macrocyclic lactams

Summary

Summary: LACTAMS forming compounds with a ring size of approximately 1-3 dozen atoms.

Top Publications

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

Research Grants

Detail Information

Publications233 found, 100 shown here

  1. 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...
  2. 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
    ....
  3. 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...
  4. 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
    ....
  5. 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...
  6. 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...
  7. 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...
  8. 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...
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. pmc Hsp90 regulates the function of argonaute 2 and its recruitment to stress granules and P-bodies
    Justin M Pare
    Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
    Mol Biol Cell 20:3273-84. 2009
    ..Together, our data suggest that Hsp90 is a critical modulator of Argonaute function. Moreover, we propose that Ago2 and PACT form a complex that functions at the level of SGs...
  14. ncbi Phase I and pharmacologic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with solid tumors
    Jean L Grem
    Nebraska Medical Center, Omaha, NE 68198 7680, USA
    J Clin Oncol 23:1885-93. 2005
    ..To determine the clinical toxicities of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) given as a 1-hour infusion daily for 5 days every 3 weeks...
  15. 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...
  16. pmc Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin
    T W Schulte
    Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Cell Stress Chaperones 3:100-8. 1998
    ..Radicicol thus represents a structurally unique antibiotic, and the first non-benzoquinone ansamycin, capable of binding to Hsp90 and interfering with its function...
  17. 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...
  18. ncbi Molecular chaperones and protein kinase quality control
    Avrom J Caplan
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA
    Trends Cell Biol 17:87-92. 2007
    ..This requirement might relate to conformational changes that take place during the protein kinase activity cycle...
  19. ncbi Differential effects of the hsp70-binding protein BAG-1 on glucocorticoid receptor folding by the hsp90-based chaperone machinery
    K C Kanelakis
    Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 274:34134-40. 1999
    ....
  20. 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...
  21. 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...
  22. ncbi Geldanamycin-induced destabilization of Raf-1 involves the proteasome
    T W Schulte
    Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA
    Biochem Biophys Res Commun 239:655-9. 1997
    ..Signaling through this pathway was inhibited by GA, concomitant with loss of Raf-1 protein, but was restored if Raf-1 was protected from GA-induced degradation by proteasome inhibitors...
  23. pmc Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway
    T W Schulte
    Clinical Pharmacology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA
    Mol Cell Biol 16:5839-45. 1996
    ..Thus, we demonstrate that interaction between HSP90 and Raf-1 is a sine qua non for Raf stability and function as a signal transducer and that the effects observed cannot be attributed to a general impairment of protein kinase function...
  24. ncbi Geldanamycin induces Hsp70 and prevents alpha-synuclein aggregation and toxicity in vitro
    Pamela J McLean
    Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
    Biochem Biophys Res Commun 321:665-9. 2004
    ....
  25. ncbi Enhanced cell killing induced by the combination of radiation and the heat shock protein 90 inhibitor 17-allylamino-17- demethoxygeldanamycin: a multitarget approach to radiosensitization
    Jeffery S Russell
    Molecular Radiation Therapeutics Branch, Radiation Oncology Science Program, National Cancer Institute, Bethesda, Maryland 20892, USA
    Clin Cancer Res 9:3749-55. 2003
    ..Therefore, in an attempt to increase the probability and/or degree of radiosensitization, we have begun to investigate a multitarget approach using the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17AAG)...
  26. ncbi Inhibition of homologous recombination repair in irradiated tumor cells pretreated with Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin
    Miho Noguchi
    Graduate School of Science and Technology, Chiba University, Inage Ku, Chiba 263 8522, Japan
    Biochem Biophys Res Commun 351:658-63. 2006
    ..Our data demonstrate for the first time that 17-AAG inhibits the HR repair process and could provide a new therapeutic strategy to selectively result in higher tumor cell killing...
  27. 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...
  28. 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
    ....
  29. ncbi Enhanced tumor cell radiosensitivity and abrogation of G2 and S phase arrest by the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin
    Elizabeth E A Bull
    Molecular Radiation Therapeutics Branch, Radiation Oncology Branch, Developmental Therapeutics Program, National Cancer Institute, Bethesda, Maryland, USA
    Clin Cancer Res 10:8077-84. 2004
    ..Therefore, we have investigated the effects of the orally bioavailable Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) on the radiosensitivity of human tumor cells in vitro and grown as tumor xenografts...
