- AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity
Christine M Chresta
AstraZeneca, Cheshire, United Kingdom
Cancer Res 70:288-98. 2010
..Notably, AZD8055 results in significant growth inhibition and/or regression in xenografts, representing a broad range of human tumor types. AZD8055 is currently in phase I clinical trials...
- Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt
L del Peso
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Science 278:687-9. 1997
..Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway...
- Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation
Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20889, USA
Cancer Res 61:3986-97. 2001
- Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)
Juan M García-Martínez
MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK
Biochem J 421:29-42. 2009
..Our results indicate that Ku-0063794 will be useful in delineating the physiological roles of mTOR and may have utility in treatment of cancers in which this pathway is inappropriately activated...
- Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty
Bengt I Eriksson
Sahlgrenska University Hospital Ostra, Gothenburg, Sweden
N Engl J Med 358:2765-75. 2008
..This phase 3 trial compared the efficacy and safety of rivaroxaban, an oral direct inhibitor of factor Xa, with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty...
- Effective targeted gene 'knockdown' in zebrafish
Arnold and Mabel Beckman Center for Transposon Research at the University of Minnesota, Department of Genetics, Cell Biology and Development, Minneapolis, Minnesota, USA
Nat Genet 26:216-20. 2000
..Conserved vertebrate processes and diseases are now amenable to a systematic, in vivo, reverse-genetic paradigm using zebrafish embryos...
- Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty
Michael R Lassen
Nordsjaellands Hospital, Hørsholm, Denmark
N Engl J Med 358:2776-86. 2008
..We investigated the efficacy of rivaroxaban, an orally active direct factor Xa inhibitor, in preventing venous thrombosis after total knee arthroplasty...
- Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial
Alexander G G Turpie
McMaster University, Hamilton, Ontario L8L 2X2, Canada
Lancet 373:1673-80. 2009
..We aimed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty...
- Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide
Department of Pharmacology, National University of Singapore, Singapore
Circulation 117:2351-60. 2008
- Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial
Ajay K Kakkar
Barts and the London School of Medicine and Dentistry, London, UK
Lancet 372:31-9. 2008
..Our aim was to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin...
- Exploring the specificity of the PI3K family inhibitor LY294002
Severine I Gharbi
Ludwig Institute for Cancer Research, Proteomics Unit, Cruciform Building, Gower Street, London WCE1 6BT, UK
Biochem J 404:15-21. 2007
..The present study reveals that LY294002 not only binds to class I PI3Ks and other PI3K-related kinases, but also to novel targets seemingly unrelated to the PI3K family...
- Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM
KuDOS Pharmaceuticals Ltd, Cambridge Science Park, Milton Road, Cambridge, UK
Cancer Res 64:9152-9. 2004
..We conclude that KU-55933 is a novel, specific, and potent inhibitor of the ATM kinase...
- Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor
Bayer HealthCare AG, Institute of Clinical Pharmocology, D 42096 Wuppertal, Germany
Clin Pharmacol Ther 78:412-21. 2005
..The aim of this study was to investigate the safety, pharmacodynamics, and pharmacokinetics of BAY 59--7939, an oral, direct factor Xa inhibitor...
- Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide
R A Ross
Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, AB25 2ZD, Scotland, Aberdeen, UK
Eur J Pharmacol 401:121-30. 2000
..In contrast, the inhibition by palmitoylethanolamide does not appear to be mediated by cannabinoid receptors...
- Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939--an oral, direct Factor Xa inhibitor--after multiple dosing in healthy male subjects
Institute of Clinical Pharmacology, Bayer HealthCare AG, 42096 Wuppertal, Germany
Eur J Clin Pharmacol 61:873-80. 2005
- Phosphatidylinositol-3-kinase as a therapeutic target in melanoma
Saadia A Aziz
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
Clin Cancer Res 15:3029-36. 2009
..We assessed expression of PI3K in melanomas and nevi, and studied associations between PI3K pathway members and in vitro response to a PI3K inhibitor, LY294002...
- Inhibition of phosphatidylinositol 3'-kinase increases efficacy of paclitaxel in in vitro and in vivo ovarian cancer models
Center for Reproductive Sciences, University of California, San Francisco, San Francisco, California 94143 0556, USA
Cancer Res 62:1087-92. 2002
..Our data suggest that a combination of a PI3k inhibitor and conventional chemotherapy may provide an effective approach to inhibiting tumor growth and ascites production in ovarian cancer with acceptable side effects...
- Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects
Clinical Pharmacology, Bayer HealthCare AG, D 42096 Wuppertal, Germany
Curr Med Res Opin 24:2757-65. 2008
..The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of rivaroxaban--a novel, oral, direct Factor Xa (FXa) inhibitor--in healthy elderly subjects...
- Hydrogen sulfide inhibits proliferation and release of IL-8 from human airway smooth muscle cells
Mark M Perry
Experimental Studies, National Heart and Lung Institute, Imperial College London, London, United Kingdom
Am J Respir Cell Mol Biol 45:746-52. 2011
..Therefore, regulation of H(2)S may represent a novel approach to controlling ASM proliferation and cytokine release that is found in patients with asthma...
- Phosphatidylinositol 3-kinase inhibitor(LY294002) induces apoptosis of human nasopharyngeal carcinoma in vitro and in vivo
Department of Pathology, School of Medicine, Shandong University, 250012 Jinan, China
J Exp Clin Cancer Res 29:34. 2010
..To evaluate whether PI3K/Akt pathway could effect on apoptosis and its mechanism in nasopharyngeal carcinoma cells...
- G1 cell cycle progression and the expression of G1 cyclins are regulated by PI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells
1820 MBR Cancer Center and Dept of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 9300, USA
Am J Physiol Cell Physiol 287:C281-91. 2004
..These results indicate that PI3K mediates G(1) progression and cyclin expression through activation of an AKT/mTOR/p70S6K1 signaling pathway in the ovarian cancer cells...
- Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion
Sarah E Golding
Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA 23298 0058, USA
Mol Cancer Ther 8:2894-902. 2009
..Altogether, KU-60019 inhibits the DNA damage response, reduces AKT phosphorylation and prosurvival signaling, inhibits migration and invasion, and effectively radiosensitizes human glioma cells...
- Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum
Anatol C Kreitzer
Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA
Neuron 34:787-96. 2002
..Because interneurons can project over several hundred micrometers, this inhibition of firing allows cells to regulate synaptic inputs at distances well beyond the limits of endocannabinoid diffusion...
- Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa inhibitor
Meyer Michel Samama
Hotel Dieu University Hospital, Paris, France 2Biomnis Laboratory, Ivry sur Seine, France
Thromb Haemost 103:815-25. 2010
..Finally, all clotting and chromogenic assays showed a concentration-dependent effect induced by rivaroxaban...
- The effect of hydrogen sulfide donors on lipopolysaccharide-induced formation of inflammatory mediators in macrophages
Peninsula Medical School, University of Exeter, St Luke s Campus, Exeter, Devon, England
Antioxid Redox Signal 12:1147-54. 2010
..This study may also explain some of the apparent discrepancies in the literature regarding the pro- versus antiinflammatory role of H(2)S...
- Population pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor Xa inhibitor--in patients undergoing major orthopaedic surgery
Clinical Pharmacology, Bayer HealthCare AG, Aprather Weg 18a, Wuppertal, Germany
Clin Pharmacokinet 47:203-16. 2008
- The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation
Wen Jie Cai
Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China
Cardiovasc Res 76:29-40. 2007
..Hydrogen sulfide (H(2)S) has been reported to be a gasotransmitter which regulates cardiovascular homeostasis. The present study aims to examine the hypothesis that hydrogen sulfide is able to promote angiogenesis...
- Akt inhibitor A-443654 induces rapid Akt Ser-473 phosphorylation independent of mTORC1 inhibition
E K H Han
Abbott Laboratories, Global Pharmaceutical Research Division, Cancer Research, IL 60064, USA
Oncogene 26:5655-61. 2007
- ER-alpha36, a variant of ER-alpha, promotes tamoxifen agonist action in endometrial cancer cells via the MAPK/ERK and PI3K/Akt pathways
Sheng Li Lin
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences and Graduate School, Chinese Academy of Sciences, Beijing, China
PLoS ONE 5:e9013. 2010
..ER-alpha36 lacks intrinsic transcription activity and mainly mediates nongenomic estrogen signaling. Here, we studied the role of nongenomic estrogen signaling pathways mediated by ER-alpha36 in tamoxifen resistance and agonist action...
