Genomes and Genes
Summary: Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
Publications303 found, 100 shown here
- Thymoquinone: a promising anti-cancer drug from natural sourcesHala Gali-Muhtasib
Department of Biology, American University of Beirut, Beirut, Lebanon
Int J Biochem Cell Biol 38:1249-53. 2006..The combination of TQ with clinically used anti-cancer drugs has led to improvements in their therapeutic index and prevents non-tumor tissues from sustaining chemotherapy-induced damage...
- Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1J 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...
- HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumabShanu Modi
Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Clin Cancer Res 17:5132-9. 2011..On the basis of these data and activity in a phase I study, we conducted a phase II study of 17-AAG (tanespimycin) with trastuzumab in advanced trastuzumab-refractory HER2-positive breast cancer...
- Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the hsp90 chaperoneRongmin 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...
- Dual targeting of HSC70 and HSP72 inhibits HSP90 function and induces tumor-specific apoptosisMarissa V Powers
Signal Transduction and Molecular Pharmacology Team, Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey SM2 5NG, UK
Cancer Cell 14:250-62. 2008..Importantly, simultaneous silencing of HSP70 isoforms in nontumorigenic cell lines does not result in comparable growth arrest or induction of apoptosis, indicating a potential therapeutic window...
- Targeting Hsp90: small-molecule inhibitors and their clinical developmentTony 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....
- RACK1 competes with HSP90 for binding to HIF-1alpha and is required for O(2)-independent and HSP90 inhibitor-induced degradation of HIF-1alphaYe 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...
- Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agentC 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...
- Altered Hsp90 function in cancer: a unique therapeutic opportunityRochelle Bagatell
Department of Pediatrics and Hematology Oncology, Arizona Health Sciences Center, Room 5341, 1501 North Campbell Avenue, Tucson, AZ 85724, USA
Mol Cancer Ther 3:1021-30. 2004....
- Heat shock transcription factor 1-activating compounds suppress polyglutamine-induced neurodegeneration through induction of multiple molecular chaperonesNobuhiro Fujikake
Division of Clinical Genetics, Department of Medical Genetics, Osaka University Graduate School of Medicine, Suita, Osaka 565 0871, Japan
J Biol Chem 283:26188-97. 2008..Our study indicates that induction of multiple molecular chaperones by 17-AAG treatment is a promising therapeutic approach for a wide range of polyQ diseases and possibly other neurodegenerative diseases...
- Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signalingNahed El-Najjar
Department of Biology, American University of Beirut, Beirut, Lebanon
Apoptosis 15:183-95. 2010..These data present evidence linking the pro-oxidant effects of TQ with its apoptotic effects in colon cancer and prove a protective role of MAPK...
- Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum and Trypanosoma evansi and evaluation of its inhibitor as a candidate drugRani Pallavi
Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India
J Biol Chem 285:37964-75. 2010..evansi growth in a mouse model of trypanosomiasis. In all, our biochemical characterization, drug interaction, and animal studies supported Hsp90 as a drug target and its inhibitor as a potential drug against protozoan diseases...
- Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapyWeiwen Ying
Synta Pharmaceuticals Corp, 45 Hartwell Avenue, Lexington, MA 02421, USA
Mol Cancer Ther 11:475-84. 2012....
- Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytesGowrishankar 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...
- The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive targetMelissa L Fishel
Department of Pediatrics Section of Hematology Oncology, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, United States
Mol Aspects Med 28:375-95. 2007..In this review, we will provide an overview of Ape1/Ref-1's activities and explore the potential of this protein as a target in cancer treatment as well as its role in chemoprevention...
- Inhibition of heat shock protein 90 (HSP90) as a therapeutic strategy for the treatment of myeloma and other cancersPaul G Richardson
Dana Farber Cancer Institute, Boston, MA 02115, USA
Br J Haematol 152:367-79. 2011....
- Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilizationY Peng
Molecular Oncology Program, H Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA
J Biol Chem 276:40583-90. 2001..These results suggest that hsp90 recruited by mutant p53 conceals the ARF-binding site on MDM2 and inhibits its ubiquitin-protein isopeptide ligase function, resulting in the stabilization of both mutant p53 and MDM2...
- Evolutionary constraints on chaperone-mediated folding provide an antiviral approach refractory to development of drug resistanceRon Geller
Department of Biological Sciences, Stanford University, Stanford, California 94305, USA
Genes Dev 21:195-205. 2007..We propose that targeting folding of viral proteins may provide a general antiviral strategy that is refractory to development of drug resistance...
- Gene and protein expression profiling of human ovarian cancer cells treated with the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycinAlison Maloney
Haddow Laboratories, Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Surrey, United Kingdom
Cancer Res 67:3239-53. 2007....
- Plasma pharmacokinetics and tissue distribution of 17-(allylamino)-17-demethoxygeldanamycin (NSC 330507) in CD2F1 mice1M 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...