  30. ncbi Combinatorial attack on multistep oncogenesis by inhibiting the Hsp90 molecular chaperone
    Paul Workman
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, UK
    Cancer Lett 206:149-57. 2004
    ..This article reviews the current status and future prospects for the exploitation of Hsp90 as a new molecular target for cancer treatment...
  31. 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...
  32. ncbi Pharmacokinetics and pharmacodynamics of 17-demethoxy 17-[[(2-dimethylamino)ethyl]amino]geldanamycin (17DMAG, NSC 707545) in C.B-17 SCID mice bearing MDA-MB-231 human breast cancer xenografts
    Julie L Eiseman
    Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Cancer Chemother Pharmacol 55:21-32. 2005
    ..v. delivery to mice; and (2) correlated tumor and normal tissue 17DMAG concentrations with alterations in heat shock protein 90 (HSP90) and selected HSP90-chaperoned proteins...
  33. ncbi Modulation of Hsp90 function by ansamycins sensitizes breast cancer cells to chemotherapy-induced apoptosis in an RB- and schedule-dependent manner. See: E. A. Sausville, Combining cytotoxics and 17-allylamino, 17-demethoxygeldanamycin: sequence and tumor
    P N Munster
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Clin Cancer Res 7:2228-36. 2001
    ..These findings suggest that inhibition of Hsp90 function by 17-AAG enhances the apoptotic effects of cytotoxic agents. The sequence of drug administration and the RB status significantly influence efficacy...
  34. 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...
  35. ncbi Geldanamycin, an inhibitor of Hsp90, sensitizes human tumour cells to radiation
    H Machida
    Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ami Machi, Ibaraki 300 0394, Japan
    Int J Radiat Biol 79:973-80. 2003
    ..The effects of the heat shock protein 90 (Hsp90) inhibitor geldanamycin (GA) were examined on the radiosensitivity and signal transduction pathways in human tumour cell lines...
  36. ncbi Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), in rats and dogs: potential clinical relevance
    Elizabeth R Glaze
    Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Executive Plaza North, Room 8040, Rockville, MD 20852, USA
    Cancer Chemother Pharmacol 56:637-47. 2005
    ..In addition, 17-DMAG undergoes only limited metabolism compared to 17-AAG. The present results are from preclinical toxicity studies evaluating 17-DMAG in rats and dogs...
  37. pmc Hsp-90 and the biology of nematodes
    Nik A I I N Him
    Parasitology Group, Institute of Comparative Medicine, School of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, UK
    BMC Evol Biol 9:254. 2009
    ..We combined these data with codon evolution models in an attempt to identify whether hsp-90 from GA-binding and non-binding species has evolved under different evolutionary constraints...
  38. ncbi Proteome-wide changes induced by the Hsp90 inhibitor, geldanamycin in anaplastic large cell lymphoma cells
    Jonathan A Schumacher
    Associated and Regional University Pathologists ARUP, Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA
    Proteomics 7:2603-16. 2007
    ..Our studies reveal some of the molecular and proteomic consequences of Hsp90 inhibition in ALK-positive ALCL cells and provide novel insights into the mechanisms of its diverse cellular effects...
  39. ncbi Hsp90 regulates the Fanconi anemia DNA damage response pathway
    Tsukasa Oda
    Laboratory of Molecular Genetics, Department of Molecular and Cellular Biology, Institute of Molecular and Cellular Regulation, Gunma University, 3 39 15 Showa Machi, Maebashi, Gunma 371 8512, Japan
    Blood 109:5016-26. 2007
    ....
  40. ncbi Heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin potentiates the radiation response of tumor cells grown as monolayer cultures and spheroids by inducing apoptosis
    Hikaru Machida
    Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, 4669 2 Ami, Amimachi, Inashiki Gun, Ibaraki 300 0394, Japan
    Cancer Sci 96:911-7. 2005
    ..The findings suggest that 17AAG effectively sensitizes radioresistant cells to radiation by inhibiting the PI3K-Akt pathway. Targeting the PI3K-Akt pathway with 17AAG could be a useful strategy for radiosensitization of carcinomas...
