Luo
    Department of Pediatrics Section of Hematology Oncology, Herman B Wells Center for Pediatric Research, Indianapolis, Indiana 46202, USA
    Antioxid Redox Signal 10:1853-67. 2008
    ..Here we discuss small-molecule inhibition of Ape1 redox and its effect on both cancer and endothelial cells...
  56. ncbi Embelin induces apoptosis through down-regulation of XIAP in human leukemia cells
    Rong Hu
    Department of Hematology, Shengjing Hospital, China Medical University, 110004, Shenyang, China
    Med Oncol 28:1584-8. 2011
    ..Taken together, these findings suggest that embelin results in human leukemia cells apoptosis through caspase-dependent mechanisms involving down-regulation of XIAP...
  57. ncbi Apoptosis caused by Hsp90 inhibitor geldanamycin in Leishmania donovani during promastigote-to-amastigote transformation stage
    Qiaoli Li
    Bio X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of Education, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China
    Parasitol Res 105:1539-48. 2009
    ..donovani but could not cause stage differentiation in high temperature and that acidic conditions were likely to be crucial for the transformation and survival of the parasite within its human host...
  58. pmc Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90
    Toru Okamoto
    Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
    EMBO J 25:5015-25. 2006
    ..These results suggest that the complex consisting of NS5A, FKBP8, and Hsp90 plays an important role in HCV RNA replication...
  59. ncbi Geldanamycin induces heat shock protein 70 and protects against MPTP-induced dopaminergic neurotoxicity in mice
    Hai Ying Shen
    Molecular Neuropharmacology Laboratory, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 280:39962-9. 2005
    ....
  60. ncbi Abrogation of heat shock protein 70 induction as a strategy to increase antileukemia activity of heat shock protein 90 inhibitor 17-allylamino-demethoxy geldanamycin
    Fei Guo
    Department of Interdisciplinary Oncology, H Lee Moffitt Cancer Center, Tampa, Florida 33612, USA
    Cancer Res 65:10536-44. 2005
    ..Collectively, these data indicate that induction of hsp70 attenuates the apoptotic effects of 17-AAG, and abrogation of hsp70 induction significantly enhances the antileukemia activity of 17-AAG...
  61. ncbi Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer
    Sanjeev Banerjee
    Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA
    Cancer Res 69:5575-83. 2009
    ....
  62. pmc Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways
    Tingfang Yi
    Center for Cancer and Stem Cell Biology, Institute for Bioscience and Technology, Texas A and M University System Health Science Center, 2121 West Holcombe Boulevard, Houston, TX 77030, USA
    Mol Cancer Ther 7:1789-96. 2008
    ..Overall, our results indicate that thymoquinone inhibits tumor angiogenesis and tumor growth and could be used as a potential drug candidate for cancer therapy...
  63. pdf Thymoquinone reduces mouse colon tumor cell invasion and inhibits tumor growth in murine colon cancer models
    Hala Gali-Muhtasib
    Department of Biology, American University of Beirut, Beirut, Lebanon
    J Cell Mol Med 12:330-42. 2008
    ..These data should encourage further in vivo testing and support the potential use of TQ as a therapeutic agent in human colorectal cancer...
  64. ncbi A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors
    Adeela Kamal
    Conforma Therapeutics Corporation, 9393 Towne Centre Drive, Suite 240, San Diego, California 92121, USA
    Nature 425:407-10. 2003
    ..These results suggest that tumour cells contain Hsp90 complexes in an activated, high-affinity conformation that facilitates malignant progression, and that may represent a unique target for cancer therapeutics...
  65. pmc The molecular chaperone Hsp90 plays a role in the assembly and maintenance of the 26S proteasome
    Jun Imai
    Department of Molecular Oncology and Department of Cell Biology, Tokyo Metropolitan Institute of Medical Science, Honkomagome 3 18 22, Bunkyo ku, Tokyo 113 8613, CREST, Japan
    EMBO J 22:3557-67. 2003
    ..Our results indicate that Hsp90 interacts with the 26S proteasome and plays a principal role in the assembly and maintenance of the 26S proteasome...