- 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 cytotoxicityKheem 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...
- 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degenerationMasahiro Waza
Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai Cho, Showa Ku, Nagoya 466 8550, Japan
Nat Med 11:1088-95. 2005..17-AAG also mildly induced Hsp70 and Hsp40. 17-AAG would thus provide a new therapeutic approach to SBMA and probably to other related neurodegenerative diseases...
- V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitorsO 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...
- Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumorSebastian 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...
- A novel HSP90 inhibitor delays castrate-resistant prostate cancer without altering serum PSA levels and inhibits osteoclastogenesisFrancois Lamoureux
The Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada
Clin Cancer Res 17:2301-13. 2011..17-Allylamino-17-demethoxy-geldanamycin (17-AAG) has been reported to inhibit tumor growth in various cancers; however, it induces tumor progression in the bone microenvironment...
- Anticancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR-γ pathwayChern Chiuh Woo
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Biochem Pharmacol 82:464-75. 2011....
- Thymoquinone: potential cure for inflammatory disorders and cancerChern Chiuh Woo
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Biochem Pharmacol 83:443-51. 2012..In this review, we summarize the anti-oxidant/anti-inflammatory and anticancer effects of thymoquinone with a focus on its molecular targets, and its possible role in the treatment of inflammatory diseases and cancer...
- Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinomaSubhasis Das
School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal, India
PLoS ONE 7:e46641. 2012..TQ and DG, alone and in combination, inhibit cell proliferation and induce apoptosis in squamous cell carcinoma. The combination of TQ and DG is a potential antineoplastic therapy in this common skin cancer...
- Potent activity of the Hsp90 inhibitor ganetespib in prostate cancer cells irrespective of androgen receptor status or variant receptor expressionSuqin He
Synta Pharmaceuticals Corp, Lexington, MA 02421, USA
Int J Oncol 42:35-43. 2013..Together these data suggest that further investigation of ganetespib as a new therapeutic treatment for prostate cancer patients is warranted...
- Pharmacokinetic-pharmacodynamic relationships for the heat shock protein 90 molecular chaperone inhibitor 17-allylamino, 17-demethoxygeldanamycin in human ovarian cancer xenograft modelsUdai Banerji
Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, United Kingdom
Clin Cancer Res 11:7023-32. 2005..To establish the pharmacokinetic and pharmacodynamic profile of the heat shock protein 90 (HSP90) inhibitor 17-allylamino, 17-demethoxygeldanamycin (17-AAG) in ovarian cancer xenograft models...
- Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycinSilvy da Rocha Dias
The Institute of Cancer Research, Signal Transduction Team, Cancer Research UK Centre for Cell and Molecular Biology, London, United Kingdom
Cancer Res 65:10686-91. 2005..Our data show that B-RAF is an important target for 17-AAG in human cancer...
- Hsp90 inhibition has opposing effects on wild-type and mutant p53 and induces p21 expression and cytotoxicity irrespective of p53/ATM status in chronic lymphocytic leukaemia cellsK Lin
Department of Haematology, Royal Liverpool and Broadgreen University Hospitals Trust, Liverpool, UK
Oncogene 27:2445-55. 2008..In summary, our findings reveal important consequences of inhibiting Hsp90 in CLL cells and strongly support the therapeutic evaluation of Hsp90 inhibitors in poor-prognosis patients with p53 defects...
- Hsp90 inhibitors as novel cancer chemotherapeutic agentsLen 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...
- Pharmacological and toxicological properties of Nigella sativaB H Ali
Department of Veterinary Medicine, King Saud University, Buraydah, Al Gaseem 81999, Saudi Arabia
Phytother Res 17:299-305. 2003..It would appear that the beneficial effects of the use of the seeds and thymoquinone might be related to their cytoprotective and antioxidant actions, and to their effect on some mediators of inflammation...
- Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERGEckhard Ficker
Rammelkamp Center, Case Western Reserve University, Cleveland, Ohio 44109, USA
Circ Res 92:e87-100. 2003..We conclude that Hsp90 and Hsp70 are crucial for the maturation of hERG WT as well as the retention of trafficking-deficient LQT2 mutants. The full text of this article is available online at http://www.circresaha.org...
- Targeting nuclear factor-kappa B activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosisGautam Sethi
Cytokine Research Laboratory, Department of Experimental Therapeutics, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
Mol Cancer Res 6:1059-70. 2008....
- In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysisW 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...
- Hsp90 inhibitors suppress HCV replication in replicon cells and humanized liver miceShin Ichiro Nakagawa
Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3 18 22 Honkomagome, Bunkyo ku, Tokyo 113 8613, Japan
Biochem Biophys Res Commun 353:882-8. 2007..These results suggest that inhibition of Hsp90 could provide a new therapeutic approach to HCV infection...
