G Powis

Summary

Affiliation: University of Arizona
Country: USA

Publications

  1. ncbi Thioredoxin redox control of cell growth and death and the effects of inhibitors
    G Powis
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    Chem Biol Interact 111:23-34. 1998
  2. ncbi Hypoxia inducible factor as a cancer drug target
    Sarah J Welsh
    Arizona Cancer Center, 1515 N Campbell Avenue, Tucson, Arizona 85724, USA
    Curr Cancer Drug Targets 3:391-405. 2003
  3. ncbi Hypoxia inducible factor-1alpha as a cancer drug target
    Garth Powis
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    Mol Cancer Ther 3:647-54. 2004
  4. ncbi Properties and biological activities of thioredoxins
    G Powis
    Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724 5024, USA
    Annu Rev Biophys Biomol Struct 30:421-55. 2001
  5. ncbi Properties and biological activities of thioredoxins
    G Powis
    Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724 5024, USA
    Annu Rev Pharmacol Toxicol 41:261-95. 2001
  6. ncbi Selenium and the thioredoxin redox system: effects on cell growth and death
    G Powis
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    Oncol Res 9:303-12. 1997
  7. ncbi The role of the redox protein thioredoxin in cell growth and cancer
    G Powis
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    Free Radic Biol Med 29:312-22. 2000
  8. ncbi In vivo molecular pharmacology and antitumor activity of the targeted Akt inhibitor PX-316
    Emmanuelle J Meuillet
    Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA
    Oncol Res 14:513-27. 2004
  9. ncbi Thioredoxin peroxidase-1 (peroxiredoxin-1) is increased in thioredoxin-1 transfected cells and results in enhanced protection against apoptosis caused by hydrogen peroxide but not by other agents including dexamethasone, etoposide, and doxorubicin
    M I Berggren
    Arizona Cancer Center, University of Arizona, Tucson, Arizona, 85724-5024, USA
    Arch Biochem Biophys 392:103-9. 2001
  10. ncbi Cloning, sequencing and functional expression of a novel human thioredoxin reductase
    P Y Gasdaska
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    FEBS Lett 442:105-11. 1999

Detail Information

Publications63

  1. ncbi Thioredoxin redox control of cell growth and death and the effects of inhibitors
    G Powis
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    Chem Biol Interact 111:23-34. 1998
    ..A class of disulfide inhibitors of thioredoxin has been identified. These disulfides inhibit cancer cell growth in culture and have antitumor activity against some human tumor xenografts in animals...
  2. ncbi Hypoxia inducible factor as a cancer drug target
    Sarah J Welsh
    Arizona Cancer Center, 1515 N Campbell Avenue, Tucson, Arizona 85724, USA
    Curr Cancer Drug Targets 3:391-405. 2003
    ..HIF-1 is therefore an important target for cancer chemotherapy. This review summarizes the literature surrounding the control of HIF-1, its role in cancer and potential drugs to target the pathway for cancer therapy...
  3. ncbi Hypoxia inducible factor-1alpha as a cancer drug target
    Garth Powis
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    Mol Cancer Ther 3:647-54. 2004
    ..Only in this way will it be possible to determine if HIF-1alpha is a valid cancer drug target in humans...
  4. ncbi Properties and biological activities of thioredoxins
    G Powis
    Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724 5024, USA
    Annu Rev Biophys Biomol Struct 30:421-55. 2001
    ..An increased level of thioredoxin-1 is found in many human tumors, where it is associated with aggressive tumor growth. Drugs are being developed that inhibit thioredoxin and that have antitumor activity...
  5. ncbi Properties and biological activities of thioredoxins
    G Powis
    Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724 5024, USA
    Annu Rev Pharmacol Toxicol 41:261-95. 2001
    ..An increased level of thioredoxin-1 is found in many human tumors, where it is associated with aggressive tumor growth. Drugs are being developed that inhibit thioredoxin and that have antitumor activity...