  66. pmc Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome
    M A Loo
    Mayo Foundation, S C Johnson Medical Research Center, Mayo Clinic Scottsdale, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA
    EMBO J 17:6879-87. 1998
    ..This is the first direct evidence of a role for Hsp90 in the maturation of a newly synthesized integral membrane protein by interaction with its cytoplasmic domains on the ER surface...
  67. ncbi Identification of heat-shock protein 90 beta in Japanese encephalitis virus-induced secretion proteins
    Chun Yu Hung
    Department of Biomedical Sciences, Chang Gung University, Tao Yuan 33302, Taiwan, ROC
    J Gen Virol 92:2803-9. 2011
    ..Our results show that Hsp90β, not Hsp90α, is present in the JEV-induced secretion medium and is required for JEV infectivity in BHK-21 cells...
  68. pmc Hsp90 inhibitor 17-AAG inhibits progression of LuCaP35 xenograft prostate tumors to castration resistance
    Katherine J O'malley
    Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA
    Prostate 72:1117-23. 2012
    ..This study addresses whether targeting Heat shock protein 90 (HSP90) regulation of androgen receptor (AR) can inhibit prostate cancer progression to castration resistance...
  69. pmc Multicenter phase II trial of the heat shock protein 90 inhibitor, retaspimycin hydrochloride (IPI-504), in patients with castration-resistant prostate cancer
    William K Oh
    Mount Sinai School of Medicine, New York, New York 10029, USA
    Urology 78:626-30. 2011
    ..To evaluate clinical activity and safety of retaspimycin hydrochloride (IPI-504) in patients with castration-resistant prostate cancer (CRPC)...
  70. ncbi Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (NSC 707545) in CD2F1 mice and Fischer 344 rats
    Merrill J Egorin
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, PA 15213, USA
    Cancer Chemother Pharmacol 49:7-19. 2002
    ..p. and oral delivery; (3) characterize the biliary excretion of 17DMAG after i.v. delivery to rats; and (4) characterize, if possible, any metabolites of 17DMAG observed in plasma, tissue, urine, or bile...
  71. ncbi The heat shock protein 90 of Leishmania donovani
    M Wiesgigl
    Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
    Med Microbiol Immunol 190:27-31. 2001
    ..We propose a role for Hsp90 in the feedback control of the cellular stress response and in the control of the parasite's life cycle...
  72. ncbi Thymoquinone inhibits growth and augments 5-fluorouracil-induced apoptosis in gastric cancer cells both in vitro and in vivo
    Xiaofei Lei
    Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, PR China
    Biochem Biophys Res Commun 417:864-8. 2012
    ....
  73. pmc Heat shock protein 90 homeostasis controls stage differentiation in Leishmania donovani
    M Wiesgigl
    Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany
    Mol Biol Cell 12:3307-16. 2001
    ..Our results are consistent with Hsp90 homeostasis serving as cellular thermometer for these primitive eukaryotes, controlling both the heat shock response and morphological differentiation...
  74. ncbi Anti-malarial, anti-trypanosomal, and anti-leishmanial activities of jacaranone isolated from Pentacalia desiderabilis (Vell.) Cuatrec. (Asteraceae)
    Thiago R Morais
    Centro de Ciências e Humanidades e Centro de Ciências Biológias e da Saúde, Universidade Presbiteriana Mackenzie, 01302 907, Sao Paulo, SP, Brazil
    Parasitol Res 110:95-101. 2012
    ..75 μg/mL) and a selectivity index of 3. The obtained results suggested that jacaranone, as other similar secondary metabolites or synthetic analogs, might be useful tolls for drug design for in vivo studies against protozoan diseases...
  75. pmc Gambogic acid, a natural product inhibitor of Hsp90
    Jason Davenport
    Department of Biochemistry and Molecular Biology, 246 Noble Research Center, Oklahoma State University, Stillwater, Oklahoma 74078, United States
    J Nat Prod 74:1085-92. 2011
    ..The data obtained have firmly established 1 as a novel Hsp90 inhibitor and have provided evidence of a new site that can be targeted for the development of improved Hsp90 inhibitors...
