macrocyclic lactams

Summary

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

Top Publications

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

Research Grants

Detail Information

Publications209 found, 100 shown here

  1. 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...
  2. 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...
  3. 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...
  4. 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...
  5. 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...
  6. 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...
  7. 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...
  8. 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...
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. 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
    ....
  14. 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...
  15. 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...
  16. 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
    ....
  17. 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...
  18. 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
    ....
  19. 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...
  20. 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...
  21. 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...
  22. 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...
  23. 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...
  24. 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...
  25. 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...
  26. 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...
  27. 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...
  28. 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
    ....
  29. 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...
  30. 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...
  31. 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...
  32. 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...
  33. 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...
  34. 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...
  35. 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
    ....
  36. 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...
  37. 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...
  38. doi 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...
  39. 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...
  40. 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...
  41. 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...
  42. 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...
  43. 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...
  44. 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
    ....
  45. 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...
  46. 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...
  47. 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
    ....
  48. 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...
  49. 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...
  50. 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...
  51. 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
    ....
  52. 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
    ....
  53. 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
    ....
  54. 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...
  55. 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
    ....
  56. 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...
  57. 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...
  58. 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...
  59. 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
    ....
  60. 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...
  61. 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
    ....
  62. 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
    ....
  63. ncbi Formation of 17-allylamino-demethoxygeldanamycin (17-AAG) hydroquinone by NAD(P)H:quinone oxidoreductase 1: role of 17-AAG hydroquinone in heat shock protein 90 inhibition
    Wenchang Guo
    Department of Pharmaceutical Sciences, School of Pharmacy and Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado
    Cancer Res 65:10006-15. 2005
    ..In conclusion, these studies have shown that reduction of 17-AAG by NQO1 generates 17-AAGH2, a relatively stable hydroquinone that exhibits superior Hsp90 inhibition...
  64. 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...
  65. ncbi Hsp90: an emerging target for breast cancer therapy
    Jason Beliakoff
    Department of Urology, Stanford University School of Medicine, CA, USA
    Anticancer Drugs 15:651-62. 2004
    ..Given the redundancy and complexity of the molecular abnormalities present in most breast cancers, the ability of Hsp90 inhibitors to alter the activity of multiple oncogenic targets may prove of unique therapeutic benefit...
  66. 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
    ....
  67. 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...
  68. 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...
  69. ncbi The heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin, enhances osteoclast formation and potentiates bone metastasis of a human breast cancer cell line
    John T Price
    Tumour Cell Migration and Metastasis Laboratory, St Vincent s Institute, Melbourne, Vistoria, Australia
    Cancer Res 65:4929-38. 2005
    ..These data suggest an important contraindication to the Hsp90 targeted cancer therapy currently undergoing clinical trial...
  70. 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
    ....
  71. ncbi Phase I pharmacokinetic-pharmacodynamic study of 17-(allylamino)-17-demethoxygeldanamycin (17AAG, NSC 330507), a novel inhibitor of heat shock protein 90, in patients with refractory advanced cancers
    Ramesh K Ramanathan
    Molecular Therapeutics Drug Discovery Program, Biostatistics Department, Graduate School of Public Health, and Biostatistics Facility, University of Pittsburgh Cancer Institute, PA 15232, USA
    Clin Cancer Res 11:3385-91. 2005
    ..We did a phase I study of 17AAG to establish the dose-limiting toxicity and maximum tolerated dose and to characterize 17AAG pharmacokinetics and pharmacodynamics...
  72. 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...
  73. 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
    ....
  74. 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...
  75. 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...
  76. pmc The physical association of multiple molecular chaperone proteins with mutant p53 is altered by geldanamycin, an hsp90-binding agent
    L Whitesell
    Department of Pediatrics and Steele Memorial Children s Research Center, University of Arizona, Tucson 85724, USA
    Mol Cell Biol 18:1517-24. 1998
    ..GA did not, however, appear to restore wild-type transcriptional activating activity to mutant p53 proteins in either A1-5 cells or human breast cancer cell lines...
  77. 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...
  78. ncbi A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells
    G Chiosis
    Program in Cell Biology and Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA
    Chem Biol 8:289-99. 2001
    ..e. steroid receptors, Her2, Raf). We have used the structural features of this pocket to design a small molecule inhibitor of Hsp90...