  6. ncbi Selenium and the thioredoxin redox system: effects on cell growth and death
    G Powis
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    Oncol Res 9:303-12. 1997
    ..Several of the compounds inhibited cancer cell colony formation in vitro with IC50s as low as 2 microM...
  7. ncbi The role of the redox protein thioredoxin in cell growth and cancer
    G Powis
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    Free Radic Biol Med 29:312-22. 2000
    ..Because of its role in stimulating cancer cell growth and as an inhibitor of apoptosis, thioredoxin offers a target for the development of drugs to treat and prevent cancer...
  8. ncbi In vivo molecular pharmacology and antitumor activity of the targeted Akt inhibitor PX-316
    Emmanuelle J Meuillet
    Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA
    Oncol Res 14:513-27. 2004
    ..Thus, PX-316 is the lead compound of a new class of potential agents that inhibit Akt survival signaling...
  9. ncbi Thioredoxin peroxidase-1 (peroxiredoxin-1) is increased in thioredoxin-1 transfected cells and results in enhanced protection against apoptosis caused by hydrogen peroxide but not by other agents including dexamethasone, etoposide, and doxorubicin
    M I Berggren
    Arizona Cancer Center, University of Arizona, Tucson, Arizona, 85724-5024, USA
    Arch Biochem Biophys 392:103-9. 2001
    ..The results show that an increase in TrxP-1 expression contributes to the protection against H(2)O(2) induced apoptosis caused by Trx-1, but does not protect against apoptosis induced by other agents...
  10. ncbi Cloning, sequencing and functional expression of a novel human thioredoxin reductase
    P Y Gasdaska
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    FEBS Lett 442:105-11. 1999
    ..Transient transfection of human embryonal kidney cells results in a 5-fold increase in thioredoxin reductase activity but no increase in glutathione reductase activity...
  11. ncbi Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling
    Nathan T Ihle
    Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724-5024, USA
    Mol Cancer Ther 3:763-72. 2004
    ..PX-866 exhibits single agent in vivo antitumor activity and increases the antitumor effects of cisplatin and radiation treatment...
  12. ncbi Alternative splicing is associated with decreased expression of the redox proto-oncogene thioredoxin-1 in human cancers
    M M Berggren
    Arizona Cancer Center, University of Arizona, Tucson 85724-5024, USA
    Arch Biochem Biophys 389:144-9. 2001
    ..The cell lines having the alternatively spliced Trx-1 mRNA had 73% lower total Trx-1 mRNA than the other cell lines, suggesting that alternative splicing may control the level of Trx-1 mRNA in some cancer cells...
  13. ncbi Human thioredoxin homodimers: regulation by pH, role of aspartate 60, and crystal structure of the aspartate 60 --> asparagine mutant
    J F Andersen
    Department of Biochemistry and Arizona Cancer Center, University of Arizona, Tucson, Arizona 85721, USA
    Biochemistry 36:13979-88. 1997
    ..The values obtained for Kapp suggest human thioredoxin may dimerize in vivo and possible roles for such dimers are discussed...
  14. ncbi Increased thioredoxin-1 inhibits SSAT expression in MCF-7 human breast cancer cells
    B Husbeck
    Arizona Cancer Center, University of Arizona, Tucson, AZ 85724 5024, USA
    Biochem Biophys Res Commun 306:469-75. 2003
    ..The results suggest that Trx-1 may play a role in the redox regulation of SSAT expression and polyamine homeostasis that could contribute to the biological effects of Trx-1...
  15. ncbi DNA microarray reveals increased expression of thioredoxin peroxidase in thioredoxin-1 transfected cells and its functional consequences
    B Husbeck
    Arizona Cancer Center, University of Arizona, Tucson 85724-5024, USA
    Adv Exp Med Biol 500:157-68. 2001
    ..Thus, increased thioredoxin peroxidase-2 expression does not explain the widespread antiapoptotic effects of thioredoxin-1...