  41. pmc The Hsp90 inhibitor geldanamycin abrogates colocalization of eIF4E and eIF4E-transporter into stress granules and association of eIF4E with eIF4G
    Yukari Suzuki
    Graduate School of Agricultural and Life Sciences, University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 8657, Japan
    J Biol Chem 284:35597-604. 2009
    ....
  42. ncbi Involvement of heat-shock protein 90 in the interleukin-6-mediated signaling pathway through STAT3
    Noriko Sato
    Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita Ku Kita 12 Nishi 6, Sapporo 060 0812, Japan
    Biochem Biophys Res Commun 300:847-52. 2003
    ..We provide evidence that the action of GA on IL-6 functions was due to the inhibition of direct physical interactions between STAT3 and Hsp90, which represents a novel role of Hsp90 in the IL-6 signaling pathways...
  43. ncbi Additive interaction of oxaliplatin and 17-allylamino-17-demethoxygeldanamycin in colon cancer cell lines results from inhibition of nuclear factor kappaB signaling
    Tatiana V Rakitina
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 63:8600-5. 2003
    ..These data support an interaction between 17-AAG and components of the NF-kappaB pathway in the modulation of oxaliplatin sensitivity in colon cancer cells...
  44. ncbi Altered states: selectively drugging the Hsp90 cancer chaperone
    Paul Workman
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, UK
    Trends Mol Med 10:47-51. 2004
    ..However, the reason for therapeutic selectivity in cancer cells versus normal cells is unclear. New research now shows that Hsp90 exists in cancer cells in a heightened, activated state that is highly susceptible to inhibition by 17AAG...
  45. ncbi GERp95 belongs to a family of signal-transducing proteins and requires Hsp90 activity for stability and Golgi localization
    N Tahbaz
    Department of Cell Biology, University of Alberta, Edmonton T6G 2H7, Canada
    J Biol Chem 276:43294-9. 2001
    ..These results indicate that GERp95 engages an Hsp90 chaperone complex prior to association with intracellular membranes...
  46. pmc Genetic and biochemical analysis of p23 and ansamycin antibiotics in the function of Hsp90-dependent signaling proteins
    S P Bohen
    Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    Mol Cell Biol 18:3330-9. 1998
    ..Furthermore, while the presence of p23 decreases the sensitivity of Hsp90-dependent processes to ansamycin treatment, ansamycin antibiotics disrupt signaling through some mechanism other than altering the Hsp90-p23 interaction...
  47. ncbi Small molecule inducers of heat-shock response reduce polyQ-mediated huntingtin aggregation. A possible therapeutic strategy
    Martin Herbst
    Neuroproteomics Group, Max Delbrueck Center for Molecular Medicine, Berlin, Germany
    Neurodegener Dis 4:254-60. 2007
    ..We suggest that geldanamycin derivatives such as 17-DMAG should be considered for the development of a drug treatment for polyQ disorders and other neurodegenerative diseases involving protein aggregation...
  48. ncbi The Hsp90 chaperone complex as a novel target for cancer therapy
    M P Goetz
    Division Medical Oncology, Department of Biochemistry, Mayo Graduate School, Rochester, MN 55905, USA
    Ann Oncol 14:1169-76. 2003
    ..It represents a class of drugs, the benzoquinone ansamycin antibiotics, capable of binding and disrupting the function of Hsp90, leading to the depletion of multiple oncogenic client proteins...
  49. pmc Hsp90 is essential for the synthesis and subsequent membrane association, but not the maintenance, of the Src-kinase p56(lck)
    M J Bijlmakers
    Medical Research Council Laboratory for Molecular Cell Biology and Department of Biochemistry, University College London, London, WC1E 6BT, United Kingdom
    Mol Biol Cell 11:1585-95. 2000
    ..Together these data suggest that interaction with Hsp90 is necessary for the correct synthesis and subsequent membrane binding of Lck. However, Hsp90 does not appear to play a direct role in Lck membrane, or CD4, association...
  50. 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...