  79. ncbi Modulation of Hsp90 function in neurodegenerative disorders: a molecular-targeted therapy against disease-causing protein
    Masahiro Waza
    Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai Cho, 466 8550 Nagoya, Japan
    J Mol Med (Berl) 84:635-46. 2006
    ..This review will consider our research findings and discuss the possibility of a clinical application of 17-AAG to SBMA and other neurodegenerative diseases...
  80. doi Heat shock protein 90 is important for Sp1 stability during mitosis
    Shao An Wang
    Institute of Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan
    J Mol Biol 387:1106-19. 2009
    ..Taken together, Hsp90 is important for maintaining Sp1 stability during mitosis by the JNK-1-mediated phosphorylation of Sp1 to enable division into daughter cells and to regulate the expression of related genes in the interphase...
  81. pmc A phase 1 dose-escalation study of irinotecan in combination with 17-allylamino-17-demethoxygeldanamycin in patients with solid tumors
    Archie N Tse
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 14:6704-11. 2008
    ..We conducted a phase I study of irinotecan and the Hsp90 inhibitor 17AAG, which can also down-regulate Chk1, in patients with solid tumors...
  82. pmc Expression of a unique drug-resistant Hsp90 ortholog by the nematode Caenorhabditis elegans
    Cynthia L David
    Steele Memorial Children s Research Center, University of Arizona, Tucson, AZ 85724, USA
    Cell Stress Chaperones 8:93-104. 2003
    ..These findings provide new insights into the nature of unusual N-terminal nucleotide-binding fold of Hsp90 and suggest that target-related drug resistance is unlikely to emerge in patients receiving GA-like chemotherapeutic agents...
  83. 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...
  84. pmc Hsp90-mediated assembly of the 26 S proteasome is involved in major histocompatibility complex class I antigen processing
    Taketoshi Yamano
    Laboratory for Immunochaperones, Research Center for Allergy and Immunology RCAI, RIKEN Yokohama Inst, Yokohama 230 0045, Japan
    J Biol Chem 283:28060-5. 2008
    ..Our results indicate that hsp90 facilitates MHC class I antigen processing through epitope production in a complex of the 26 S proteasome...
  85. ncbi Heat shock protein-90 (Hsp90) acts as a repressor of peroxisome proliferator-activated receptor-alpha (PPARalpha) and PPARbeta activity
    Wasana K Sumanasekera
    Center for Molecular Toxicology and Carcinogenesis and Department of Veterinary Science, The Pennsylvania State University, University Park, Pennsylvania 16802, USA
    Biochemistry 42:10726-35. 2003
    ..Thus, we describe the chaperone complex as being a regulator of PPARalpha and PPARbeta activity and have identified a novel, subtype-specific, inhibitory role for Hsp90...
  86. ncbi Tyrosine phosphorylation of HSP90 within the P2X7 receptor complex negatively regulates P2X7 receptors
    Elena Adinolfi
    Institute of Molecular Physiology, Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom
    J Biol Chem 278:37344-51. 2003
    ..We conclude that selective tyrosine phosphorylation of P2X7 receptor-associated HSP90 may act as a negative regulator of P2X7 receptor complex formation and function...
  87. ncbi 17-(Allylamino)-17-demethoxygeldanamycin activity in human melanoma models
    Angelika M Burger
    Tumor Biology Center, Albert Ludwigs University of Freiburg, Freiburg, Germany
    Anticancer Drugs 15:377-87. 2004
    ..g. with tumor regressions) to 17-AAG may be associated with modulation of Hsp90 expression. The expression of this target should be followed in clinical studies with 17-AAG...
  88. 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...
  89. 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
    ....
  90. ncbi Sensitivity of mature Erbb2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp90
    W Xu
    Department of Cell and Cancer Biology, Medicine Branch, NCI, National Institutes of Health, Rockville, Maryland 20850, USA
    J Biol Chem 276:3702-8. 2001
    ..These data suggest that Hsp90 uniquely stabilizes ErbB2 via interaction with its kinase domain and that GA stimulates ErbB2 degradation secondary to disruption of ErbB2/Hsp90 association...
  91. ncbi The anti-proliferative effect of inhibitor of telomerase on cultured retinal pigment epithelial cells
    Y Xiang
    Department of Ophthalmology, Xiehe Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022
    J Tongji Med Univ 21:174-6. 2001
    ..It was concluded that telomerase and Hsp90 can promote the proliferation of the cultured RPE cells, while the inhibitor of them can induce apoptosis and inhibit the growth of the RPE cells...