  16. ncbi Antitumor activity and pharmacodynamic properties of PX-478, an inhibitor of hypoxia-inducible factor-1alpha
    Sarah Welsh
    Arizona Cancer Center, University of Arizona, Tucson, AZ, USA
    Mol Cancer Ther 3:233-44. 2004
    ....
  17. ncbi The thioredoxin-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) decreases vascular permeability in tumor xenografts monitored by dynamic contrast enhanced magnetic resonance imaging
    Benedicte F Jordan
    Department of Biochemistry, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA
    Clin Cancer Res 11:529-36. 2005
    ....
  18. ncbi Stability of phosphoprotein as a biological marker of tumor signaling
    Amanda F Baker
    Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA
    Clin Cancer Res 11:4338-40. 2005
    ..Rapid processing of biopsies is essential and postoperative surgical samples may be of limited value because of the time to fixation...
  19. ncbi The expression of the molecular chaperone calnexin is decreased in cancer cells grown as colonies compared to monolayer
    L C Yeates
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    Biochem Biophys Res Commun 238:66-70. 1997
    ..The results suggest that there is a signal for the up-regulation of calnexin expression when cells contact a substrate which allows cell adhesion...
  20. ncbi Dynamic contrast-enhanced and diffusion MRI show rapid and dramatic changes in tumor microenvironment in response to inhibition of HIF-1alpha using PX-478
    Benedicte F Jordan
    Department of Biochemistry, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA
    Neoplasia 7:475-85. 2005
    ..This is the earliest significant response of ADC to therapy yet reported. Based on these preclinical findings, both of these imaging endpoints will be included in the clinical trial of PX-478...
  21. ncbi The antitumor thioredoxin-1 inhibitor PX-12 (1-methylpropyl 2-imidazolyl disulfide) decreases thioredoxin-1 and VEGF levels in cancer patient plasma
    Amanda F Baker
    Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA
    J Lab Clin Med 147:83-90. 2006
    ..Furthermore, PX-12 decreases plasma VEGF levels that may contribute to the antitumor activity of PX-12...
  22. ncbi Human thioredoxin reductase gene localization to chromosomal position 12q23-q24.1 and mRNA distribution in human tissue
    J R Gasdaska
    Arizona Cancer Center, University of Arizona, Tucson 85724 5024, USA
    Genomics 37:257-9. 1996
    ..1 by in situ hybridization. We have also determined the relative tissue distribution of thioredoxin reductase mRNA as well as thioredoxin mRNA by probing a Northern blot of several human normal tissues...
  23. ncbi Catalase-overexpressing thymocytes are resistant to glucocorticoid-induced apoptosis and exhibit increased net tumor growth
    M E Tome
    Department of Pathology, University of Arizona, Tucson 85724, USA
    Cancer Res 61:2766-73. 2001
    ..These data suggest that: (a) oxidative stress plays a critical role in steroid-induced apoptosis prior to the commitment of the cells to undergo apoptosis; and (b) resistance to oxidative stress can contribute to tumor growth...
  24. ncbi Crystal structures of reduced, oxidized, and mutated human thioredoxins: evidence for a regulatory homodimer
    A Weichsel
    Department of Biochemistry, University of Arizona, Tucson 85721, USA
    Structure 4:735-51. 1996
    ..Human thioredoxin reduces the disulfide bonds of numerous proteins in vitro, and can activate transcription factors such as NFkB in vivo. Thioredoxin can also act as a growth factor, and is overexpressed and secreted in certain tumor cells...
  25. ncbi Thioredoxin-1 binds to the C2 domain of PTEN inhibiting PTEN's lipid phosphatase activity and membrane binding: a mechanism for the functional loss of PTEN's tumor suppressor activity
    Emmanuelle J Meuillet
    Arizona Cancer Center, University of Arizona, 1515 N Campbell Blvd, Tucson, AZ 85724, USA
    Arch Biochem Biophys 429:123-33. 2004
    ..The results of the study suggest that the increased levels of Trx-1 in human tumors could lead to functional inhibition of PTEN tumor suppressor activity providing an additional mechanism for tumorigenesis with loss of PTEN activity...