  51. ncbi The Hsp90 inhibitor geldanamycin selectively sensitizes Bcr-Abl-expressing leukemia cells to cytotoxic chemotherapy
    M V Blagosklonny
    Department of Developmental Therapeutics, Medicine Branch, National Cancer Institute, NIH, Bethesda and Rockville, MD 20892, USA
    Leukemia 15:1537-43. 2001
    ..Thus, GA differentially affects leukemia cells depending on their Bcr-Abl expression and selectively increases apoptosis in Bcr-Abl-expressing cells...
  52. ncbi Geldanamycin leads to superoxide formation by enzymatic and non-enzymatic redox cycling. Implications for studies of Hsp90 and endothelial cell nitric-oxide synthase
    Sergey Dikalov
    Division of Cardiology, Emory University School of Medicine and Atlanta Veterans Administration Hospital, Georgia 30322, USA
    J Biol Chem 277:25480-5. 2002
    ..In light of these findings, the studies using geldanamycin as an inhibitor of Hsp90 should be interpreted with caution...
  53. ncbi Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer
    Matthew P Goetz
    Division of Medical Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA
    J Clin Oncol 23:1078-87. 2005
    ..We also characterized the pharmacokinetics of 17-AAG, its effect on chaperone and client proteins, and whether cytochrome P450 (CYP) 3A5 and NAD(P)H:quinone oxidoreductase 1 (NQO1) polymorphisms affected 17-AAG disposition or toxicity...
  54. ncbi Hsp90 inhibition depletes Chk1 and sensitizes tumor cells to replication stress
    Sonnet J H Arlander
    Department of Molecular Pharmacology, Mayo Graduate School, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Biol Chem 278:52572-7. 2003
    ..Collectively, our studies identify Chk1 as a novel Hsp90 client and suggest that pharmacologic inhibition of Hsp90 may sensitize tumor cells to chemotherapeutic agents by disrupting Chk1 function during replication stress...
  55. ncbi Combination treatment with 17-N-allylamino-17-demethoxy geldanamycin and acute irradiation produces supra-additive growth suppression in human prostate carcinoma spheroids
    Richard Enmon
    Memorial Sloan Kettering Cancer Center, New York, New York, USA
    Cancer Res 63:8393-9. 2003
    ..These results suggest that significant gains in treatment effectiveness may be obtained by combining these treatment modalities, warranting additional preclinical investigation...
  56. 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...
  57. ncbi Metabolism of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) by murine and human hepatic preparations
    M J Egorin
    Division of Developmental Therapeutics, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore 21201, USA
    Cancer Res 58:2385-96. 1998
    ....
  58. ncbi Geldanamycin, an inhibitor of Hsp90, potentiates cytochrome P4502E1-mediated toxicity in HepG2 cells
    Aparajita Dey
    Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, Box 1603, One Gustave L Levy Place, New York, NY 10029, USA
    J Pharmacol Exp Ther 317:1391-9. 2006
    ..These results suggest that Hsp90 is protective against CYP2E1-dependent oxidant stress and loss of cell viability in HepG2 cells...
  59. pmc HSP90 inhibitor, DMAG, synergizes with radiation of lung cancer cells by interfering with base excision and ATM-mediated DNA repair
    Thuy T Koll
    Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Mol Cancer Ther 7:1985-92. 2008
    ..Thus, administration of HSP90 inhibitors before radiation is critical for optimizing their use as radiosensitizers...
  60. 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...
  61. 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...
  62. ncbi 17-AAG sensitized malignant glioma cells to death-receptor mediated apoptosis
    Markus David Siegelin
    Department of Neuropathology, University Hospital Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany
    Neurobiol Dis 33:243-9. 2009
    ..In addition, over-expression of survivin attenuated cytotoxicity induced by the combination of 17-AAG and TRAIL. In summary, survivin is a key regulator of TRAIL-17-AAG mediated cell death in malignant glioma...
  63. 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...
  64. 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...
  65. ncbi Surface charge and hydrophobicity determine ErbB2 binding to the Hsp90 chaperone complex
    Wanping Xu
    Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Rockville, Maryland 20850, USA
    Nat Struct Mol Biol 12:120-6. 2005
    ..Notably, the immature ErbB2 point mutant remains sensitive to GA, suggesting that mature and nascent client kinases may use distinct motifs to interact with the Hsp90 chaperone complex...