- Activation of Akt/GSK-3beta signaling pathway is involved in intermedin(1-53) protection against myocardial apoptosis induced by ischemia/reperfusion
Jun Qiu Song
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
Apoptosis 14:1299-307. 2009
..In conclusion, IMD(1-53) exerts cardioprotective effect against myocardial I/R injury through the activation of the Akt/GSK-3beta signaling pathway to inhibit mitochondria-mediated myocardial apoptosis...
- Bidirectional regulation of mu-opioid and CB1-cannabinoid receptor in rats self-administering heroin or WIN 55,212-2
Institute of Neuroscience, National Research Council CNR, Section of Cagliari, Italy
Eur J Neurosci 25:2191-200. 2007
- Simultaneous inhibition of mTORC1 and mTORC2 by mTOR kinase inhibitor AZD8055 induces autophagy and cell death in cancer cells
AstraZeneca Cancer and Infection Research Area, Alderley Park, UK
Autophagy 6:553-4. 2010
..pAKT also phosphorylates PRAS40, releasing it from the mTORC1 complex, increasing its kinase activity. Finally, AKT regulates FOXO3 phosphorylation, sequestering it in the cytosol in an inactive state...
- Glioblastoma: synergy of growth promotion between CCL5 and NK-1R can be thwarted by blocking CCL5 with miraviroc, an FDA approved anti-HIV drug and blocking NK-1R with aprepitant, an FDA approved anti-nausea drug
R E Kast
Department of Psychiatry, University of Vermont, Burlington, VT 05401, USA
J Clin Pharm Ther 35:657-63. 2010
..The anti-HIV drug, maraviroc, inhibits human CCR5's ligand from binding, and hence blocks CCR5 stimulation. The anti-nausea drug aprepitant blocks substance P signaling at NK-1R...
- Morpholino antisense oligomers: the case for an RNase H-independent structural type
Gene Tools, Corvallis, OR 97339, USA
Biochim Biophys Acta 1489:141-58. 1999
- Chlorambucil cytotoxicity in malignant B lymphocytes is synergistically increased by 2-(morpholin-4-yl)-benzo[h]chomen-4-one (NU7026)-mediated inhibition of DNA double-strand break repair via inhibition of DNA-dependent protein kinase
Montreal Centre for Experimental Therapeutics in Cancer Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada
J Pharmacol Exp Ther 321:848-55. 2007
- A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia
School of Cell and Molecular Biosciences, University of Newcastle upon Tyne Medical School, Newcastle upon Tyne NE2 4HH, United Kingdom
Blood 103:4659-65. 2004
..A concentration-dependent increase in etoposide-induced DSB levels was increased by NU7026. The mechanism of NU7026 potentiation of topo II poisons involves inhibition of NHEJ and a G2/M checkpoint arrest...
- Targeting glucosylceramide synthase sensitizes imatinib-resistant chronic myeloid leukemia cells via endogenous ceramide accumulation
Department of Molecular Biology and Genetics, Izmir Institute of Technology, Faculty of Science, Gulbahce Campus, 35430, Urla, Izmir, Turkey
J Cancer Res Clin Oncol 137:1535-44. 2011
..2 and K562/IMA-1 human CML cells, which exhibit about 2.3- and 19-fold imatinib resistance, respectively...
- Two distinct classes of muscarinic action on hippocampal inhibitory synapses: M2-mediated direct suppression and M1/M3-mediated indirect suppression through endocannabinoid signalling
Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, 13 1 Takara machi, Kanazawa 920 8640, Japan
Eur J Neurosci 19:2682-92. 2004
..Thus, the muscarinic system can influence hippocampal functions by controlling different subsets of inhibitory synapses through the two distinct mechanisms...
- Further characterisation of the cellular activity of the DNA-PK inhibitor, NU7441, reveals potential cross-talk with homologous recombination
Northern Institute for Cancer Research, School of Medical Sciences, Newcastle University, Paul O Gorman Building, Framlington Place, NE2 4HH Newcastle upon Tyne, UK
Cancer Chemother Pharmacol 69:155-64. 2012
..One promising target is DNA-PK, a pivotal kinase in double-strand break repair. The purpose of this study was to further characterise the activity of the DNA-PK inhibitor NU7441, giving some new insights into the biology of DNA-PK...
- Dynamic and reversible restructuring of the ER induced by PDMP in cultured cells
Consiglio Nazionale delle Ricerche Institute of Neuroscience and Department of Medical Pharmacology, Via Vanvitelli 32, University of Milano, 20129 Milano, Italy
J Cell Sci 119:3249-60. 2006
..Our results demonstrate a dynamic relationship between smooth and rough ER and have implications for the mechanisms regulating ER architecture...