  92. 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...
  93. ncbi In vitro detection of differential and cell-specific hepatobiliary toxicity induced by geldanamycin and 17-allylaminogeldanamycin using dog liver slices
    Khalid Amin
    SRI International, Menlo Park, California 94025, USA
    Toxicol Sci 87:442-50. 2005
    ..Dog liver slices can thus be used to evaluate species-, compound-, and concentration-dependent differences in toxicity...
  94. ncbi Heat shock protein 90 indirectly regulates ERK activity by affecting Raf protein metabolism
    Fei Dou
    Department of Genetics and Development Biology, Southeast University Medical School, Nanjing 210009, China
    Acta Biochim Biophys Sin (Shanghai) 37:501-5. 2005
    ..Treating cells with Hsp90 inhibitors facilitates Raf degradation, thereby down-regulating the activity of ERK...
  95. ncbi Synergistic interactions between DMAG and mitogen-activated protein kinase kinase 1/2 inhibitors in Bcr/abl+ leukemia cells sensitive and resistant to imatinib mesylate
    Tri K Nguyen
    Department of Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA
    Clin Cancer Res 12:2239-47. 2006
    ....
  96. ncbi Induction of the hypoxia-inducible factor system by low levels of heat shock protein 90 inhibitors
    Nadia O Ibrahim
    Cell Physiology Group, Medical Faculty, Martin Luther University Halle, Halle, Germany
    Cancer Res 65:11094-100. 2005
    ..In summary, these results suggest that dosage will be a critical factor in the treatment of tumor patients with HSP90 inhibitors...
  97. ncbi The topoisomerase II-Hsp90 complex: a new chemotherapeutic target?
    Catherine R Barker
    The Henry Wellcome Laboratory of Molecular and Cellular Gastroenterology, Division of Gastroenterology, School of Clinical Sciences, The University of Liverpool, Liverpool, United Kingdom
    Int J Cancer 118:2685-93. 2006
    ....
  98. ncbi AEG3482 is an antiapoptotic compound that inhibits Jun kinase activity and cell death through induced expression of heat shock protein 70
    Amir H Salehi
    Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Quebec, Canada
    Chem Biol 13:213-23. 2006
    ..These studies establish that AEG3482 inhibits JNK activation and apoptosis by a mechanism involving induced expression of HSP proteins...
  99. ncbi Identification of AHBA biosynthetic genes related to geldanamycin biosynthesis in Streptomyces hygroscopicus 17997
    Weiqing He
    Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Tiantan Xili No 1, Beijing, 100050, China
    Curr Microbiol 52:197-203. 2006
    ..This is the first report on the AHBA biosynthetic gene cluster in a geldanamycin-producing strain...
  100. pmc Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage
    Catherine R Barker
    The Henry Wellcome Laboratory of Molecular and Cellular Gastroenterology, Division of Gastroenterology, School of Clinical Sciences, University of Liverpool, Crown Street, Liverpool L69 3BX, UK
    Nucleic Acids Res 34:1148-57. 2006
    ....
  101. ncbi Involvement of calcium in the differential induction of heat shock protein 70 by heat shock protein 90 inhibitors, geldanamycin and radicicol, in human non-small cell lung cancer H460 cells
    Yuo Sheng Chang
    Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan 30013, Republic of China
    J Cell Biochem 97:156-65. 2006
    ..Taken together, our findings suggest that differential calcium signaling may account for the differential induction of HSP and the action of GA and RA...

Research Grants119 found, 100 shown here

  1. SYNTHESIS OF B-LACTAM ANTIBIOTICS AND MACROCYCLIC LACTAM
    HARRY WASSERMAN; Fiscal Year: 1980
    ..Beta-Lactams will also be employed as intermediates in the synthesis of macrocyclic lactams. It has recently been found that systems markedly different in structure from the penicillins and ..
  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. ORGANOMETALLIC SYNTHESES OF BIOACTIVE COMPOUND
    LOUIS HEGEDUS; Fiscal Year: 1993
    ..This ability is simply unavailable using conventional methodology...
  4. ORGANOMETALLIC SYNTHESES OF BIOACTIVE COMPOUNDS
    LOUIS HEGEDUS; Fiscal Year: 1992
    ..This ability is simply unavailable using conventional methodology...
  5. 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. ..