  66. ncbi Progressive decrease in chaperone protein levels in a mouse model of Huntington's disease and induction of stress proteins as a therapeutic approach
    David G Hay
    Medical and Molecular Genetics, GKT School of Medicine, King s College, London, UK
    Hum Mol Genet 13:1389-405. 2004
    ..Radicicol and geldanamycin could both maintain chaperone induction for at least 3 weeks and alter the detergent soluble properties of polyQ aggregates over this time course...
  67. pmc Inhibition of Hsp90 down-regulates mutant epidermal growth factor receptor (EGFR) expression and sensitizes EGFR mutant tumors to paclitaxel
    Ayana Sawai
    Department of Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Cancer Res 68:589-96. 2008
    ....
  68. 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
    ....
  69. ncbi STAT3 and MAPK signaling maintain overexpression of heat shock proteins 90alpha and beta in multiple myeloma cells, which critically contribute to tumor-cell survival
    Manik Chatterjee
    Division of Hematology, University Hospital of Wurzburg, Josef Schneider Strasse 2, 97080 Wurzburg, Germany
    Blood 109:720-8. 2007
    ..Our results underpin a role for Hsp90alpha and beta in MM pathogenesis...
  70. pmc Antimyeloma activity of heat shock protein-90 inhibition
    Constantine S Mitsiades
    Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston MA 02115, USA
    Blood 107:1092-100. 2006
    ....
  71. 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...
  72. ncbi Targeting heat shock protein 90 in pancreatic cancer impairs insulin-like growth factor-I receptor signaling, disrupts an interleukin-6/signal-transducer and activator of transcription 3/hypoxia-inducible factor-1alpha autocrine loop, and reduces orthotop
    Sven A Lang
    Department of Surgery, University of Regensburg Medical Center, Regensburg, Germany
    Clin Cancer Res 13:6459-68. 2007
    ....
  73. 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...
  74. ncbi HSP90 as a new therapeutic target for cancer therapy: the story unfolds
    Alison Maloney
    CRC Centre for Cancer Therapeutics, Institute of Cancer Research, Block E, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
    Expert Opin Biol Ther 2:3-24. 2002
    ..HSP90 inhibitors provide proof of concept for drugs directed at HSP90 and protein folding and this principle may be applicable to other medical conditions involving protein aggregation and stability...
  75. ncbi Stable and specific binding of heat shock protein 90 by geldanamycin disrupts glucocorticoid receptor function in intact cells
    L Whitesell
    Department of Pediatrics, University of Arizona Health Sciences Center, Tucson 85724, USA
    Mol Endocrinol 10:705-12. 1996
    ....
  76. ncbi Pharmacological prevention of Parkinson disease in Drosophila
    Pavan K Auluck
    Nat Med 8:1185-6. 2002
  77. ncbi Clinical development of 17-allylamino, 17-demethoxygeldanamycin
    Edward A Sausville
    Division of Cancer Treatment and Diagnosis, Developmental Therapeutics Program, National Cancer Institute National Cancer Institute, 6130 Executive Blvd, Rm 8018, Rockville, MD 20852, USA
    Curr Cancer Drug Targets 3:377-83. 2003
    ..Evidence of modulation of Hsp90 partner molecules has been obtained in both surrogate and some tumor compartments. These very early results encourage additional clinical evaluations of 17AAG and related molecules...
  78. ncbi Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis
    I Hostein
    Cancer Research Campaign Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom
    Cancer Res 61:4003-9. 2001
    ....
  79. ncbi Requirement of Hsp90 activity for IkappaB kinase (IKK) biosynthesis and for constitutive and inducible IKK and NF-kappaB activation
    Meike Broemer
    Max Delbruck Center for Molecular Medicine, Robert Rossle Str 10, 13092 Berlin, Germany
    Oncogene 23:5378-86. 2004
    ..Together, these results define a dual requirement for Hsp90 as a regulator of NF-kappaB signaling by its general involvement in IKK activation and by its role in IKK homeostasis...
  80. 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...
  81. ncbi Interaction of the PAS B domain with HSP90 accelerates hypoxia-inducible factor-1alpha stabilization
    Dorthe M Katschinski
    Cell Physiology Group, Medical Faculty, Martin Luther University Halle, Germany
    Cell Physiol Biochem 14:351-60. 2004
    ....