- Molecular characterization of a peripheral receptor for cannabinoids
MRC Laboratory of Molecular Biology, Cambridge, UK
Nature 365:61-5. 1993
..Here we report the cloning of a receptor for cannabinoids that is not expressed in the brain but rather in macrophages in the marginal zone of spleen...
- Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: a systematic review
Lucas Vieira dos Santos
Medical Oncology Department, Gastrointestinal Oncology Division, Barretos Cancer Hospital, 520 Brasil St, Barretos, Sao Paulo 14784 011, Brazil
J Natl Cancer Inst 104:1280-92. 2012
..We sought to systematically review the overall impact of NK1R antagonists on CINV prevention...
- Effects of the oral, direct factor xa inhibitor rivaroxaban on platelet-induced thrombin generation and prothrombinase activity
Pharmazentrum frankfurt ZAFES, Institute of Clinical Pharmacology, University Hospital, Frankfurt Main, Theodor Stern Kai 7, D 60590 Frankfurt am Main, Germany
J Clin Pharmacol 47:1398-407. 2007
..Rivaroxaban strongly inhibits platelet-induced thrombin generation, after activation of either platelets or the coagulation pathway, even in the presence of minimal factor Xa inhibition in plasma...
- Safety and efficacy of a bolus injection of landiolol hydrochloride as a premedication for multidetector-row computed tomography coronary angiography
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Circ J 77:146-52. 2013
- Salmonella transforms follicle-associated epithelial cells into M cells to promote intestinal invasion
The Roslin Institute and Royal School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK
Cell Host Microbe 12:645-56. 2012
..Thus, via the activity of a single secreted effector, S. Typhimurium transforms primed epithelial cells into M cells to promote host colonization and invasion...
- Cannabinoids prevent lipopolysaccharide-induced neurodegeneration in the rat substantia nigra in vivo through inhibition of microglial activation and NADPH oxidase
Eun Sook Chung
Department of Biochemistry and Molecular Biology, School of Medicine Kyung Hee University, Seoul 130 701, Korea
Brain Res 1451:110-6. 2012
..The present data suggest that cannabinoids may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with microglial activation...
- Posttraining activation of CB1 cannabinoid receptors in the CA1 region of the dorsal hippocampus impairs object recognition long-term memory
Julia R Clarke
Centro de Memoria, Instituto de Pesquisas Biomédicas, Pontificia Universidade Catolica do Rio Grande do Sul, Av Ipiranga 6690, RS 90610 000 Porto Alegre, Brazil
Neurobiol Learn Mem 90:374-81. 2008
..Our data indicate that activation of hippocampal CB1 receptors early after training hampers consolidation of object recognition memory...
- In smooth muscle, FK506-binding protein modulates IP3 receptor-evoked Ca2+ release by mTOR and calcineurin
Institute of Biomedical and Life Sciences, Neuroscience and Biomedical Systems, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, UK
J Cell Sci 118:5443-51. 2005
..However, FKBP12 might indirectly modulate Ca2+ release through two effector proteins: (1) mTOR, which potentiates and (2) calcineurin, which inhibits Ca2+ release from IP3R in smooth muscle...
- Cannabinoids attenuate the effects of aging upon neuroinflammation and neurogenesis
Department of Psychology, The Ohio State University, Columbus, 43210, USA
Neurobiol Dis 34:300-7. 2009
..Our results provide insight into the role of the endocannabinoid and vanilloid systems upon two different and detrimental aspects of normal and pathological aging, chronic neuroinflammation and decline in neurogenesis...
- Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF
Graeme J Hankey
Stroke Unit, Department of Neurology, Royal Perth Hospital, Perth, Australia
Lancet Neurol 11:315-22. 2012
..We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA)...
- Cost-effectiveness of rivaroxaban compared to warfarin for stroke prevention in atrial fibrillation
University of Connecticut School of Pharmacy, Storrs, CT, USA
Am J Cardiol 110:845-51. 2012
..In conclusion, this Markov model suggests that rivaroxaban therapy may be a cost-effective alternative to adjusted-dose warfarin for stroke prevention in AF...
- Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells
Amy S Clark
Cancer Therapeutics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20889, USA
Mol Cancer Ther 1:707-17. 2002
- Dabigatran and rivaroxaban for prevention of venous thromboembolism--systematic review and adjusted indirect comparison
Y K Loke
School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, UK
J Clin Pharm Ther 36:111-24. 2011
..Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta-analysis, and adjusted indirect comparison...