- Ansamycin antibiotics inhibit Akt activation and cyclin D expression in breast cancer cells that overexpress HER2Andrea 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...
- The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycinT W Schulte
Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 1928, USA
Cancer Chemother Pharmacol 42:273-9. 1998..We therefore examined the biologic effects of 17-allylamino-17-demethoxygeldanamycin (17-AG), an ansamycin derivative with lower in vivo toxicity than GA...
- 17-Allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenograftsDavid B Solit
Program in Cell Biology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
Clin Cancer Res 8:986-93. 2002....
- Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanismHala Gali-Muhtasib
Department of Biology, American University of Beirut, Beirut, Lebanon
Int J Oncol 25:857-66. 2004..The apoptotic effects of TQ are modulated by Bcl-2 protein and are linked to and dependent on p53. Our data support the potential for using the agent TQ for the treatment of colon cancer...
- Epidermal growth factor receptors harboring kinase domain mutations associate with the heat shock protein 90 chaperone and are destabilized following exposure to geldanamycinsTakeshi 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...
- Inhibitors of the HSP90 molecular chaperone: current statusSwee 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...
- Inhibition of hsp90 compromises the DNA damage response to radiationHideaki 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...
- Hsp90 inhibitors reduce influenza virus replication in cell cultureGeoffrey Chase
Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Hermann Herder Strasse 11, D 79104 Freiburg, Germany
Virology 377:431-9. 2008..Hsp90 inhibitors may represent a new class of antiviral compounds against influenza viruses...
- Thymoquinone triggers inactivation of the stress response pathway sensor CHEK1 and contributes to apoptosis in colorectal cancer cellsHala Gali-Muhtasib
Department of Biology, American University of Beirut, Beirut, Lebanon
Cancer Res 68:5609-18. 2008..9-fold risk, univariate Cox regression; Kaplan-Meier, P = 0.04). We suggest that the inhibition of the stress response sensor CHEK1 might contribute to the antineoplastic activity of specific DNA-damaging drugs...
- A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancerElisabeth I Heath
Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA
Clin Cancer Res 14:7940-6. 2008..A two-stage phase II study was conducted to assess the activity and toxicity profile of 17-AAG administered to patients with metastatic, hormone-refractory prostate cancer...
- Therapeutic and diagnostic implications of Hsp90 activationAdeela 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...
- Inhibition of heat shock protein 90 impairs epidermal growth factor-mediated signaling in gastric cancer cells and reduces tumor growth and vascularization in vivoSven 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...
- Regulation of tumor cell mitochondrial homeostasis by an organelle-specific Hsp90 chaperone networkByoung 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...
- Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasomeM 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...
- Heat shock protein 90 homeostasis controls stage differentiation in Leishmania donovaniM 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...
- The heat shock protein 90 of Leishmania donovaniM Wiesgigl
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
Med Microbiol Immunol 190:27-31. 2001..We propose a role for Hsp90 in the feedback control of the cellular stress response and in the control of the parasite's life cycle...
- Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (NSC 707545) in CD2F1 mice and Fischer 344 ratsMerrill J Egorin
Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, PA 15213, USA
Cancer Chemother Pharmacol 49:7-19. 2002..p. and oral delivery; (3) characterize the biliary excretion of 17DMAG after i.v. delivery to rats; and (4) characterize, if possible, any metabolites of 17DMAG observed in plasma, tissue, urine, or bile...
- The molecular chaperone Hsp90 plays a role in the assembly and maintenance of the 26S proteasomeJun 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...
- A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitorsAdeela 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...
- Thymoquinone induces apoptosis through activation of caspase-8 and mitochondrial events in p53-null myeloblastic leukemia HL-60 cellsMohamed A El-Mahdy
Department of Radiology, Ohio State University, Columbus, OH 43210, USA
Int J Cancer 117:409-17. 2005..Activated caspase-8 initiates the release of cytochrome c during TQ-induced apoptosis. Overall, these results offer a potential mechanism for TQ-induced apoptosis in p53-null HL-60 cancer cells...
- Geldanamycin induces heat shock protein 70 and protects against MPTP-induced dopaminergic neurotoxicity in miceHai Ying Shen
Molecular Neuropharmacology Laboratory, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 280:39962-9. 2005....
- Abrogation of heat shock protein 70 induction as a strategy to increase antileukemia activity of heat shock protein 90 inhibitor 17-allylamino-demethoxy geldanamycinFei 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...
- Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90Toru Okamoto
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
EMBO J 25:5015-25. 2006..These results suggest that the complex consisting of NS5A, FKBP8, and Hsp90 plays an important role in HCV RNA replication...