  76. pmc Interactions of apurinic/apyrimidinic endonuclease with a redox inhibitor: evidence for an alternate conformation of the enzyme
    Dian Su
    Department of Chemistry, Washington University in St Louis, St Louis, Missouri 63130, United States
    Biochemistry 50:82-92. 2011
    ..Collectively, our results suggest that APE1 adopts a partially unfolded state, which we propose is the redox active form of the enzyme...
  77. pmc Hsp90 is required for the activity of a hepatitis B virus reverse transcriptase
    J Hu
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    Proc Natl Acad Sci U S A 93:1060-4. 1996
    ..This RNP complex is required early in replication for viral assembly and initiation of DNA synthesis through a protein-priming mechanism. These results thus invoke a role for the Hsp90 pathway in the formation of an RNP...
  78. pmc Hsp90 inhibitors block outgrowth of EBV-infected malignant cells in vitro and in vivo through an EBNA1-dependent mechanism
    Xiaoping Sun
    Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 107:3146-51. 2010
    ..These results suggest that Hsp90 inhibitors may be particularly effective for treating EBV-induced diseases requiring the continued presence of the viral genome...
  79. ncbi TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90
    Guoqing Chen
    Tularik, Incorporated, Two Corporate Drive, South San Francisco, CA 94080, USA
    Mol Cell 9:401-10. 2002
    ..Therefore, heterocomplex formation with Cdc37/Hsp90 is a prerequisite for TNF-induced activation and trafficking of IKK from the cytoplasm to the membrane...
  80. ncbi Hsp90 inhibitors, GA and 17AAG, lead to ER stress-induced apoptosis in rat histiocytoma
    Aftab Taiyab
    Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India
    Biochem Pharmacol 78:142-52. 2009
    ..We conclude that inhibition of Hsp90 leads to ER stress-induced mitochondria-mediated apoptosis and that Bax and Ca(2+) play an important role in mitochondrial damage...
  81. pmc Heat-shock protein 90 is essential for stabilization of the hepatitis C virus nonstructural protein NS3
    Saneyuki Ujino
    Department of Life and Environmental Sciences, High Technology Research Center, Research Institute, Chiba Institute of Technology, 2 17 1 Tsudanuma, Narashino, Chiba 275 0016, Japan
    J Biol Chem 284:6841-6. 2009
    ..These results suggest that the suppression of HCV RNA replication is due to the destabilization of NS3 in disruption of the Hsp90 chaperone complex by 17-AAG...
  82. ncbi Protective effect of Nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells death
    S H Mousavi
    Department of Pharmacology and Pharmacological Research Centre of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences MUMS, Mashhad, Iran
    Cell Mol Neurobiol 30:591-8. 2010
    ..Our findings might raise the possibility of potential therapeutic application of N. sativa extract and TQ for managing cerebral ischemic and neurodegenerative disorders...
  83. ncbi Discovery and development of Hsp90 inhibitors: a promising pathway for cancer therapy
    James R Porter
    Infinity Pharmaceuticals, Inc, 780 Memorial Drive, Cambridge, MA 02139, USA
    Curr Opin Chem Biol 14:412-20. 2010
    ..The most advanced candidates are now in Phase 2 clinical trials and defining the therapeutic window, dosing schedule, and indication are the primary challenges for these potential first-in-class inhibitors...
  84. ncbi Heat-shock protein 90 (Hsp90) as a molecular target for therapy of gastrointestinal cancer
    Christian Moser
    Department of Surgery, University of Regensburg Medical Center, 93042 Regensburg, Germany
    Anticancer Res 29:2031-42. 2009
    ..Against this background, the following review focuses on the current preclinical experience and value of targeting Hsp90 for the therapy of gastrointestinal carcinomas...
  85. pmc Phase I trial of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein inhibitor, administered twice weekly in patients with advanced malignancies
    Shivaani Kummar
    Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
    Eur J Cancer 46:340-7. 2010
    ....
  86. ncbi Inhibitory effects of thymoquinone against 20-methylcholanthrene-induced fibrosarcoma tumorigenesis
    O A Badary
    Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt
    Cancer Detect Prev 25:362-8. 2001
    ..The possible modes of action of TQ may be through its antioxidant activity and interference with the DNA synthesis coupled with enhancement of detoxification processes...