  6. NOVEL APPROACHES TO THE CYCLOPEPTIDE ALKALOIDS
    Bruce Lipshutz; Fiscal Year: 1980
    ..Particularly intriguing is the extension of these concepts to the preparation of macrocyclic lactams and lactones...
  7. Assays for rapid identification of Hsp70 modulators
    Gabriela Chiosis; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  8. Hsp90 inhibitors as suppressors of protein misfolding toxicity
    Gabriela Chiosis; Fiscal Year: 2007
    ..In conclusion, Hsp90- interfering drugs represent a potential novel class of drugs to promote the survival of neurons and open up a promising approach to the treatment of neurodegenerative diseases. [unreadable] [unreadable] [unreadable]..
  9. 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. ..
  10. Assays for rapid identification of Hsp70 modulators
    Gabriela Chiosis; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  11. Assays for rapid identification of Hsp70 modulators
    Gabriela Chiosis; Fiscal Year: 2008
    ..abstract_text> ..
  12. FP Assay for Isolation of Hsp90 Inhibitors (RMI)
    Gabriela Chiosis; Fiscal Year: 2005
    ....
  13. 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. ..
  14. 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]..
  15. CONTROL OF FIBRINOLYTIC PATHWAYS IN LUNG DISEASE
    Sreerama Shetty; Fiscal Year: 2002
    ..This work may suggest new therapeutic approaches to a variety of inflammatory or neoplastic lung diseases for which current therapy is often unsatisfactory. ..
  16. CONTROL OF FIBRINOLYTIC PATHWAYS IN LUNG DISEASE
    Sreerama Shetty; Fiscal Year: 2000
    ..This work may suggest new therapeutic approaches to a variety of inflammatory or neoplastic lung diseases for which current therapy is often unsatisfactory. ..
  17. 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. ..
  18. CONTROL OF FIBRINOLYTIC PATHWAYS IN LUNG DISEASE
    Sreerama Shetty; Fiscal Year: 1999
    ..This work may suggest new therapeutic approaches to a variety of inflammatory or neoplastic lung diseases for which current therapy is often unsatisfactory. ..
  19. Regulation of Lung Epithelial Fibrinolysis by Urokinase
    Sreerama Shetty; Fiscal Year: 2003
    ..This information could hasten the development of new, mechanism-based interventions for lung disorders, including acute lung injury or lung neoplasia. ..
  20. CONTROL OF FIBRINOLYTIC PATHWAYS IN LUNG DISEASE
    Sreerama Shetty; Fiscal Year: 2001
    ..This work may suggest new therapeutic approaches to a variety of inflammatory or neoplastic lung diseases for which current therapy is often unsatisfactory. ..
  21. Hsp90 as a Target for the Treatment of Childhood Cancer
    Rochelle Bagatell; Fiscal Year: 2007
    ..Upon completion of the award period, Dr. Bagatell will be well prepared to move forward as an independent investigator. ..
  22. CONTROL OF FIBRINOLYTIC PATHWAYS IN LUNG DISEASE
    Sreerama Shetty; Fiscal Year: 2004
    ..abstract_text> ..
  23. Regulation of Lung Epithelial Fibrinolysis by Urokinase
    Sreerama Shetty; Fiscal Year: 2004
    ..This information could hasten the development of new, mechanism-based interventions for lung disorders, including acute lung injury or lung neoplasia. ..
  24. Regulation of Lung Epithelial Fibrinolysis by Urokinase
    Sreerama Shetty; Fiscal Year: 2002
    ..This information could hasten the development of new, mechanism-based interventions for lung disorders, including acute lung injury or lung neoplasia. ..
  25. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    Wen Hui Wang; Fiscal Year: 2002
    ..The effect of PGE2 has relevance to Bartter's Syndrome where hyperprostaglandinemia is prominent and inhibition of prostaglandin production reverses partially the physiological consequences of impaired TAL function. ..
  26. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    Wen Hui Wang; Fiscal Year: 2002
    ..The effect of PGE2 has relevance to Bartter's Syndrome where hyperprostaglandinemia is prominent and inhibition of prostaglandin production reverses partially the physiological consequences of impaired TAL function. ..
  27. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    Wen Hui Wang; Fiscal Year: 2007
    ..Specific Aim 2 To examine whether mono-ubiquitination of ROMK channels is regulated by PKA and PTK. Specific aim 3 To explore the role of CD63 in mediating ROMK1 tyrosine phosphorylation and mono-ubiquitination. ..