- The heat-shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin suppresses glial inflammatory responses and ameliorates experimental autoimmune encephalomyelitisCinzia Dello Russo
Department of Anesthesiology, University of Illinois, and Jesse Brown Veteran s Affairs Research Division, Chicago, Illinois 60612, USA
J Neurochem 99:1351-62. 2006..Together, these data suggest that HSP90 inhibitors could represent a new approach for therapeutic intervention in autoimmune diseases such as multiple sclerosis...
- Thymoquinone reduces mouse colon tumor cell invasion and inhibits tumor growth in murine colon cancer modelsHala Gali-Muhtasib
Department of Biology, American University of Beirut, Beirut, Lebanon
J Cell Mol Med 12:330-42. 2008..These data should encourage further in vivo testing and support the potential use of TQ as a therapeutic agent in human colorectal cancer...
- Role of the multifunctional DNA repair and redox signaling protein Ape1/Ref-1 in cancer and endothelial cells: small-molecule inhibition of the redox function of Ape1Meihua Luo
Department of Pediatrics Section of Hematology Oncology, Herman B Wells Center for Pediatric Research, Indianapolis, Indiana 46202, USA
Antioxid Redox Signal 10:1853-67. 2008..Here we discuss small-molecule inhibition of Ape1 redox and its effect on both cancer and endothelial cells...
- Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathwaysTingfang Yi
Center for Cancer and Stem Cell Biology, Institute for Bioscience and Technology, Texas A and M University System Health Science Center, 2121 West Holcombe Boulevard, Houston, TX 77030, USA
Mol Cancer Ther 7:1789-96. 2008..Overall, our results indicate that thymoquinone inhibits tumor angiogenesis and tumor growth and could be used as a potential drug candidate for cancer therapy...
- Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migrationGang Ming Zou
Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB 2, M341, Baltimore, MD 21231, USA
Mol Cancer Ther 7:2012-21. 2008..Inhibition of the APE1 redox function through pharmacologic means has the potential to become a promising therapeutic strategy in this disease...
- Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancerSanjeev Banerjee
Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA
Cancer Res 69:5575-83. 2009....
- Apoptosis caused by Hsp90 inhibitor geldanamycin in Leishmania donovani during promastigote-to-amastigote transformation stageQiaoli Li
Bio X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of Education, College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China
Parasitol Res 105:1539-48. 2009..donovani but could not cause stage differentiation in high temperature and that acidic conditions were likely to be crucial for the transformation and survival of the parasite within its human host...
- Embelin induces apoptosis through down-regulation of XIAP in human leukemia cellsRong Hu
Department of Hematology, Shengjing Hospital, China Medical University, 110004, Shenyang, China
Med Oncol 28:1584-8. 2011..Taken together, these findings suggest that embelin results in human leukemia cells apoptosis through caspase-dependent mechanisms involving down-regulation of XIAP...
- Interactions of apurinic/apyrimidinic endonuclease with a redox inhibitor: evidence for an alternate conformation of the enzymeDian Su
Department of Chemistry, Washington University in St Louis, St Louis, Missouri 63130, United States
Biochemistry 50:82-92. 2011..Collectively, our results suggest that APE1 adopts a partially unfolded state, which we propose is the redox active form of the enzyme...
- Gambogic acid, a natural product inhibitor of Hsp90Jason Davenport
Department of Biochemistry and Molecular Biology, 246 Noble Research Center, Oklahoma State University, Stillwater, Oklahoma 74078, United States
J Nat Prod 74:1085-92. 2011..The data obtained have firmly established 1 as a novel Hsp90 inhibitor and have provided evidence of a new site that can be targeted for the development of improved Hsp90 inhibitors...
- Anti-malarial, anti-trypanosomal, and anti-leishmanial activities of jacaranone isolated from Pentacalia desiderabilis (Vell.) Cuatrec. (Asteraceae)Thiago R Morais
Centro de Ciências e Humanidades e Centro de Ciências Biológias e da Saúde, Universidade Presbiteriana Mackenzie, 01302 907, Sao Paulo, SP, Brazil
Parasitol Res 110:95-101. 2012..75 μg/mL) and a selectivity index of 3. The obtained results suggested that jacaranone, as other similar secondary metabolites or synthetic analogs, might be useful tolls for drug design for in vivo studies against protozoan diseases...
- Multicenter phase II trial of the heat shock protein 90 inhibitor, retaspimycin hydrochloride (IPI-504), in patients with castration-resistant prostate cancerWilliam K Oh
Mount Sinai School of Medicine, New York, New York 10029, USA
Urology 78:626-30. 2011..To evaluate clinical activity and safety of retaspimycin hydrochloride (IPI-504) in patients with castration-resistant prostate cancer (CRPC)...
- Identification of heat-shock protein 90 beta in Japanese encephalitis virus-induced secretion proteinsChun Yu Hung
Department of Biomedical Sciences, Chang Gung University, Tao Yuan 33302, Taiwan, ROC
J Gen Virol 92:2803-9. 2011..Our results show that Hsp90β, not Hsp90α, is present in the JEV-induced secretion medium and is required for JEV infectivity in BHK-21 cells...