  87. pmc Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway
    Feng Li
    Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
    Br J Pharmacol 161:541-54. 2010
    ..In the present report, we investigated whether thymoquinone (TQ), the main component isolated from the medicinal plant Nigella sativa, modulated the STAT3 signalling pathway in MM cells...
  88. ncbi CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation
    Leonard Petrucelli
    Mayo Clinic, Jacksonville, FL 32224, USA
    Hum Mol Genet 13:703-14. 2004
    ..Hsp70/CHIP may therefore play an important role in the pathogenesis of tauopathies and also represents a potential therapeutic target...
  89. ncbi Binding of p23 and hsp90 during assembly with the progesterone receptor
    J L Johnson
    Department of Biochemistry and Molecular Biology, Mayo Graduate School, Rochester, Minnesota 55905, USA
    Mol Endocrinol 9:670-8. 1995
    ..A model is presented to relate these findings to previous models and another complex between hsp90, hsp70, and p60 that appears to be an intermediate in PR assembly...
  90. pmc A proteomic investigation of ligand-dependent HSP90 complexes reveals CHORDC1 as a novel ADP-dependent HSP90-interacting protein
    Jacob J Gano
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Mol Cell Proteomics 9:255-70. 2010
    ..Together these findings suggest that the HSP90 interactome is dynamic with respect to nucleotide and drug ligands and that pharmacological inhibition of HSP90 may stimulate the formation of specific complexes...
  91. ncbi Up-regulation of heat shock protein 27 induces resistance to 17-allylamino-demethoxygeldanamycin through a glutathione-mediated mechanism
    Andrea K McCollum
    Department of Molecular Pharmacology, Mayo Clinic College of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA
    Cancer Res 66:10967-75. 2006
    ..Our results suggest that Hsp27 up-regulation has a significant role in 17-AAG resistance, which may be mediated in part through GSH regulation. Clinical modulation of GSH may therefore enhance the efficacy of Hsp90-directed therapy...
  92. ncbi FLT3 expressing leukemias are selectively sensitive to inhibitors of the molecular chaperone heat shock protein 90 through destabilization of signal transduction-associated kinases
    Qing Yao
    University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, USA
    Clin Cancer Res 9:4483-93. 2003
    ..We conducted studies to evaluate the hypothesis that FLT3 is a client of heat shock protein (Hsp) 90 and inhibitors of Hsp90 may be useful for therapy of leukemia...
  93. ncbi Plasmodial heat shock proteins: targets for chemotherapy
    Addmore Shonhai
    Department of Biochemistry and Microbiology, Zululand University, KwaDlangezwa, South Africa
    FEMS Immunol Med Microbiol 58:61-74. 2010
    ..The proposed mechanisms of action of these molecules and the pathways they inhibit are discussed...
  94. ncbi Effects of small molecules on chaperone-mediated autophagy
    Patrick F Finn
    Department of Cellular and Molecular Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    Autophagy 1:141-5. 2005
    ..Finally we demonstrate that the glucose-6-phophate dehydrogenase inhibitor, 6-aminonicotinamide, and heat shock protein of 90 kilodaltons inhibitor, geldanamycin, have the ability to activate CMA...
  95. ncbi Thymoquinone is a potent superoxide anion scavenger
    Osama A Badary
    Department of Pharmacology and Toxicology, College of Pharmacy, Al Azhar University, Nasr City, Cairo, Egypt
    Drug Chem Toxicol 26:87-98. 2003
    ..The results suggest that both TQ and TBHQ have strong antioxidant potentials through scavenging ability of different free radicals. Moreover, the data indicate that TQ is acting mainly as a potent superoxide anion scavenger...
  96. ncbi 17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in an SBMA model mouse
    Keisuke Tokui
    Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai Cho, Showa Ku, Nagoya 466 8550, Japan
    Hum Mol Genet 18:898-910. 2009
    ..17-DMAG also significantly induced Hsp70 and Hsp40. Thus, 17-DMAG would exert a therapeutic effect on SBMA via preserved proteasome function...