  26. ncbi The antitumor agent imexon activates antioxidant gene expression: evidence for an oxidative stress response
    Amanda F Baker
    University of Arizona Cancer Center, Tucson, Arizona 85724, USA
    Clin Cancer Res 13:3388-94. 2007
    ..The aim of this study was to identify biomarkers that may be predictive for the clinical activity of the redox-active antitumor agent imexon...
  27. ncbi The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts
    Nathan T Ihle
    Arizona Cancer Center, University of Arizona, Tucson, USA
    Mol Cancer Ther 4:1349-57. 2005
    ..Thus, PX-866, by inhibiting PI3-K signaling, may have clinical use in increasing the response to EGFR inhibitors such as gefitinib in patients with NSCLC and possibly in other cancers who do not respond to EGFR inhibition...
  28. ncbi Identification of thioredoxin-interacting protein 1 as a hypoxia-inducible factor 1alpha-induced gene in pancreatic cancer
    Amanda F Baker
    College of Medicine, Hematology Oncology, Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA
    Pancreas 36:178-86. 2008
    ..To investigate the expression of thioredoxin-interacting protein (TXNIP) during hypoxia and its dependency on hypoxia-inducible factor 1alpha (HIF-1alpha) in pancreatic cancer cell lines...
  29. ncbi The redox protein thioredoxin-1 (Trx-1) increases hypoxia-inducible factor 1alpha protein expression: Trx-1 overexpression results in increased vascular endothelial growth factor production and enhanced tumor angiogenesis
    Sarah J Welsh
    Arizona Cancer Center, University of Arizona, Tucson, Arizona, 85724 5024, USA
    Cancer Res 62:5089-95. 2002
    ..2 cells transfected with Trx-1 showed significantly increased tumor VEGF and angiogenesis. The results suggest that Trx-1 increases HIF-1alpha protein levels in cancer cells and increases VEGF production and tumor angiogenesis...
  30. ncbi The thioredoxin redox inhibitors 1-methylpropyl 2-imidazolyl disulfide and pleurotin inhibit hypoxia-induced factor 1alpha and vascular endothelial growth factor formation
    Sarah J Welsh
    Arizona Cancer Center, Tucson, Arizona 85724, USA
    Mol Cancer Ther 2:235-43. 2003
    ..The results suggest that inhibition of HIF-1alpha by Trx-1 inhibitors may contribute to the growth inhibitory and antitumor activity of these agents...
  31. ncbi Specific inhibition of the Akt1 pleckstrin homology domain by D-3-deoxy-phosphatidyl-myo-inositol analogues
    Emmanuelle J Meuillet
    Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA
    Mol Cancer Ther 2:389-99. 2003
    ..This study shows that the DPIs are a novel class of growth inhibitory agents with a novel mechanism of action through binding to the PH domain of Akt and inhibition of Akt activation...
  32. ncbi The redox protein thioredoxin-1 regulates the constitutive and inducible expression of the estrogen metabolizing cytochromes P450 1B1 and 1A1 in MCF-7 human breast cancer cells
    Bryan Husbeck
    Arizona Cancer Center, University of Arizona, 1515 N. Campbell Avenue, Tucson, AZ 85724-5024, USA
    Carcinogenesis 23:1625-30. 2002
    ..The results suggest that Trx-1 is involved in the constitutive expression of CYP1B1 and is required for the induction of CYP1B1 and CYP1A1 by TCDD in human MCF-7 breast cancer cells...