- Hsp90 inhibitor 17-AAG inhibits progression of LuCaP35 xenograft prostate tumors to castration resistanceKatherine J O'malley
Department of Urology, University of Pittsburgh, Pittsburgh, PA, USA
Prostate 72:1117-23. 2012..This study addresses whether targeting Heat shock protein 90 (HSP90) regulation of androgen receptor (AR) can inhibit prostate cancer progression to castration resistance...
- Thymoquinone inhibits growth and augments 5-fluorouracil-induced apoptosis in gastric cancer cells both in vitro and in vivoXiaofei Lei
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, PR China
Biochem Biophys Res Commun 417:864-8. 2012....
- Hsp90 is required for the activity of a hepatitis B virus reverse transcriptaseJ 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...
- Hsp90 inhibitors block outgrowth of EBV-infected malignant cells in vitro and in vivo through an EBNA1-dependent mechanismXiaoping Sun
Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
Proc Natl Acad Sci U S A 107:3146-51. 2010..These results suggest that Hsp90 inhibitors may be particularly effective for treating EBV-induced diseases requiring the continued presence of the viral genome...
- TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90Guoqing 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...
- Heat-shock protein 90 is essential for stabilization of the hepatitis C virus nonstructural protein NS3Saneyuki Ujino
Department of Life and Environmental Sciences, High Technology Research Center, Research Institute, Chiba Institute of Technology, 2 17 1 Tsudanuma, Narashino, Chiba 275 0016, Japan
J Biol Chem 284:6841-6. 2009..These results suggest that the suppression of HCV RNA replication is due to the destabilization of NS3 in disruption of the Hsp90 chaperone complex by 17-AAG...
- Hsp90 inhibitors, GA and 17AAG, lead to ER stress-induced apoptosis in rat histiocytomaAftab Taiyab
Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500007, India
Biochem Pharmacol 78:142-52. 2009..We conclude that inhibition of Hsp90 leads to ER stress-induced mitochondria-mediated apoptosis and that Bax and Ca(2+) play an important role in mitochondrial damage...
- Protective effect of Nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells deathS H Mousavi
Department of Pharmacology and Pharmacological Research Centre of Medicinal Plants, School of Medicine, Mashhad University of Medical Sciences MUMS, Mashhad, Iran
Cell Mol Neurobiol 30:591-8. 2010..Our findings might raise the possibility of potential therapeutic application of N. sativa extract and TQ for managing cerebral ischemic and neurodegenerative disorders...
- Inhibitory effects of thymoquinone against 20-methylcholanthrene-induced fibrosarcoma tumorigenesisO A Badary
Department of Pharmacology and Toxicology, College of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt
Cancer Detect Prev 25:362-8. 2001..The possible modes of action of TQ may be through its antioxidant activity and interference with the DNA synthesis coupled with enhancement of detoxification processes...
- CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregationLeonard 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...
- Heat-shock protein 90 (Hsp90) as a molecular target for therapy of gastrointestinal cancerChristian Moser
Department of Surgery, University of Regensburg Medical Center, 93042 Regensburg, Germany
Anticancer Res 29:2031-42. 2009..Against this background, the following review focuses on the current preclinical experience and value of targeting Hsp90 for the therapy of gastrointestinal carcinomas...
- Phase I trial of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein inhibitor, administered twice weekly in patients with advanced malignanciesShivaani Kummar
Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
Eur J Cancer 46:340-7. 2010....
- Discovery and development of Hsp90 inhibitors: a promising pathway for cancer therapyJames R Porter
Infinity Pharmaceuticals, Inc, 780 Memorial Drive, Cambridge, MA 02139, USA
Curr Opin Chem Biol 14:412-20. 2010..The most advanced candidates are now in Phase 2 clinical trials and defining the therapeutic window, dosing schedule, and indication are the primary challenges for these potential first-in-class inhibitors...
- Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathwayFeng Li
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Br J Pharmacol 161:541-54. 2010..In the present report, we investigated whether thymoquinone (TQ), the main component isolated from the medicinal plant Nigella sativa, modulated the STAT3 signalling pathway in MM cells...
- Binding of p23 and hsp90 during assembly with the progesterone receptorJ 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...
- A proteomic investigation of ligand-dependent HSP90 complexes reveals CHORDC1 as a novel ADP-dependent HSP90-interacting proteinJacob J Gano
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
Mol Cell Proteomics 9:255-70. 2010..Together these findings suggest that the HSP90 interactome is dynamic with respect to nucleotide and drug ligands and that pharmacological inhibition of HSP90 may stimulate the formation of specific complexes...