  97. ncbi Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease
    A Sittler
    , Ihnestrasse 73, D-14195 Berlin, Germany
    Hum Mol Genet 10:1307-15. 2001
    ..These findings may provide the basis for the development of a novel pharmacotherapy for HD and related glutamine repeat disorders...
  98. pmc COMMD1 Promotes pVHL and O2-Independent Proteolysis of HIF-1alpha via HSP90/70
    Bart van De Sluis
    Complex Genetics Section, DBG Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
    PLoS ONE 4:e7332. 2009
    ..Although HIF activity is mainly controlled by ubiquitination and protein degradation by the von Hippel Lindau (pVHL) tumor suppressor gene other mechanisms have recently been identified that regulate HIF signaling independently of pVHL...
  99. ncbi Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells
    Nicola J Mabjeesh
    Winship Cancer Institute, Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Cancer Res 62:2478-82. 2002
    ..Thus, benzoquinone ansamycin drugs and their derivatives, such as 17-allyl-aminogeldanamycin, are excellent candidates as small molecule drug inhibitors of HIF-1 overexpression in cancer cells...
  100. pmc Rapid glucocorticoid receptor exchange at a promoter is coupled to transcription and regulated by chaperones and proteasomes
    Diana A Stavreva
    Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute Light Imaging Facility, National Institute for Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA
    Mol Cell Biol 24:2682-97. 2004
    ..Moreover, our results reveal that longer GR residence times are consistently associated with greater transcriptional output, suggesting a new paradigm in which the rate of rapid exchange provides a means to tune transcriptional levels...
  101. ncbi 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells
    Gerard Fumo
    National Cancer Institute, Cell and Cancer Biology Branch, 9610 Medical Center Dr, Ste 300, Rockville, MD 20850, USA
    Blood 103:1078-84. 2004
    ..These data provide compelling evidence that 17-AAG may be effective in the treatment of c-kit-related diseases including mastocytosis, GISTs, mast cell leukemia, subtypes of acute myelogenous leukemia, and testicular cancer...

Research Grants67

  1. Novel Mechanisms of Quinone Toxicity
    David Ross; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Both benzoquinones and naphthoquinones have been found to perturb protein handling and degradation in a variety of cellular systems...
  2. Arthropod-Based Libraries for High Throughput Screening
    Frank Schroeder; Fiscal Year: 2009
    ..characterized have simple structures (such as straight chain alkenes, carboxylic acids, aldehydes, phenols, benzoquinones), there are also many examples of biologically active alkaloids, isoprenoids (including steroids), and ..
  3. SYNTHESIS OF BIOLOGICALLY IMPORTANT DIHYDROBENZOFURANS
    Thomas Engler; Fiscal Year: 1991
    A study is proposed of the Lewis acid catalyzed reactions of various alkenes and cyclopropanes with methoxy-1,4-benzoquinones to selectively yield dihydrobenzofurans A-C and chromans D-F, respectively...
  4. SECRETIONS OF ARTHROPODS
    Thomas Eisner; Fiscal Year: 2008
    ..Insects are major vectors of disease. An understanding of how insects depend on natural products for regulation of their biotic interactions is of broad applied significance to both medicine and agriculture. [unreadable] [unreadable]..
  5. PROTON & ELECTRON TRANSFER & ENERGY COUPLING IN SITE I
    TOMOKO NONE OHNISHI; Fiscal Year: 2010
    ..Using this new strategy, we found that both cluster N2 and flavin can generate superoxide. We will solidify this exciting finding and study its relevance to complex I function under physiological and pathological conditions. ..
  6. FP Assay for Isolation of Hsp90 Inhibitors (RMI)
    Gabriela Chiosis; Fiscal Year: 2005
    ....
  7. 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. ..
  8. Assays for rapid identification of Hsp70 modulators
    Gabriela Chiosis; Fiscal Year: 2008
    ..abstract_text> ..
  9. Hsp90 inhibitors as suppressors of protein misfolding toxicity
    Gabriela Chiosis; Fiscal Year: 2008
    ..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. [unreadable] [unreadable] [unreadable]..