  33. ncbi Increased expression of mitochondrial peroxiredoxin-3 (thioredoxin peroxidase-2) protects cancer cells against hypoxia and drug-induced hydrogen peroxide-dependent apoptosis
    Larisa Nonn
    Arizona Cancer Center, University of Arizona, Tucson, AZ 85724 5024, USA
    Mol Cancer Res 1:682-9. 2003
    ..Thus, mitochondrial Prdx3 is an important cellular antioxidant that regulates physiological levels of H(2)O(2), leading to decreased cell growth while protecting cells from the apoptosis-inducing effects of high levels of H(2)O(2)...
  34. ncbi Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor
    Emmanuelle J Meuillet
    Departments of Nutritional Sciences and Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, USA
    Mol Cancer Ther 9:706-17. 2010
    ..When given >5 days, PHT-427 caused no weight loss or change in blood chemistry. Thus, we report a novel PH domain binding inhibitor of PDPK1/Akt signaling with significant in vivo antitumor activity and minimal toxicity...
  35. ncbi In vitro and in vivo activity of novel small-molecule inhibitors targeting the pleckstrin homology domain of protein kinase B/AKT
    Sylvestor A Moses
    Department of Molecular and Cellular Biology, The University of Arizona, Tucson, Arizona 85721 0038, USA
    Cancer Res 69:5073-81. 2009
    ..In summary, a pharmacophore for PH domain inhibitors targeting AKT function was developed. Computer-aided modeling, synthesis, and testing produced novel AKT PH domain inhibitors that exhibit promising preclinical properties...
  36. ncbi Discovery of a novel class of AKT pleckstrin homology domain inhibitors
    Daruka Mahadevan
    College of Medicine, Arizona Cancer Center, University of Arizona, Tucson, AZ 85721 0038, USA
    Mol Cancer Ther 7:2621-32. 2008
    ..These results show that these compounds are the first small molecules selectively targeting the PH domain of AKT...
  37. ncbi Increased expression of thioredoxin-1 in human colorectal cancer is associated with decreased patient survival
    Jennifer Raffel
    Department of Pathology, University of Arizona, Tucson, AZ 85724 5024, USA
    J Lab Clin Med 142:46-51. 2003
    ....
  38. ncbi A multisample assay for inhibitors of phosphatidylinositol phospholipase C: identification of naturally occurring peptide inhibitors with antiproliferative activity
    S R Hill
    Arizona Cancer Center, University of Arizona, Tucson 85724
    Anticancer Drug Des 9:353-61. 1994
    ..It is possible that inhibition of PtdInsPLC is responsible for the cell growth inhibition and antitumour properties of the peptide compounds...
  39. ncbi Metabolite changes in HT-29 xenograft tumors following HIF-1alpha inhibition with PX-478 as studied by MR spectroscopy in vivo and ex vivo
    Benedicte F Jordan
    Department of Biochemistry and Molecular Biophysics, Arizona Cancer Center, Tucson, AZ 85724, USA
    NMR Biomed 18:430-9. 2005
    ....
  40. ncbi Cloning and sequencing of a human thioredoxin reductase
    P Y Gasdaska
    Arizona Cancer Center, Tucson 85724, USA
    FEBS Lett 373:5-9. 1995
    ..Human thioredoxin reductase contains the redox-active cysteines in the putative FAD binding domain and has a dimer interface domain not previously seen with prokaryote and lower eukaryote thioredoxin reductases...
  41. ncbi The absence of mitochondrial thioredoxin 2 causes massive apoptosis, exencephaly, and early embryonic lethality in homozygous mice
    Larisa Nonn
    Arizona Cancer Center, University of Arizona, Tucson, Arizona 85714 5024, USA
    Mol Cell Biol 23:916-22. 2003
    ..These results show that the mitochondrial redox protein Trx-2 is required for normal development of the mouse embryo and for actively respiring cells...
  42. ncbi Increased skin carcinogenesis in a keratinocyte directed thioredoxin-1 transgenic mouse
    Debbie Mustacich
    Arizona Cancer Center and Department of Pathology, University of Arizona, Tucson, AZ 85724, USA
    Carcinogenesis 25:1983-9. 2004
    ..Thus, increased thioredoxin-1 in keratinocytes acts as an enhancer of carcinogenesis in the DMBA/TPA two-stage model of skin carcinogenesis in mice...