- Up-regulation of heat shock protein 27 induces resistance to 17-allylamino-demethoxygeldanamycin through a glutathione-mediated mechanismAndrea K McCollum
Department of Molecular Pharmacology, Mayo Clinic College of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA
Cancer Res 66:10967-75. 2006..Our results suggest that Hsp27 up-regulation has a significant role in 17-AAG resistance, which may be mediated in part through GSH regulation. Clinical modulation of GSH may therefore enhance the efficacy of Hsp90-directed therapy...
- Thymoquinone is a potent superoxide anion scavengerOsama A Badary
Department of Pharmacology and Toxicology, College of Pharmacy, Al Azhar University, Nasr City, Cairo, Egypt
Drug Chem Toxicol 26:87-98. 2003..The results suggest that both TQ and TBHQ have strong antioxidant potentials through scavenging ability of different free radicals. Moreover, the data indicate that TQ is acting mainly as a potent superoxide anion scavenger...
- FLT3 expressing leukemias are selectively sensitive to inhibitors of the molecular chaperone heat shock protein 90 through destabilization of signal transduction-associated kinasesQing Yao
University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, USA
Clin Cancer Res 9:4483-93. 2003..We conducted studies to evaluate the hypothesis that FLT3 is a client of heat shock protein (Hsp) 90 and inhibitors of Hsp90 may be useful for therapy of leukemia...
- Effects of small molecules on chaperone-mediated autophagyPatrick F Finn
Department of Cellular and Molecular Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
Autophagy 1:141-5. 2005..Finally we demonstrate that the glucose-6-phophate dehydrogenase inhibitor, 6-aminonicotinamide, and heat shock protein of 90 kilodaltons inhibitor, geldanamycin, have the ability to activate CMA...
- 17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in an SBMA model mouseKeisuke Tokui
Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai Cho, Showa Ku, Nagoya 466 8550, Japan
Hum Mol Genet 18:898-910. 2009..17-DMAG also significantly induced Hsp70 and Hsp40. Thus, 17-DMAG would exert a therapeutic effect on SBMA via preserved proteasome function...
- Plasmodial heat shock proteins: targets for chemotherapyAddmore Shonhai
Department of Biochemistry and Microbiology, Zululand University, KwaDlangezwa, South Africa
FEMS Immunol Med Microbiol 58:61-74. 2010..The proposed mechanisms of action of these molecules and the pathways they inhibit are discussed...
- Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's diseaseA 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...
- Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cellsNicola 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...
- COMMD1 Promotes pVHL and O2-Independent Proteolysis of HIF-1alpha via HSP90/70Bart 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...
- Rapid glucocorticoid receptor exchange at a promoter is coupled to transcription and regulated by chaperones and proteasomesDiana A Stavreva
Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute Light Imaging Facility, National Institute for Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA
Mol Cell Biol 24:2682-97. 2004..Moreover, our results reveal that longer GR residence times are consistently associated with greater transcriptional output, suggesting a new paradigm in which the rate of rapid exchange provides a means to tune transcriptional levels...
- 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cellsGerard Fumo
National Cancer Institute, Cell and Cancer Biology Branch, 9610 Medical Center Dr, Ste 300, Rockville, MD 20850, USA
Blood 103:1078-84. 2004..These data provide compelling evidence that 17-AAG may be effective in the treatment of c-kit-related diseases including mastocytosis, GISTs, mast cell leukemia, subtypes of acute myelogenous leukemia, and testicular cancer...
- David Ross; Fiscal Year: 2014DESCRIPTION (provided by applicant): Both benzoquinones and naphthoquinones have been found to perturb protein handling and degradation in a variety of cellular systems...
- Arthropod-Based Libraries for High Throughput ScreeningFrank Schroeder; Fiscal Year: 2009..characterized have simple structures (such as straight chain alkenes, carboxylic acids, aldehydes, phenols, benzoquinones), there are also many examples of biologically active alkaloids, isoprenoids (including steroids), and ..
- SYNTHESIS OF BIOLOGICALLY IMPORTANT DIHYDROBENZOFURANSThomas Engler; Fiscal Year: 1991A study is proposed of the Lewis acid catalyzed reactions of various alkenes and cyclopropanes with methoxy-1,4-benzoquinones to selectively yield dihydrobenzofurans A-C and chromans D-F, respectively...
- SECRETIONS OF ARTHROPODSThomas Eisner; Fiscal Year: 2008..Insects are major vectors of disease. An understanding of how insects depend on natural products for regulation of their biotic interactions is of broad applied significance to both medicine and agriculture. [unreadable] [unreadable]..
- PROTON & ELECTRON TRANSFER & ENERGY COUPLING IN SITE ITOMOKO NONE OHNISHI; Fiscal Year: 2010..Using this new strategy, we found that both cluster N2 and flavin can generate superoxide. We will solidify this exciting finding and study its relevance to complex I function under physiological and pathological conditions. ..
- 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. ..