- Involvement of PI3K/Akt signaling in PTTH-stimulated ecdysteroidogenesis by prothoracic glands of the silkworm, Bombyx mori
Shi Hong Gu
Department of Zoology, National Museum of Natural Science, 1 Kuan Chien Road, Taichung 404, Taiwan, ROC
Insect Biochem Mol Biol 41:197-202. 2011
..mori prothoracic glands between insulin and PTTH signaling, which may play a critical role in precisely regulated ecdysteroidogenesis during development...
- Opposing actions of chronic Delta9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation
Alexander F Hoffman
United States Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Cellular Neurobiology Branch, Electrophysiology Research Unit, Baltimore, Maryland 21224, USA
Learn Mem 14:63-74. 2007
..These data define consequences of repeated Delta(9)-THC exposure for synaptic plasticity in the hippocampus that may help explain memory impairments in humans following chronic marijuana use...
- Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441
Northern Institute for Cancer Research, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
Cancer Res 66:5354-62. 2006
..In conclusion, NU7441 shows sufficient proof of principle through in vitro and in vivo chemosensitization and radiosensitization to justify further development of DNA-PK inhibitors for clinical use...
- t-DARPP regulates phosphatidylinositol-3-kinase-dependent cell growth in breast cancer
Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
Mol Cancer 9:240. 2010
..In this study, we evaluated expression of t-DARPP in human primary breast tumors, and investigated the role of t-DARPP in regulating growth and proliferation in breast cancer cells...
- Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials
German Cancer Society, Berlin, Germany
BMJ 341:c4737. 2010
..To assess the benefits and harms of reboxetine versus placebo or selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression, and to measure the impact of potential publication bias in trials of reboxetine...
- Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer
Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA
Mol Cancer Ther 8:3117-29. 2009
..These results indicate that CB1 and CB2 receptors could be used to develop novel therapeutic strategies against breast cancer growth and metastasis...
- Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002
Anjali K Gupta
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA
Int J Radiat Oncol Biol Phys 56:846-53. 2003
..Inhibition of PI3K by LY294002 can synergistically enhance radiation efficacy. This acts as a proof of principle that inhibition of the Ras to PI3K pathway could be useful clinically...
- The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo
Zheng Wei Lee
Department of Biochemistry, National University of Singapore, Singapore, Singapore
PLoS ONE 6:e21077. 2011
..We also propose that a combination of apoptosis and cell cycle arrest contributes to this effect and that H₂S donors should be investigated further as potential anti-cancer agents...
- Mutant PIK3CA promotes cell growth and invasion of human cancer cells
The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, The Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA
Cancer Cell 7:561-73. 2005
..Treatment with the PI3K inhibitor LY294002 abrogated PIK3CA signaling and preferentially inhibited growth of PIK3CA mutant cells. These data have important implications for therapy of cancers harboring PIK3CA alterations...
- Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells
Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 279:1304-9. 2004
..These data indicate that adiponectin can function to stimulate the new blood vessel growth by promoting cross-talk between AMP-activated protein kinase and Akt signaling within endothelial cells...
- Suppression of HIV-1 infection by a small molecule inhibitor of the ATM kinase
KuDOS Pharmaceuticals Limited, 327 Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK
Nat Cell Biol 7:493-500. 2005
..Consistent with these observations, we demonstrate that a novel and specific small molecule inhibitor of ATM kinase activity, KU-55933, is capable of suppressing the replication of both wild-type and drug-resistant HIV-1...
- Electrophysiologic, cardiohemodynamic and beta-blocking actions of a new ultra-short-acting beta-blocker, ONO-1101, assessed by the in vivo canine model in comparison with esmolol
Department of Pharmacology, Yamanashi Medical University, Japan
J Cardiovasc Pharmacol 34:70-7. 1999
..These results suggest that the suppressive effects of ONO-1101 on cardiovascular performance are significantly less potent than those of esmolol at equipotent beta-blocking doses...
- GYY4137, a novel hydrogen sulfide-releasing molecule, protects against endotoxic shock in the rat
Pharmaceutical Science Research Division, King s College, University of London, London, UK
Free Radic Biol Med 47:103-13. 2009
..These results suggest an anti-inflammatory effect of GYY4137. The possibility that GYY4137 and other slow-releasing H(2)S donors exert anti-inflammatory activity in other models of inflammation and in humans warrants further study...