  10. Regulation of Lung Epithelial Fibrinolysis by Urokinase
    Sreerama Shetty; Fiscal Year: 2005
    ..This information could hasten the development of new, mechanism-based interventions for lung disorders, including acute lung injury or lung neoplasia. ..
  11. 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. ..
  12. CONTROL OF FIBRINOLYTIC PATHWAYS IN LUNG DISEASE
    Sreerama Shetty; Fiscal Year: 2004
    ..abstract_text> ..
  13. Arsenic Trioxide Down-Regulates STAT3 Activity in AML
    Meir Wetzler; Fiscal Year: 2004
    ..In addition, we will attempt to identify the mode by which ATO controls the activity of STAT3 and how this effect alters the gene profile patterns and induces apoptosis. ..
  14. 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]..
  15. Defibrotide for the treatment of severe hepatic veno-cc*
    Paul Richardson; Fiscal Year: 2007
    ..Abstract Not Provided ..
  16. REDOX ACTIVITY OF THE PULMONARY ENDOTHELIAL SURFACE
    MARILYN MERKER; Fiscal Year: 2008
    ....
  17. Chemosensitization of Pancreatic Tumors via Inhibition of a DNA BER Enzyme, Ape1
    Melissa Fishel; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  18. Modulation of K channels in renal collecting duct
    Wen Hui Wang; Fiscal Year: 2007
    ....
  19. SYNTHESIS OF MDR REVERSING POLYENES
    MERRITT ANDRUS; Fiscal Year: 2003
    ..This is an important first step toward a molecular understanding of the unique recognition properties, transport mechanism of Pgp, and will further facilitate the design of new, more potent reversal agents. ..
  20. Reduction of Alkylating Quinones and Nitroarenes
    ANTONIO ALEGRIA; Fiscal Year: 2003
    ..Undergraduate students will participate in this project, thus improving their qualifications to pursue biomedical research careers. ..
  21. Potentiation of Topo Inhibitors by HDAC Inhibitors
    Pamela Munster; Fiscal Year: 2005
    ..Finally, the utility of the topo II inhibitors could be enhanced if their efficacy could be increased without worsening toxicity, as our preclinical data appears to indicate. ..
  22. Role of Calcineurin in Fungal Virulence
    Joseph Heitman; Fiscal Year: 2009
    ..Importantly, this pathway can be targeted for therapeutic intervention using non-immunosuppressive calcineurin inhibitors that retain antifungal activity and synergistic drug combinations that we have discovered. ..
  23. Salt Absorption by the THAL: Role of NKCC2 trafficking
    Pablo A Ortiz; Fiscal Year: 2010
    ..Data from this proposal will increase our understanding of how salt absorption by the THAL is regulated in normal and salt-sensitive animals, and will identify new targets for the development of diuretics. ..
  24. Annual Midwest DNA Repair Symposium
    Altaf Wani; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  25. Enhancing Photodynamic Therapy for Treating Kaposi's Sarcoma
    Charles Gomer; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  26. Hsp90 Chaperone Machine Structure and Function
    Avrom Caplan; Fiscal Year: 2009
    ..In the second sub-aim we will assay for chaperone activity of novel co-chaperones that are important for protein kinase folding. Finally, we will distinguish between the role of Cdc37 in Cdk folding and cyclin binding. ..
  27. Lipid Raft Microdomains in Neutrophil Function
    ROBERT GARY SITRIN; Fiscal Year: 2010
    ..Hopefully, targeting the function of lipid raft microdomains will engender new therapeutic strategies for enhancing antimicrobial defenses and suppressing the deleterious effects of acute inflammation. ..
  28. GPCR signaling cascades in Cryptococcus neoformans
    Joseph Heitman; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  29. Invasion and Angiogenesis in Malignant Gliomas
    David Zagzag; Fiscal Year: 2008
    ..Results from these experiments will lead to future strategies designed to inhibit specific molecular components implicated in these critical processes. ..
  30. Hsp90/Client Protein Interactions in the Newborn Lung
    Judy Aschner; Fiscal Year: 2008
    ..These studies will improve understanding of the neonatal pulmonary hypertensive response to chronic hypoxia and are critical to the formulation of novel treatment strategies for infants with PH. ..