  82. ncbi Hsp90 & Co. - a holding for folding
    J Buchner
    Institut fur Organische Chemie and Biochemie, Technische Universitat Munchen, Lichtenbergstr 4, 85747 München, Germany
    Trends Biochem Sci 24:136-41. 1999
    ....
  83. ncbi Hsp90 is essential in the filarial nematode Brugia pahangi
    Eileen Devaney
    Parasitology Group, Division of Infection and Immunity, Institute of Comparative Medicine, University of Glasgow, UK
    Int J Parasitol 35:627-36. 2005
    ..Thus, Hsp90 or some of its client proteins may provide novel targets for the chemotherapy of filarial infection...
  84. ncbi Synergistic antileukemic interactions between 17-AAG and UCN-01 involve interruption of RAF/MEK- and AKT-related pathways
    Wentao Jia
    Division of Hematology Oncology, MCV Station Box 230, Virginia Commonwealth University Medical College of Virginia, Richmond, VA 23298, USA
    Blood 102:1824-32. 2003
    ....
  85. ncbi Inhibition of heat shock protein 90 function by 17-allylamino-17-demethoxy-geldanamycin in Hodgkin's lymphoma cells down-regulates Akt kinase, dephosphorylates extracellular signal-regulated kinase, and induces cell cycle arrest and cell death
    Georgios V Georgakis
    Department of Lymphoma and Myeloma, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Clin Cancer Res 12:584-90. 2006
    ....
  86. pmc Acquired resistance to 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) in glioblastoma cells
    Nathalie Gaspar
    Signal Transduction and Molecular Pharmacology Team, Cancer Research UK Centre for Cancer The Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom
    Cancer Res 69:1966-75. 2009
    ..In conclusion, low NQO1 activity is a likely mechanism of acquired resistance to 17-AAG in GB, melanoma, and, possibly, other tumor types. Such resistance can be overcome with novel HSP90 inhibitors...
  87. ncbi Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study
    Shanu Modi
    Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    J Clin Oncol 25:5410-7. 2007
    ..This phase I study examined whether a heat shock protein (Hsp) 90 inhibitor tanespimycin (17-AAG; KOS-953) could be administered safely in combination with trastuzumab at a dose that inhibits Hsp90 function in vivo in lymphocytes...
  88. ncbi Efficacy of Hsp90 inhibition for induction of apoptosis and inhibition of growth in cervical carcinoma cells in vitro and in vivo
    Jörg Schwock
    Department of Laboratory Medicine and Pathobiology, University of Toronto, 610 University Ave, 5th Floor, Rm 203, M5G 2M9, Toronto, ON, Canada
    Cancer Chemother Pharmacol 61:669-81. 2008
    ..In this study we investigated the response of a panel of cervical carcinoma cell lines in vitro and in vivo to determine potential factors that might influence the sensitivity towards Hsp90 inhibition...
  89. 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...
  90. 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...
  91. ncbi Potentiation of chemotherapeutics by the Hsp90 antagonist geldanamycin requires a steady serum condition
    Michael Burkitt
    Division of Gastroenterology, Liverpool University, Liverpool, United Kingdom
    Mol Carcinog 46:466-75. 2007
    ....
  92. ncbi Geldanamycin treatment reduces delayed CA1 damage in mouse hippocampal organotypic cultures subjected to oxygen glucose deprivation
    Yi Bing Ouyang
    Department of Anesthesia, Grant Building S272, Stanford University School of Medicine, Stanford, CA 94305 5117, USA
    Neurosci Lett 380:229-33. 2005
    ..Staining with ubiquitin to identify protein aggregates revealed reduced redistribution of ubiquitin, consistent with reduced protein aggregation likely due at least in part to induction of Hsp70 by GA...
  93. ncbi Differential effects of Hsp90 inhibition on protein kinases regulating signal transduction pathways required for myoblast differentiation
    Bo Geon Yun
    Department of Biochemistry and Molecular Biology, 246 NRC, Oklahoma State University, Stillwater, OK 74078 3035, USA
    Exp Cell Res 307:212-23. 2005
    ....