  28. MODULATION OF K+ CHANNELS IN RENAL COLLECTING DUCT
    Wen Hui Wang; Fiscal Year: 2003
    ..Since the studies are conducted on freshly isolated CCD, the results will provide information essential for understanding the role of NO in the regulation of Na+ and K+ transport in the CCD. ..
  29. Targeting Cell Cycle Checkpoints in Cancer Therapeutics
    Archie Tse; Fiscal Year: 2007
    ..The proposed studies are expected to provide insights of how checkpoint defects in tumors can be exploited to render them more susceptible to combined treatment with chemotherapy and checkpoint inhibitors such as 17AAG. ..
  30. 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]..
  31. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    Wen Hui Wang; Fiscal Year: 2003
    ..The effect of PGE2 has relevance to Bartter's Syndrome where hyperprostaglandinemia is prominent and inhibition of prostaglandin production reverses partially the physiological consequences of impaired TAL function. ..
  32. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    WenHui Wang; Fiscal Year: 2004
    ..The effect of PGE2 has relevance to Bartter's Syndrome where hyperprostaglandinemia is prominent and inhibition of prostaglandin production reverses partially the physiological consequences of impaired TAL function. ..
  33. The Role of Selective HDAC Enzymes in Drug Sensitivity
    Pamela Munster; Fiscal Year: 2007
    ..In pre- and post-treatment tumor samples, we will determine which HDACs are involved in the cellular effects induced by the HDACi and which HDACs may predict response. ..
  34. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    Wen Hui Wang; Fiscal Year: 2001
    ..The effect of PGE2 has relevance to Bartter's Syndrome where hyperprostaglandinemia is prominent and inhibition of prostaglandin production reverses partially the physiological consequences of impaired TAL function. ..
  35. 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. ..
  36. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    Wen Hui Wang; Fiscal Year: 2003
    ..The effect of PGE2 has relevance to Bartter's Syndrome where hyperprostaglandinemia is prominent and inhibition of prostaglandin production reverses partially the physiological consequences of impaired TAL function. ..
  37. Modulation of K channels in renal collecting duct
    Wen Hui Wang; Fiscal Year: 2005
    ....
  38. SYNTHESIS OF MDR REVERSING POLYENES
    MERRITT ANDRUS; Fiscal Year: 2002
    ..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. ..
  39. Modulation of K channels in renal collecting duct
    Wen Hui Wang; Fiscal Year: 2005
    ....
  40. Modulation of K channels in renal collecting duct
    Wen Hui Wang; Fiscal Year: 2006
    ....
  41. Modulation of K channels in renal collecting duct
    Wen Hui Wang; Fiscal Year: 2004
    ....
  42. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    Wen Hui Wang; Fiscal Year: 2006
    ..Specific Aim 2 To examine whether mono-ubiquitination of ROMK channels is regulated by PKA and PTK. Specific aim 3 To explore the role of CD63 in mediating ROMK1 tyrosine phosphorylation and mono-ubiquitination. ..
  43. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    WenHui Wang; Fiscal Year: 2009
    ..Specific Aim 2 To examine whether mono-ubiquitination of ROMK channels is regulated by PKA and PTK. Specific aim 3 To explore the role of CD63 in mediating ROMK1 tyrosine phosphorylation and mono-ubiquitination. ..
  44. 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. ..
  45. SYNTHESIS OF MDR REVERSING POLYENES
    MERRITT ANDRUS; Fiscal Year: 1999
    ..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. ..
  46. MODULATION OF K+ CHANNELS IN RENAL COLLECTING DUCT
    Wen Hui Wang; Fiscal Year: 1999
    ..Since the studies are conducted on freshly isolated CCD, the results will provide information essential for understanding the role of NO in the regulation of Na+ and K+ transport in the CCD. ..
  47. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    Wen Hui Wang; Fiscal Year: 2005
    ..Specific Aim 2 To examine whether mono-ubiquitination of ROMK channels is regulated by PKA and PTK. Specific aim 3 To explore the role of CD63 in mediating ROMK1 tyrosine phosphorylation and mono-ubiquitination. ..
  48. MODULATION OF K+ CHANNELS IN RENAL COLLECTING DUCT
    Wen Hui Wang; Fiscal Year: 2000
    ..Since the studies are conducted on freshly isolated CCD, the results will provide information essential for understanding the role of NO in the regulation of Na+ and K+ transport in the CCD. ..