  31. A Metabolomic Approach to Discovering Biomarkers for ADPKD
    Robert H Weiss; Fiscal Year: 2010
    ..In addition, work from this proposal will lead to new knowledge about the pathology of the disease and to selection of patients who will most benefit from any new drug. ..
  32. Aging and brain 5-lipoxygenase
    Hari Manev; Fiscal Year: 2010
    ..The proposed experiments may corroborate the hypothesis that epigenetic mechanisms are involved in brain aging. ..
  33. Synthesis of Macrolides, Steroids, Cyclopentanoids, etc.
    BARRY TROST; Fiscal Year: 2009
    ..These new synthetic methods apply to many structural types beyond those illustrated and constitutes a significant to gain access to complex molecular targets more easily. ..
  34. Genetics of mating and fruiting in Cryptococcus neoformans
    Joseph Heitman; Fiscal Year: 2010
    ..neoformans and C. gattii applicable to development of treatment approaches, diagnostics, or environmental interventions to reduce exposure to infectious spores. ..
  35. TGF-BETAS AND RECEPTORS AND HUMAN BREAST CELLS
    Carlos Arteaga; Fiscal Year: 2009
    ..Specific Aim 4: To determine if the activated type I TGFbeta receptor (Alk5) synergizes with HER2 (erbB2) in mammary tumorigenesis and whether it negates the therapeutic effect of HER2 inhibitors in vivo. ..
  36. SCREENS TO IDENTIFY GAIN OF FUNCTION AH RECEPTOR MUTANTS INVOLVED IN DEGRADATION
    RICHARD POLLENZ; Fiscal Year: 2008
    ..e. steroid hormone receptors). [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  37. Hsp90, NOS3 and Cardioprotection
    Yang Shi; Fiscal Year: 2009
    ..abstract_text> ..
  38. Airway muscle tone, RhoA & Cytoskeletal remodeling
    CAROL HIRSHMAN; Fiscal Year: 2007
    ....
  39. Brain Manganese Deposition in High Risk Neonates
    Judy Aschner; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  40. Enhancing Photodynamic Therapy with COX-2 Inhibition
    Charles Gomer; Fiscal Year: 2007
    ..If our preliminary findings are confirmed by studies outlined in this proposal, adjunctive COX-2 inhibitor treatment could provide a safe and effective method for improving clinical PDT. [unreadable] [unreadable]..
  41. Is Tissue ACE Required for Diabetic Renal Damage?
    Harold Franch; Fiscal Year: 2005
    ..We believe that this approach will not only critically test our hypothesis, but will also lay the ground work for future studies into the role of ACE in the diabetic kidney. ..
  42. MULTIDISCIPLINARY TRAINING IN EXPERIMENTAL HEMATOLOGY
    Scott Kaufmann; Fiscal Year: 2005
    ..This program is a natural outgrowth of existing training opportunities in hematology, but will provide better preparation for laboratory research in hematological diseases. (End of Abstract) ..
  43. OXIDATIVE DNA DAMAGE AND REPAIR IN CNS CELLS
    Mark Kelley; Fiscal Year: 2003
    ..abstract_text> ..
  44. LARG, A Novel Leukemia Associated Guanine Exhange Factor
    Guido Marcucci; Fiscal Year: 2006
    ..i.). ..
  45. Proposed Role for Neuronal Serotonin N-acetyltransferase
    Hari Manev; Fiscal Year: 2006
    ..We expect the results to elucidate the role of AANAT/NAS in neuronal functioning, and in the long term, in the pathobiology of depression. ..
  46. BCI2 Antisense Against Chemoresistance in Elderly AML
    Guido Marcucci; Fiscal Year: 2003
    ..It is expected that the analysis of the clinical and correlative laboratory results will support testing of this combination in a phase III setting. ..
  47. Structural Basis for Isoprenoid Biosynthesis
    JOSEPH NOEL; Fiscal Year: 2006
    ....