- Loss in oxidative stress tolerance with aging linked to reduced extracellular signal-regulated kinase and Akt kinase activities
Laboratory of Cellular and Molecular Biology, National Institute on Aging IRP, Baltimore, Maryland 21224, USA
FASEB J 16:114-6. 2002
..Strategies aimed at boosting these host responses to acute oxidant injury could have significant anti-aging benefits...
- Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment
Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford OX3 7JX, United Kingdom
Biol Psychiatry 67:439-45. 2010
..There are few studies of the effect of SSRIs on neural reward mechanisms in humans...
- Cytoprotective effect of glucosylceramide synthase inhibition against daunorubicin-induced apoptosis in human leukemic cell lines
INSERM U563 Centre de Physiopathologie Toulouse Purpan, Institut Claudius Regaud, Toulouse 31052, France
J Biol Chem 279:18256-61. 2004
..In conclusion, this study suggests that sphingomyelin-derived CER in itself is not a second messenger but rather a precursor of both an apoptosis second messenger (GD3) and an apoptosis "protector" (GalCER)...
- LY294002 and LY303511 sensitize tumor cells to drug-induced apoptosis via intracellular hydrogen peroxide production independent of the phosphoinositide 3-kinase-Akt pathway
Tze Wei Poh
Department of Physiology, National University Medical Institute, Faculty of Medicine, National University of Singapore, Singapore, Singapore
Cancer Res 65:6264-74. 2005
- Chronic systemic therapy with low-dose morpholino oligomers ameliorates the pathology and normalizes locomotor behavior in mdx mice
School of Biological Sciences, Royal Holloway, University of London, Surrey, UK
Mol Ther 19:345-54. 2011
- Interactive competition between homologous recombination and non-homologous end joining
Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA
Mol Cancer Res 1:913-20. 2003
..By blocking the two major DSB repair pathways, DNA-PKcs inhibitors should radiosensitize at all cell-cycle stages and are therefore excellent candidates for augmenting cancer radiotherapy...
- Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay
Yu Chen Barrett
Bristol Myers Squibb, Princeton, New Jersey, USA
Thromb Haemost 104:1263-71. 2010
..88-0.89) compared with PT/INR (r2 = 0.36) in patients undergoing VTE treatment suggested that anti-Xa activity was the better indicator of apixaban plasma concentrations...
- The cannabinoid CB1 receptor mediates retrograde signals for depolarization-induced suppression of inhibition in cerebellar Purkinje cells
Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, Kanazawa 920 8640, Japan
J Neurosci 22:1690-7. 2002
..These results clearly indicate that the CB1 receptor mediates retrograde signal for DSI in cerebellar Purkinje cells...
- Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells
Anna Morena D'Alise
CEINGE, Biotecnologie Avanzate, Via Comunale Margherita 482, 80131 Naples, Italy
Mol Cancer Ther 7:1140-9. 2008
..Thus, although our studies raise serious doubts on the application of reversine in regenerative medicine, they support the paradigm that reversine might be a useful agent in cancer chemotherapy...
- Synchronous activation of ERK and phosphatidylinositol 3-kinase pathways is required for collagen and extracellular matrix production in keloids
Ivor J Lim
Departments of Surgery and Orthopaedic Surgery, National University of Singapore, 5, Lower Kent Ridge Road, Singapore 119074
J Biol Chem 278:40851-8. 2003
..These pathways additionally appear to affect the side chain attachments of fibronectin. Modulation of these pathways may suggest a direction for keloid therapy...
- In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939--an oral, direct Factor Xa inhibitor
Cardiovascular Research, Bayer HealthCare AG, Wuppertal, Germany
J Thromb Haemost 3:514-21. 2005
..Bleeding times in rats and rabbits were not significantly affected at antithrombotic doses (3 mg kg(-1) p.o., AV shunt). Based on these results, BAY 59-7939 was selected for clinical development...
- Effective rescue of dystrophin improves cardiac function in dystrophin-deficient mice by a modified morpholino oligomer
McColl Lockwood Laboratory for Muscular Dystrophy, Neuromuscular ALS Center, Carolinas Medical Center, Charlotte, NC 28231, USA
Proc Natl Acad Sci U S A 105:14814-9. 2008
..The high degree of potency of the oligomer in targeting all muscles and the lack of detectable toxicity and immune response support the feasibility of testing the novel oligomer in treating Duchenne muscular dystrophy patients...