  49. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    Wen Hui Wang; Fiscal Year: 2002
    ..The effect of PGE2 has relevance to Bartter's Syndrome where hyperprostaglandinemia is prominent and inhibition of prostaglandin production reverses partially the physiological consequences of impaired TAL function. ..
  50. MODULATION OF K+ CHANNELS IN RENAL COLLECTING DUCT
    Wen Hui Wang; Fiscal Year: 2002
    ..Since the studies are conducted on freshly isolated CCD, the results will provide information essential for understanding the role of NO in the regulation of Na+ and K+ transport in the CCD. ..
  51. Modulation of K channels in renal collecting duct
    Wen Hui Wang; Fiscal Year: 2007
    ....
  52. SYNTHESIS OF MDR REVERSING POLYENES
    MERRITT ANDRUS; Fiscal Year: 2001
    ..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. ..
  53. MODULATION OF K+ CHANNELS IN RENAL COLLECTING DUCT
    Wen Hui Wang; Fiscal Year: 2001
    ..Since the studies are conducted on freshly isolated CCD, the results will provide information essential for understanding the role of NO in the regulation of Na+ and K+ transport in the CCD. ..
  54. Targeting Cell Cycle Checkpoints in Cancer Therapeutics
    Archie Tse; Fiscal Year: 2008
    ..The proposed studies are expected to provide insights of how checkpoint defects in tumors can be exploited to render them more susceptible to combined treatment with chemotherapy and checkpoint inhibitors such as 17AAG. ..
  55. MODULATION AND REGULATION OF ROMK CHANNELS IN KIDNEY
    Wen Hui Wang; Fiscal Year: 2008
    ..Specific Aim 2 To examine whether mono-ubiquitination of ROMK channels is regulated by PKA and PTK. Specific aim 3 To explore the role of CD63 in mediating ROMK1 tyrosine phosphorylation and mono-ubiquitination. ..
  56. SYNTHESIS OF MDR REVERSING POLYENES
    MERRITT ANDRUS; Fiscal Year: 2000
    ..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. ..
  57. 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. ..
  58. ANESTHETICS AND STRESS PROTEINS IN BRAIN CELL INJURY
    Rona Giffard; Fiscal Year: 2003
    ..With improving ability to deliver peptide therapeutics it is possible that a subdomain of HSP70 could be developed into a useful pharmaceutical to improve outcome from stroke. ..
  59. 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. ..
  60. Signal Transduction in the Heart after Cancer Therapy
    Kathleen Gabrielson; Fiscal Year: 2008
    ..The public health significance of this project is that we aim to protect patients from severe cardiotoxic effects of anti-cancer drugs, which in many cases, limits the use of otherwise effective therapies. ..
  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 Eicosanoids: Synthesis and Function
    John Falck; Fiscal Year: 2009
    ..It is the long-term objective of this laboratory to identify these metabolites, develop biochemical and chemical tools to better understand their physiologic roles, and ultimately intervene pharmacologically. ..
  63. Defibrotide for the treatment of severe hepatic veno-cc*
    Paul Richardson; Fiscal Year: 2005
    ..Abstract Not Provided ..
  64. Signal Transduction in the Heart after Cancer Therapy
    Kathleen Gabrielson; Fiscal Year: 2009
    ..The public health significance of this project is that we aim to protect patients from severe cardiotoxic effects of anti-cancer drugs, which in many cases, limits the use of otherwise effective therapies. ..
  65. Novel Eicosanoids: Synthesis and Function
    John Falck; Fiscal Year: 2008
    ..3) Develop isozyme-specific P450 inhibitors using (i) structure based rational design; (ii) computational/molecular modeling; and (iii) library screening. ..
  66. Novel Eicosanoids: Synthesis and Function
    John Falck; Fiscal Year: 2006
    ..3) Develop isozyme-specific P450 inhibitors using (i) structure based rational design; (ii) computational/molecular modeling; and (iii) library screening. ..
  67. Signal Transduction in the Heart after Cancer Therapy
    KATHLEEN LOUISE GABRIELSON; Fiscal Year: 2010
    ..The public health significance of this project is that we aim to protect patients from severe cardiotoxic effects of anti-cancer drugs, which in many cases, limits the use of otherwise effective therapies. ..
  68. Defibrotide for the treatment of severe hepatic veno-cc*
    Paul Richardson; Fiscal Year: 2007
    ..Abstract Not Provided ..