  43. ncbi The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures
    Amy L Howes
    Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cancer Ther 6:2505-14. 2007
    ..In addition, we propose that the use of three-dimensional tumor models is more predictive of in vivo growth inhibition by PI3K inhibitors in cancer cell lines lacking phosphatase and tensin homologue activity or expression...
  44. ncbi Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha
    Mei Y Koh
    M D Anderson Cancer Center, University of Texas, FC 6 3044, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Mol Cancer Ther 7:90-100. 2008
    ..We conclude that PX-478 inhibits HIF-1alpha at multiple levels that together or individually may contribute to its antitumor activity against HIF-1alpha-expressing tumors...
  45. ncbi Hypoxia: importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy
    James L Tatum
    National Cancer Institute, Executive Plaza North, Room 6000, 6130 Executive Boulevard, Rockville, MD 20852 7440, USA
    Int J Radiat Biol 82:699-757. 2006
    ....
  46. ncbi Practicalities of drugging the phosphatidylinositol-3-kinase/Akt cell survival signaling pathway
    Garth Powis
    M.D. Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 12:2964-6. 2006
  47. ncbi Thioredoxin reductase and cancer cell growth inhibition by organogold(III) compounds
    Lars Engman
    Organic Chemistry, Department of Chemistry, Uppsala University, Uppsala, Sweden
    Anticancer Drugs 17:539-44. 2006
    ..6 micromol/l). Unfortunately, the compound did not show any anti-tumor activity against MCF-7 breast cancer and HT-29 colon cancer xenografts in scid mice...
  48. ncbi Thioredoxin signaling as a target for cancer therapy
    Garth Powis
    Department of Experimental Therapeutics, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 4009, USA
    Curr Opin Pharmacol 7:392-7. 2007
    ..A surrogate target for Trx-1 may be thioredoxin reductase (TR). Drugs that inhibit Trx-1 and TR are in clinical development with early promising results...
  49. ncbi Molecular pharmacology and antitumor activity of palmarumycin-based inhibitors of thioredoxin reductase
    Garth Powis
    Department of Experimental Therapeutics, M D Anderson Cancer Center, FC 6 3044, 1515 Holcombe Boulevard, Houston, TX 77030 4009, USA
    Mol Cancer Ther 5:630-6. 2006
    ..Thus, the study shows that water-soluble inhibitors of thioredoxin reductase-1, such as PX-916, can block thioredoxin-1 signaling in tumors producing marked inhibition of tumor growth...
  50. ncbi Natural product based inhibitors of the thioredoxin-thioredoxin reductase system
    Peter Wipf
    Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Org Biomol Chem 2:1651-8. 2004
    ..Nanomolar inhibitors for the Trx/TrxR redox control system were prepared by this approach and compared to series of natural product isolates. Cytotoxicity in MCF-7 cell assays ranged from an IC50 of 1.6 to >100 microM...
  51. ncbi Vascular endothelial growth factor receptor-1 and receptor-2 initiate a phosphatidylinositide 3-kinase-dependent clonogenic response in acute myeloid leukemia cells
    Alan F List
    The H Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA
    Exp Hematol 32:526-35. 2004
    ..To evaluate receptor-selective trophic response to VEGF-A in AML cells, we investigated receptor-specific ligand activation responsible for VEGF-initiated clonogenic response...
  52. ncbi Synthesis and biological evaluation of synthetic viridins derived from C(20)-heteroalkylation of the steroidal PI-3-kinase inhibitor wortmannin
    Peter Wipf
    Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Org Biomol Chem 2:1911-20. 2004
    ..Among the ten most promising derivatives, six demonstrated lower liver toxicity and greater promise for inhibition of tumor cell growth than the lead structure wortmannin...