- Effect of food, an antacid, and the H2 antagonist ranitidine on the absorption of BAY 59-7939 (rivaroxaban), an oral, direct factor Xa inhibitor, in healthy subjects
Institute of Clinical Pharmacology, Bayer HealthCare AG, Wuppertal, Germany
J Clin Pharmacol 46:549-58. 2006
..Time to maximum PT prolongation was delayed by 0.5 to 1.5 hours after food, with no relevant influence of food type. No significant difference in C(max) and AUC was observed with coadministration of BAY 59-7939 and ranitidine or antacid...
- Body weight has limited influence on the safety, tolerability, pharmacokinetics, or pharmacodynamics of rivaroxaban (BAY 59-7939) in healthy subjects
Clinical Pharmacology, Bayer HealthCare AG, Building 429, Aprather Weg 18a, Wuppertal, D 42096, Germany
J Clin Pharmacol 47:218-26. 2007
..The area under the curve was unaffected by body weight or gender. No other clinically relevant differences were observed, suggesting that rivaroxaban is unlikely to require dose adjustment for body weight or gender...
- Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase
Toxicology Program, Department of Environmental Health, the Graduate Program in Neurobiology and Behavior, The Graduate Program in Molecular and Cell Biology, University of Washington, Seattle, Washington 98195 7234, USA
J Biol Chem 274:22569-80. 1999
..Furthermore, the relative contribution of the ERK and PI 3-kinase pathways to neuronal survival may depend on the type of cellular injury...
- FOXO3a is activated in response to hypoxic stress and inhibits HIF1-induced apoptosis via regulation of CITED2
Walbert J Bakker
Campbell Family Institute for Breast Cancer Research, University Health Network, Ontario Cancer Institute and Princess Margaret Hospital, Toronto, ON M5G 2C1, Canada
Mol Cell 28:941-53. 2007
..Thus, by fine-tuning HIF1 activity, FOXO3a plays an important role in the survival response of normal and cancer cells in response to hypoxic stress...
- Population model of the pharmacokinetics and pharmacodynamics of rivaroxaban--an oral, direct factor xa inhibitor--in healthy subjects
Clinical Pharmacology, Pharmacometry, Bayer HealthCare AG, Wuppertal, Germany
Int J Clin Pharmacol Ther 45:335-44. 2007
..This analysis aimed to define population models for the pharmacokinetics (PK) and pharmacodynamics (PD) ofrivaroxaban in healthy males...
- Cardioprotection induced by hydrogen sulfide preconditioning involves activation of ERK and PI3K/Akt pathways
Cardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Pflugers Arch 455:607-16. 2008
..In conclusion, K(ATP)/PKC/ERK1/2 and PI3K/Akt pathways contributed to SP-induced cardioprotection...
- Population pharmacokinetics and pharmacodynamics of once- and twice-daily rivaroxaban for the prevention of venous thromboembolism in patients undergoing total hip replacement
Bayer HealthCare AG, Aprather Weg 18a, Wuppertal, Germany
Thromb Haemost 100:453-61. 2008
- Effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor, on DNA-dependent protein kinase
Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
Biol Pharm Bull 32:297-300. 2009
..These results indicated that ZSTK474 was the most specific agent among these PI3K inhibitors...
- Inhibition of the phosphatidylinositol 3-kinase/p70(S6)-kinase pathway induces B16 melanoma cell differentiation
INSERM U385, Faculte de Medecine, 06107 Nice, Cedex 02, France
J Biol Chem 271:31824-30. 1996
..Furthermore, we provide evidence which suggests that cAMP-induced melanogenesis and dendricity are, at least partially, mediated by the cAMP inhibition of the phosphatidylinositol 3-kinase/p70(S6)-kinase signaling pathway...
- Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement
B I Eriksson
Sahlgrenska University HospitalOstra, Gothenburg, Sweden
J Thromb Haemost 4:121-8. 2006
..Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants...