  94. ncbi Geldanamycin restores a defective heat shock response in vivo
    K F Winklhofer
    Department of Cellular Biochemistry, , D-82152 Martinsried, Germany
    J Biol Chem 276:45160-7. 2001
    ..Thus, our studies show that a defective stress response can be pharmacologically restored and suggest that the HSF1 deactivation pathway may play an important role in the regulation of Hsp expression...
  95. ncbi Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies
    Udai Banerji
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Rd, Sutton, Surrey SM2 5NG, UK
    J Clin Oncol 23:4152-61. 2005
    ..To study the toxicity and pharmacokinetic-pharmacodynamic profile of 17-allylamino, 17- demethoxygeldanamycin (17-AAG) and to recommend a dose for phase II trials...
  96. ncbi Toxoplasma gondii Hsp90 is a potential drug target whose expression and subcellular localization are developmentally regulated
    Pablo C Echeverria
    Laboratorio de Parasitologia Molecular, UB2, IIB INTECH, CONICET UNSAM, Camino de Circunvalación Laguna Km 6, C C 164, B7130IIWA Chascomús, Prov Buenos Aires, Argentina
    J Mol Biol 350:723-34. 2005
    ..These results thus suggest Hsp90 may play a role in stage switch...
  97. ncbi Involvement of human heat shock protein 90 alpha in nicotine-induced apoptosis
    Yu ping Wu
    Department of Biochemistry, School of Medicine, Chiba University, Chiba City, Chiba, Japan
    Int J Cancer 100:37-42. 2002
    ..Thus, it was suggested that nicotine induces apoptosis, possibly via Hsp90 alpha expression, in human cells tested...
  98. ncbi Hsp90 inhibitor 17-AAG reduces ErbB2 levels and inhibits proliferation of the trastuzumab resistant breast tumor cell line JIMT-1
    Barbara Zsebik
    Department of Biophysics and Cell Biology, Faculty of Medicine, Medical and Health Science Centre, University of Debrecen, Debrecen, Hungary
    Immunol Lett 104:146-55. 2006
    ....
  99. pmc Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy
    Ami Citri
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    EMBO J 21:2407-17. 2002
    ..Based upon a model for drug-induced degradation of ErbB-2, we propose a general strategy for selective destruction of oncoproteins by targeting their interaction with molecular chaperones...
  100. ncbi 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...
  101. ncbi Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin prevents synovial sarcoma proliferation via apoptosis in in vitro models
    Jefferson Terry
    Genetic Pathology Evaluation Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
    Clin Cancer Res 11:5631-8. 2005
    ....

Research Grants50

  1. SYNTHESIS OF BIOACTIVE CYCLAMS, BISCYCLAMS AND COMPLEXES
    LOUIS HEGEDUS; Fiscal Year: 1999
    ..Rapid, efficient, high yield synthesis of these new classes of macrocyclic compound and complexes will be the primary focus of the proposed research. ..
  2. SYNTHESES OF MACROCYCLIC POLYAMINE LACTAMS
    HARRY WASSERMAN; Fiscal Year: 1990
    The object of the proposed research will be to develop new methods for the synthesis of macrocyclic lactams, particularly polyamine lactams. Among the members of this group are the spermine and spermidine alkaloids...
  3. 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. ..
  4. 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. ..
  5. FP Assay for Isolation of Hsp90 Inhibitors (RMI)
    Gabriela Chiosis; Fiscal Year: 2005
    ....
  6. 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]..
  7. Assays for rapid identification of Hsp70 modulators
    Gabriela Chiosis; Fiscal Year: 2008
    ..abstract_text> ..
  8. 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. ..
  9. CONTROL OF FIBRINOLYTIC PATHWAYS IN LUNG DISEASE
    Sreerama Shetty; Fiscal Year: 2004
    ..abstract_text> ..
  10. Modulation of K channels in renal collecting duct
    Wen Hui Wang; Fiscal Year: 2007
    ....
  11. 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]..
  12. 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. ..
  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. 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. ..
  15. Molecular Modulators of Breast-Bone Metastasis
    John Price; Fiscal Year: 2004
    ..This proposal represents a unique opportunity to identify novel modulators of breast-bone metastasis. ..