  69. Signal Transduction in the Heart after Cancer Therapy
    Kathleen Gabrielson; Fiscal Year: 2009
    ..The public health significance of this project is that we aim to protect patients from severe cardiotoxic effects of anti-cancer drugs, which in many cases, limits the use of otherwise effective therapies. ..
  70. Brain Manganese Deposition in High Risk Neonates
    Judy Aschner; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  71. Novel Eicosanoids: Synthesis and Function
    John Falck; Fiscal Year: 2007
    ..3) Develop isozyme-specific P450 inhibitors using (i) structure based rational design; (ii) computational/molecular modeling; and (iii) library screening. ..
  72. Prostanoids and hypoxic neonatal pulmonary hypertension
    CANDICE FIKE; Fiscal Year: 2008
    ..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. ..
  73. Hsp90 Chaperone Machine Structure and Function
    Avrom Caplan; Fiscal Year: 2008
    ..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. ..
  74. 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. ..
  75. Hsp90 Chaperone Machine Structure and Function
    Avrom Caplan; Fiscal Year: 2007
    ..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. ..
  76. PHASE I CLINICAL TRIALS OF ANTICANCER AGENTS
    Charles Erlichman; Fiscal Year: 2008
    ..By performing Phase I studies in this fashion, we will facilitate translation of novel preclinical observations into treatments that can be assessed for efficacy in Phase II and Phase III trials. ..
  77. A Low-Dose Decitabine Strategy for Restoring Ovarian Cancer Sensitivity
    Daniela Matei; Fiscal Year: 2008
    ..Successful completion of this study will provide a novel opportunity for treatment for these patients who have otherwise very limited options. ..
  78. Novel Eicosanoids: Synthesis and Function
    John R Falck; Fiscal Year: 2010
    ..It is the long-term objective of this laboratory to identify these metabolites, develop biochemical and chemical tools to better understand their physiologic roles, and ultimately intervene pharmacologically. ..
  79. ANDROGEN RECEPTOR DEGRADATION
    Avrom Caplan; Fiscal Year: 2006
    ..abstract_text> ..
  80. Hsp90/Client Protein Interactions in the Newborn Lung
    Judy Aschner; Fiscal Year: 2006
    ..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. ..
  81. Prostanoids and hypoxic neonatal pulmonary hypertension
    CANDICE FIKE; Fiscal Year: 2002
    ..These studies should provide important information for improving treatment of infants with pulmonary hypertension. ..
  82. NOVEL EICOSANOIDS: ANALYSIS, SYNTHESIS, AND FUNCTION
    John Falck; Fiscal Year: 2001
    ..and (e) elucidation of the P450 active site ..
  83. NOVEL EICOSANOIDS: ANALYSIS, SYNTHESIS, AND FUNCTION
    John Falck; Fiscal Year: 2000
    ..and (e) elucidation of the P450 active site ..
  84. REGULATION OF PULMONARY RESISTANCE VESSELS
    Judy Aschner; Fiscal Year: 2000
    ....
  85. FLOW SHEAR INDUCED NF-KB MEDIATED REGULATION
    Sumathy Mohan; Fiscal Year: 2000
    ..Understanding of NF- kappaB signaling mechanisms in VCAM-1 regulation can also be applied to other inflammatory conditions. ..
  86. NOVEL EICOSANOIDS--ANALYSIS, SYNTHESIS, AND FUNCTION
    John Falck; Fiscal Year: 1999
    ..and (e) elucidation of the P450 active site. ..
  87. EICOSANOID SYNTHESIS
    John Falck; Fiscal Year: 1991
    ..In light of the almost universal distribution of cytochrome P-450 in mammalian tissues, this work will have profound implications for our understanding of fatty acid metabolism and its relationship to homeostasis...
  88. EICOSANOID SYNTHESIS
    John Falck; Fiscal Year: 1992
    ..Given the broad distribution of the new pathways in mammalian tissues, this work will have profound implications for our understanding of fatty acid metabolism and its relationship to homeostasis...
  89. Biochemical Effects of Disrupting HSP90
    Charles Erlichman; Fiscal Year: 2002
    ....
  90. Biochemical Effects of Disrupting HSP90
    Charles Erlichman; Fiscal Year: 2004
    ....
  91. Hsp90/Client Protein Interactions in the Newborn Lung
    Judy Aschner; Fiscal Year: 2005
    ..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. ..