- Critical role for PI 3-kinase in the control of erythropoietin-induced erythroid progenitor proliferation
Departement d Hematologie, Institut Cochin, Institut National de la Sante et de la Recherche Medicale U567, Centre National de la Recherche Scientifique, UMR 8104, Universite Rene Descartes, Paris, France
Blood 101:3436-43. 2003
- Potent dual inhibitors of TORC1 and TORC2 complexes (KU-0063794 and KU-0068650) demonstrate in vitro and ex vivo anti-keloid scar activity
Plastic and Reconstructive Surgery Research, Manchester Institute of Biotechnology, University of Manchester, Manchester, UK
J Invest Dermatol 133:1340-50. 2013
..In contrast, Rapamycin induced minimal antitumor activity. In conclusion, potent dual mTORC1 and mTORC2 inhibitors display therapeutic potential for the treatment of KD...
- Role of phosphoinositide 3-kinase in activation of ras and mitogen-activated protein kinase by epidermal growth factor
Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom
Mol Cell Biol 19:4279-88. 1999
- Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism
A C Gingras
Department of Biochemistry and McGill Cancer Center, McGill University, Montreal, Quebec, H3G 1Y6, Canada
Genes Dev 13:1422-37. 1999
..Taken together, our results suggest that 4E-BP1 phosphorylation by FRAP/mTOR on Thr-37 and Thr-46 is a priming event for subsequent phosphorylation of the carboxy-terminal serum-sensitive sites...
- Roles of ceramide synthase and ceramide clearence genes in nilotinib-induced cell death in chronic myeloid leukemia cells
Department of Molecular Biology and Genetics, Faculty of Science, Izmir Institute of Technology, Urla, Izmir, Turkey
Leuk Lymphoma 52:1574-84. 2011
..On the other hand, manipulating bioactive sphingolipids toward generation/accumulation of ceramides increased the apoptotic effects of nilotinib in CML cells...
- Safety evaluation of aprepitant for the prevention of chemotherapy-induced nausea and vomiting
Christina H Ruhlmann
Odense University Hospital, Department of Oncology, Sdr Boulevard 29, DK 5000 Odense C, Denmark
Expert Opin Drug Saf 10:449-62. 2011
..Aprepitant is co-administered with a 5-HT(3) RA and a corticosteroid. Although aprepitant is safe, in most clinical settings potential drug-drug interactions need to be considered before prescription...
- Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE
University of Vermont, Dept of Medicine, Fletcher Allen Health Care, 89 Beaumont Ave, Given Bldg E 214, Burlington, VT 05405, USA
J Clin Oncol 29:1495-501. 2011
..This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous NK1RA fosaprepitant...
- Sigma receptor agonist 2-(4-morpholinethyl)1 phenylcyclohexanecarboxylate (Pre084) increases GDNF and BiP expression and promotes neuroprotection after root avulsion injury
Group of Neuroplasticity and Regeneration, Institute of Neurosciences, Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra, Spain
J Neurotrauma 28:831-40. 2011
..Therefore, early application of Sig-1R agonist appears to be a promising therapy to improve MN survival after root avulsion...
- Benefits of mTOR kinase targeting in oncology: pre-clinical evidence with AZD8055
Oncology iMED, AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK
Biochem Soc Trans 39:456-9. 2011
..Potential ways to develop rational combinations with mTOR kinase inhibitors are also discussed. Overall, AZD8055 may provide a better therapeutic strategy than rapamycin and analogues...
- Aprepitant (EMEND): the role of substance P in nausea and vomiting
UCLA School of Medicine, Division of Hematology Oncology, Los Angeles, CA 90073, USA
J Pain Palliat Care Pharmacother 19:31-9. 2005
..Its broad range of activity against a wide variety of central and peripheral emetogenic stimuli make it potentially useful in non-chemotherapy related nausea and vomiting...
- Synergistic interaction between 17-AAG and phosphatidylinositol 3-kinase inhibition in human malignant glioma cells
Daniel R Premkumar
Department of Neurosurgery, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute Brain Tumor Center, Pittsburgh, Pennsylvania, USA
Mol Carcinog 45:47-59. 2006
- Modulation of amyloid precursor protein processing by synthetic ceramide analogues
Prince of Wales Medical Research Institute, Randwick, NSW 2031, Australia
Biochim Biophys Acta 1801:887-95. 2010
..In conclusion, this study provides novel information regarding the regulation of APP processing by synthetic ceramide analogues and reveals that the most potent of these compounds is EtDO-P4...
- The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug
Research Laboratory on Neuropeptides, Virgen del Rocío University Children s Hospital, Sevilla, Spain
Invest New Drugs 28:187-93. 2010
..These findings reported here for the first time indicate that aprepitant is a new and promising broad spectrum antitumor drug in the treatment of cancer...