- Regulation of Lung Epithelial Fibrinolysis by UrokinaseSreerama 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. ..
- CONTROL OF FIBRINOLYTIC PATHWAYS IN LUNG DISEASESreerama Shetty; Fiscal Year: 2004..abstract_text> ..
- 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. ..
- FP Assay for Isolation of Hsp90 Inhibitors (RMI)Gabriela Chiosis; Fiscal Year: 2005....
- Assays for rapid identification of Hsp70 modulatorsGabriela Chiosis; Fiscal Year: 2008..abstract_text> ..
- Hsp90 inhibitors as suppressors of protein misfolding toxicityGabriela 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]..
- Potentiation of Topo Inhibitors by the HDACi, SAHAPamela Munster; Fiscal Year: 2007..These findings may be useful in the rational design of future clinical trials involving HDACi. [unreadable] [unreadable]..
- Defibrotide for the treatment of severe hepatic veno-cc*Paul Richardson; Fiscal Year: 2007..Abstract Not Provided ..
- REDOX ACTIVITY OF THE PULMONARY ENDOTHELIAL SURFACEMARILYN MERKER; Fiscal Year: 2008....
- Chemosensitization of Pancreatic Tumors via Inhibition of a DNA BER Enzyme, Ape1Melissa Fishel; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- Potentiation of Topo Inhibitors by HDAC InhibitorsPamela 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. ..
- Modulation of K channels in renal collecting ductWen Hui Wang; Fiscal Year: 2007....
- Reduction of Alkylating Quinones and NitroarenesANTONIO ALEGRIA; Fiscal Year: 2003..Undergraduate students will participate in this project, thus improving their qualifications to pursue biomedical research careers. ..
- SYNTHESIS OF MDR REVERSING POLYENESMERRITT 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. ..
- Arsenic Trioxide Down-Regulates STAT3 Activity in AMLMeir 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. ..
- Salt Absorption by the THAL: Role of NKCC2 traffickingPablo 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. ..
- Enhancing Photodynamic Therapy for Treating Kaposi's SarcomaCharles Gomer; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- Invasion and Angiogenesis in Malignant GliomasDavid Zagzag; Fiscal Year: 2008..Results from these experiments will lead to future strategies designed to inhibit specific molecular components implicated in these critical processes. ..
- Hsp90/Client Protein Interactions in the Newborn LungJudy 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. ..
- SCREENS TO IDENTIFY GAIN OF FUNCTION AH RECEPTOR MUTANTS INVOLVED IN DEGRADATIONRICHARD POLLENZ; Fiscal Year: 2008..e. steroid hormone receptors). [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
- GPCR signaling cascades in Cryptococcus neoformansJoseph Heitman; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- OXIDATIVE DNA DAMAGE AND REPAIR IN CNS CELLSMark Kelley; Fiscal Year: 2003..abstract_text> ..
- TGF-BETAS AND RECEPTORS AND HUMAN BREAST CELLSCarlos Arteaga; Fiscal Year: 2009..Specific Aim 4: To determine if the activated type I TGFbeta receptor (Alk5) synergizes with HER2 (erbB2) in mammary tumorigenesis and whether it negates the therapeutic effect of HER2 inhibitors in vivo. ..
- Synthesis of Macrolides, Steroids, Cyclopentanoids, etc.BARRY TROST; Fiscal Year: 2009..These new synthetic methods apply to many structural types beyond those illustrated and constitutes a significant to gain access to complex molecular targets more easily. ..
- BCI2 Antisense Against Chemoresistance in Elderly AMLGuido Marcucci; Fiscal Year: 2003..It is expected that the analysis of the clinical and correlative laboratory results will support testing of this combination in a phase III setting. ..
- MULTIDISCIPLINARY TRAINING IN EXPERIMENTAL HEMATOLOGYScott Kaufmann; Fiscal Year: 2005..This program is a natural outgrowth of existing training opportunities in hematology, but will provide better preparation for laboratory research in hematological diseases. (End of Abstract) ..
- Lipid Raft Microdomains in Neutrophil FunctionROBERT 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. ..
- Genetics of mating and fruiting in Cryptococcus neoformansJoseph Heitman; Fiscal Year: 2010..neoformans and C. gattii applicable to development of treatment approaches, diagnostics, or environmental interventions to reduce exposure to infectious spores. ..
- Role of Calcineurin in Fungal VirulenceJoseph 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. ..
- Hsp90, NOS3 and CardioprotectionYang Shi; Fiscal Year: 2009..abstract_text> ..
- Aging and brain 5-lipoxygenaseHari Manev; Fiscal Year: 2010..The proposed experiments may corroborate the hypothesis that epigenetic mechanisms are involved in brain aging. ..
- A Metabolomic Approach to Discovering Biomarkers for ADPKDRobert 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. ..
- Hsp90 Chaperone Machine Structure and FunctionAvrom 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. ..