  53. ncbi Redox potential of human thioredoxin 1 and identification of a second dithiol/disulfide motif
    Walter H Watson
    Department of Biochemistry, Emory University, Atlanta, Georgia 30322, USA
    J Biol Chem 278:33408-15. 2003
    ....
  54. ncbi Thioredoxin reductase and cancer cell growth inhibition by organotellurium antioxidants
    Lars Engman
    Department of Organic Chemistry, Institute of Chemistry, Uppsala University, Uppsala, Sweden
    Anticancer Drugs 14:153-61. 2003
    ..Whereas antioxidant 1d also inhibited the growth of MCF-7 human breast cancer cells in culture at a similar level (IC50 = 1.8 microM), the other TrxR inhibitors were inactive in concentrations below about 10 M...
  55. ncbi Proceedings of the Oxygen Homeostasis/Hypoxia Meeting
    Bennett Kaufman
    TRI Inc, Rockville, Maryland, USA
    Cancer Res 64:3350-6. 2004
  56. ncbi Synthesis and biological activity of prodrug inhibitors of the thioredoxin-thioredoxin reductase system
    Peter Wipf
    Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Org Biomol Chem 3:3880-2. 2005
    ..A series of palmarumycin prodrugs and water-soluble analogs has been synthesized and assayed for inhibition of the thioredoxin-thioredoxin reductase system. Increased aqueous solubility led to an improved in vivo activity profile...
  57. ncbi Cyclodextrin-derived diorganyl tellurides as glutathione peroxidase mimics and inhibitors of thioredoxin reductase and cancer cell growth
    Michael McNaughton
    Department of Organic Chemistry, Institute of Chemistry, Uppsala University, Box 599, S-751 24 Uppsala, Sweden
    J Med Chem 47:233-9. 2004
    ..Two of the compounds (4c and 5) were found to inhibit the growth of MCF-7 cells in culture with IC(50) values in the low micromolar range...
  58. ncbi The skin and hair as surrogate tissues for measuring the target effect of inhibitors of phosphoinositide-3-kinase signaling
    Ryan Williams
    M.D. Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Chemother Pharmacol 58:444-50. 2006
    ..CONCLUSIONS: Hair offers a way of measuring the effects of PI-3-K signaling inhibitors and, in cancer patients, may provide a readily obtainable surrogate tissue for assessing PI-3-K and phospho-Akt inhibition in tumor...
  59. ncbi OSU-03012 promotes caspase-independent but PERK-, cathepsin B-, BID-, and AIF-dependent killing of transformed cells
    Adly Yacoub
    Department of Biochemistry, Massey Cancer Center Virginia Commonwealth University, Richmond, VA 23298-0058, USA
    Mol Pharmacol 70:589-603. 2006
    ....
  60. ncbi Achieving personalized cancer medicine: trials and tribulations
    Garth Powis
    Department of Experimental Therapeutics, M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA
    J Investig Med 54:235-7. 2006
  61. ncbi The hypoxic inducible stress response as a target for cancer drug discovery
    Sarah J Welsh
    Oxford Medical School, University of Oxford, Oxford, UK
    Semin Oncol 33:486-97. 2006
    ..The challenges will be to determine whether the effects of these agents that are seen is due to HIF-1 inhibition and to identify which patients are most likely to benefit from treatment with HIF-1 inhibitors...
  62. ncbi Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer
    Yanan Yang
    Department of Thoracic Head and Neck Medical Oncology, University of Texas M D Anderson Cancer Center, Houston, Texas, United States of America
    PLoS ONE 3:e2220. 2008
    ..The signals activated by oncogenic K-ras that mediate BASC expansion have not been fully defined...
  63. ncbi Thioredoxin reductase and cancer cell growth inhibition by organotellurium compounds that could be selectively incorporated into tumor cells
    Lars Engman
    Department of Organic Chemistry, Institute of Chemistry, Uppsala University, PO Box 599, S 751 24, Uppsala, Sweden
    Bioorg Med Chem 11:5091-100. 2003
    ....