  48. TERPENE CYCLASES: FUNCTIONAL DOMAINS AND STRUCTURES
    JOSEPH NOEL; Fiscal Year: 2003
    ..Our current objective is to understand the regiochemical and stereochemical principles that govern the biosynthesis of pharmaceutically useful terpenoids. ..
  49. Pharmacologic modulation of chromatin remodeling in leu*
    Guido Marcucci; Fiscal Year: 2006
    ..Further, we believe that this schedule is amenable to future combination-based approaches. [unreadable] [unreadable]..
  50. Control of elF4F complex by Vesicular Stomatitis Virus
    John Connor; Fiscal Year: 2007
    ....
  51. Preclinical Evaluation of Bcr/Abl-Directed Tyrphostins
    Scott Kaufmann; Fiscal Year: 2007
    ..abstract_text> ..
  52. The Urokinase-CD87 System in Macrophage Activation
    Robert Sitrin; Fiscal Year: 2004
    ....
  53. Does FAK mediate implant microtopography
    Galen Schneider; Fiscal Year: 2006
    ..This would allow for a controlled, localized, site specific tissue engineering approach in association with Dental implant therapy. ..
  54. Molecular Neurobiology of Drug Abuse
    DONALD KUHN; Fiscal Year: 2006
    ..Kuhn will remain extensively engaged in scientific mentoring activities. ..
  55. Alzheimer's Disease Research Center Conference
    Leon Thal; Fiscal Year: 2006
    ..Partial support is requested to defray travel costs of invited speakers and to provide travel awards to minority healthcare providers, junior faculty, postdocs and students. [unreadable] [unreadable] [unreadable]..
  56. PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDER
    DONALD KUHN; Fiscal Year: 2002
    ....
  57. Biochemical Effects of Disrupting HSP90
    Charles Erlichman; Fiscal Year: 2004
    ....
  58. FLOW SHEAR INDUCED NF-KB MEDIATED REGULATION
    Sumathy Mohan; Fiscal Year: 2003
    ..Understanding of NF- kappaB signaling mechanisms in VCAM-1 regulation can also be applied to other inflammatory conditions. ..
  59. Acquisition of FACSVantage SE Flow Cytometer
    Yair Gazitt; Fiscal Year: 2004
    ..The new equipment will also widen the user's base, save sort time, reduce costs for users and will render sorting affordable to new users, especially in cases where low frequency (<1%) cell populations are sorted. ..
  60. SYNTHESIS OF THE TEDANOLIDES, CYTOTOXIC POLYPROPIONATES
    Michael Jung; Fiscal Year: 2003
    ....
  61. Prostanoids and hypoxic neonatal pulmonary hypertension
    CANDICE FIKE; Fiscal Year: 2009
    ..The goal of this project is to help us understand why infants develop pulmonary hypertension, determine what happens in the lung blood vessels during disease development, and develop treatments for this disease. ..
  62. NOVEL THERAPIES FOR ACETAMINOPHEN TOXICITY
    Laura James; Fiscal Year: 2004
    ..abstract_text> ..
  63. Evaluation of a Biomarker for Acetaminophen Toxicity
    Laura James; Fiscal Year: 2005
    ..The data generated from this study will lead to enhanced recognition of APAP hepatotoxicity, thus allowing for better identification of "at risk" populations and the creation of prevention strategies. ..
  64. Regulation of exocrine cell secretion by Rab proteins
    Robert Raffaniello; Fiscal Year: 2006
    ..Therefore, an understanding of the basic mechanisms that regulate exocrine gland secretion is essential. [unreadable] [unreadable]..
  65. Engineering Large scale pathways from organisms to Escherichia coli
    James Liao; Fiscal Year: 2008
    ..In particular, selected projects proposed here will be used as modules in a workshop established by FRT at Ohio State and form the basis for a course (Metabolic Engineering) at UCLA. ..
  66. Chemogenomic Analysis of E. coli Response to NO species
    James C Liao; Fiscal Year: 2010
    ..If hew TF targets are predicted, then the iteration continues. Otherwise, the predicted networks are verified using genetic and biochemical experiments. ..
  67. Automated Chip-Based Metabolomic Analysis
    James Liao; Fiscal Year: 2006
    ..abstract_text> ..