  16. HTS Assays for Hsp90 Inhibitors
    BRIAN BLAGG; Fiscal Year: 2007
    ..The therapeutic potential of these compounds could be immense, as subsequent modification of these lead compounds should lead to the development of novel high-affinity Hsp90 antagonists for the treatment of cancer. ..
  17. Genetic analysis of Cryptococcus neoformans virulence
    Joseph Heitman; Fiscal Year: 2009
    ..These studies will enable a genome-wide definition of the gene set contributing to virulence of this common human fungal pathogen. ..
  18. REGULATION OF PULMONARY RESISTANCE VESSELS
    Judy Aschner; Fiscal Year: 2002
    ....
  19. GPCR signaling cascades in Cryptococcus neoformans
    Joseph Heitman; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  20. MECHANISMS OF PROTEIN ACCUMULATION IN RENAL HYPERTROPHY
    Harold Franch; Fiscal Year: 2002
    ..It should also lay the ground work for further investigations into the mechanisms behind renal hypertrophy. ..
  21. 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. ..
  22. 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. ..
  23. Purchase of a 400 MHz Multi-Nuclear NMR Spectrometer
    JOSEPH RICE; Fiscal Year: 2008
    ..The availability of a high resolution multi-nuclear NMR spectrometer is an essential tool for determining the chemical structures of these compounds and advancing these research efforts. [unreadable] [unreadable] [unreadable]..
  24. 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. ..
  25. Development and Evaluation of Purine and Coumarin Based Hsp90 Inhibitors`
    BRIAN BLAGG; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  26. Role of Molecular Chaperones in hERG Processing
    Eckhard Ficker; Fiscal Year: 2008
    ..abstract_text> ..
  27. 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. ..
  28. 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. ..
  29. Receptor Tyrosine Kinases in Mechanotransduction
    Zheng Gen Jin; Fiscal Year: 2009
    ..In this pathway, VEGFR2 may emerge as a central mediator for laminar flow atheroprotective effects, which will provide new insight into the prevention of atherosclerotic vascular disease. ..
  30. The Urokinase-CD87 System in Macrophage Activation
    Robert Sitrin; Fiscal Year: 2004
    ....
  31. 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. ..
  32. Airway muscle tone, RhoA & Cytoskeletal remodeling
    CAROL HIRSHMAN; Fiscal Year: 2007
    ....
  33. Hsp90, NOS3 and Cardioprotection
    Yang Shi; Fiscal Year: 2009
    ..abstract_text> ..
  34. Transcriptional Profiling in Diabetic Nephropathy.
    Michael Simonson; Fiscal Year: 2003
    ..This pilot project will test the feasibility of transcription profiling to identify novel target genes for future mechanistic investigations into glomerular remodeling in diabetic nephropathy. ..
  35. 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. ..
  36. 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. ..
  37. 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. ..
  38. 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. ..
  39. 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. ..
  40. Protein synthesis control by vesicular stomatits virus
    John Connor; Fiscal Year: 2004
    ..These project is designed to develop an independent research program focused on discovering more about mechanisms of both viral and host protein translation with an interest in applying the lessons learned to cancer therapy. ..
  41. Biochemical Effects of Disrupting HSP90
    Charles Erlichman; Fiscal Year: 2004
    ....
  42. 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. ..
  43. 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]..
  44. ANDROGEN RECEPTOR DEGRADATION
    Avrom Caplan; Fiscal Year: 2006
    ..abstract_text> ..
  45. Defibrotide for the treatment of severe hepatic veno-cc*
    Paul Richardson; Fiscal Year: 2007
    ..Abstract Not Provided ..
  46. Brain Manganese Deposition in High Risk Neonates
    Judy Aschner; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  47. IMPACT OF AH RECEPTOR DEGRADATION IN VIVO AND IN VITRO
    RICHARD POLLENZ; Fiscal Year: 2005
    ..abstract_text> ..
  48. 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]..
  49. Control of elF4F complex by Vesicular Stomatitis Virus
    John Connor; Fiscal Year: 2007
    ....
  50. Canine model for assessing CNS access P-gp substrates
    KATRINA MEALEY; Fiscal Year: 2005
    ....