- TERPENE CYCLASES: FUNCTIONAL DOMAINS AND STRUCTURESJOSEPH NOEL; Fiscal Year: 2003..Our current objective is to understand the regiochemical and stereochemical principles that govern the biosynthesis of pharmaceutically useful terpenoids. ..
- PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDERDONALD KUHN; Fiscal Year: 2002....
- Preclinical Evaluation of Bcr/Abl-Directed TyrphostinsScott Kaufmann; Fiscal Year: 2007..abstract_text> ..
- Does FAK mediate implant microtopographyGalen Schneider; Fiscal Year: 2006..This would allow for a controlled, localized, site specific tissue engineering approach in association with Dental implant therapy. ..
- Structural Basis for Isoprenoid BiosynthesisJOSEPH NOEL; Fiscal Year: 2006....
- Pharmacologic modulation of chromatin remodeling in leu*Guido Marcucci; Fiscal Year: 2006..Further, we believe that this schedule is amenable to future combination-based approaches. [unreadable] [unreadable]..
- Alzheimer's Disease Research Center ConferenceLeon Thal; Fiscal Year: 2006..Partial support is requested to defray travel costs of invited speakers and to provide travel awards to minority healthcare providers, junior faculty, postdocs and students. [unreadable] [unreadable] [unreadable]..
- Annual Midwest DNA Repair SymposiumAltaf Wani; Fiscal Year: 2007..unreadable] [unreadable] [unreadable] [unreadable]..
- Molecular Neurobiology of Drug AbuseDONALD KUHN; Fiscal Year: 2006..Kuhn will remain extensively engaged in scientific mentoring activities. ..
- The Urokinase-CD87 System in Macrophage ActivationRobert Sitrin; Fiscal Year: 2004....
- Control of elF4F complex by Vesicular Stomatitis VirusJohn Connor; Fiscal Year: 2007....
- Proposed Role for Neuronal Serotonin N-acetyltransferaseHari Manev; Fiscal Year: 2006..We expect the results to elucidate the role of AANAT/NAS in neuronal functioning, and in the long term, in the pathobiology of depression. ..
- LARG, A Novel Leukemia Associated Guanine Exhange FactorGuido Marcucci; Fiscal Year: 2006..i.). ..
- Enhancing Photodynamic Therapy with COX-2 InhibitionCharles Gomer; Fiscal Year: 2007..If our preliminary findings are confirmed by studies outlined in this proposal, adjunctive COX-2 inhibitor treatment could provide a safe and effective method for improving clinical PDT. [unreadable] [unreadable]..
- 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. ..
- Brain Manganese Deposition in High Risk NeonatesJudy Aschner; Fiscal Year: 2007..unreadable] [unreadable] [unreadable]..
- Airway muscle tone, RhoA & Cytoskeletal remodelingCAROL HIRSHMAN; Fiscal Year: 2007....
- Prostanoids and hypoxic neonatal pulmonary hypertensionCANDICE 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. ..
- Regulation of exocrine cell secretion by Rab proteinsRobert Raffaniello; Fiscal Year: 2006..Therefore, an understanding of the basic mechanisms that regulate exocrine gland secretion is essential. [unreadable] [unreadable]..
- Evaluation of a Biomarker for Acetaminophen ToxicityLaura James; Fiscal Year: 2005..The data generated from this study will lead to enhanced recognition of APAP hepatotoxicity, thus allowing for better identification of "at risk" populations and the creation of prevention strategies. ..
- Chemogenomic Analysis of E. coli Response to NO speciesJames C Liao; Fiscal Year: 2010..If hew TF targets are predicted, then the iteration continues. Otherwise, the predicted networks are verified using genetic and biochemical experiments. ..
- SYNTHESIS OF THE TEDANOLIDES, CYTOTOXIC POLYPROPIONATESMichael Jung; Fiscal Year: 2003....
- Acquisition of FACSVantage SE Flow CytometerYair 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. ..
- Biochemical Effects of Disrupting HSP90Charles Erlichman; Fiscal Year: 2004....
- FLOW SHEAR INDUCED NF-KB MEDIATED REGULATIONSumathy Mohan; Fiscal Year: 2003..Understanding of NF- kappaB signaling mechanisms in VCAM-1 regulation can also be applied to other inflammatory conditions. ..
- Engineering Large scale pathways from organisms to Escherichia coliJames Liao; Fiscal Year: 2008..In particular, selected projects proposed here will be used as modules in a workshop established by FRT at Ohio State and form the basis for a course (Metabolic Engineering) at UCLA. ..
- NOVEL THERAPIES FOR ACETAMINOPHEN TOXICITYLaura James; Fiscal Year: 2004..abstract_text> ..
- Automated Chip-Based Metabolomic AnalysisJames Liao; Fiscal Year: 2006..abstract_text> ..