- 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...
- 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...
- 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...
- 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
- 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
- LY303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells via hydrogen peroxide-mediated mitogen-activated protein kinase activation and up-regulation of death receptors
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
Cancer Res 69:1941-50. 2009
..Our findings could have implications for the use of LY30 and similar compounds for enhancing the apoptotic sensitivity of neuroblastoma cells that often become refractory to chemotherapy...
- 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
- 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...
- Application of response surface methodology to optimise ultrasonic-assisted extraction of four chromones in Radix Saposhnikoviae
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, People s Republic of China
Phytochem Anal 22:313-21. 2011
..b>Chromones are considered as one of the effective components...
- 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...
- 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...
- 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...
- 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...
- 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
- 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
- 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...
- 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...
- LY303511 amplifies TRAIL-induced apoptosis in tumor cells by enhancing DR5 oligomerization, DISC assembly, and mitochondrial permeabilization
T W Poh
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 2 Medical Drive, Singapore 117597, Singapore
Cell Death Differ 14:1813-25. 2007
..These data provide a novel mechanism of action of this small molecule with the potential for use in TRAIL-resistant tumors...
- TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells
Division of Hematology and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
Am J Hematol 85:675-86. 2010
..Our results provide the rationale for clinical evaluation of TG101209 alone or in combination with PI3K/Akt inhibitors in MM...
- Selective regulation of interleukin-10 production via Janus kinase pathway in murine conventional dendritic cells
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Kita ku, Sapporo, Japan
Cell Immunol 258:9-17. 2009
..LY294002, a specific inhibitor of PI3K, markedly inhibited the DC production of IL-10. Thus, JAK-PI3K axis appeared to be responsible for the IL-10 production by DCs...
- 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...
- Respiratory syncytial virus inhibits apoptosis and induces NF-kappa B activity through a phosphatidylinositol 3-kinase-dependent pathway
Karl W Thomas
Department of Internal Medicine, University of Iowa College of Medicine and Veterans Administration Medical Center, Iowa City, Iowa 52242, USA
J Biol Chem 277:492-501. 2002
..Blockade of PI 3-K activation resulted in rapid, premature apoptosis and inhibition of RSV-stimulated NF-kappaB-dependent gene transcription...
- Cannabilactones: a novel class of CB2 selective agonists with peripheral analgesic activity
Atmaram D Khanolkar
Center for Drug Discovery, Northeastern University, 116 Mugar Hall, 360 Huntington Avenue, Boston, Massachusetts 02115 5000, USA
J Med Chem 50:6493-500. 2007
..In vitro testing revealed that the novel compounds are CB2 agonists, while in vivo testing of cannabilactones 4b and 5 found them to possess potent peripheral analgesic activity...
- The phosphatidylinositol 3-kinase/Akt pathway enhances Smad3-stimulated mesangial cell collagen I expression in response to transforming growth factor-beta1
Constance E Runyan
Department of Pediatrics, Northwestern University, Chicago, Illinois 60611, USA
J Biol Chem 279:2632-9. 2004
..This cross-talk between the Smad and PI3K pathways likely contributes to TGF-beta1 induction of glomerular scarring...
- Selective activation of cannabinoid CB2 receptors suppresses neuropathic nociception induced by treatment with the chemotherapeutic agent paclitaxel in rats
Elizabeth J Rahn
Neuroscience and Behavior Program, Department of Psychology, University of Georgia, Athens, GA 30602 3013, USA
J Pharmacol Exp Ther 327:584-91. 2008
..Our data suggest that cannabinoid CB(2) receptors may be important therapeutic targets for the treatment of chemotherapy-evoked neuropathy...
- 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...
- Comprehensive analysis of oncogenic effects of PIK3CA mutations in human mammary epithelial cells
Breast Cancer Program, Karmanos Cancer Institute, Detroit, MI 48201, USA
Breast Cancer Res Treat 112:217-27. 2008
- Toll-like receptor 4 mediates lipopolysaccharide-induced collagen secretion by phosphoinositide3-kinase-Akt pathway in fibroblasts during acute lung injury
Department of Anesthesiology, Ninth People s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
J Recept Signal Transduct Res 29:119-25. 2009
..Therefore, we infer that besides pulmonary macrophage, lung fibroblasts are also important target cells directly influenced by LPS, which may play an important role in ALI and pulmonary interstitial fibrosis...
- Inhibition of phosphatidylinositol-3-kinase and mitogen-activated protein kinase kinase 1/2 prevents melanoma development and promotes melanoma regression in the transgenic TPRas mouse model
Division of Radiation and Cancer Biology, 269 Campus Drive, CCSR S 1230, Stanford 94305, CA, USA
Mol Cancer Ther 5:3071-7. 2006
- Synthesis and function of 3-phosphorylated inositol lipids
Ludwig Institute for Cancer Research, Riding House Street, London W1W 7BS
Annu Rev Biochem 70:535-602. 2001
..This field is now moving toward a genetic dissection of 3-phosphoinositide action in a variety of model organisms. Such approaches will reveal the true role of the 3-phosphoinositides at the organismal level in health and disease...
- Neurite growth promotion by nerve growth factor and insulin-like growth factor-1 in cultured adult sensory neurons: role of phosphoinositide 3-kinase and mitogen activated protein kinase
Division of Basic Medical Sciences, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
J Neurosci Res 63:486-99. 2001
..Activation of PI 3-kinase and SNT by both NGF and IGF-1 correlated with their effects on neurite growth. These results support the hypothesis that the PI 3-kinase pathway plays an important role in neuritogenesis...
- 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...
- ErbB2-overexpressing human mammary carcinoma cells display an increased requirement for the phosphatidylinositol 3-kinase signaling pathway in anchorage-independent growth
Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA
Oncogene 20:7551-62. 2001
- Synthesis, crystal structure and DNA-binding studies of the Ln(III) complex with 6-hydroxychromone-3-carbaldehyde benzoyl hydrazone
Bao Dui Wang
College of Chemistry and Chemical Engineering and State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
J Inorg Biochem 101:1492-504. 2007
..The intrinsic binding constants of complexes 1 and 2, and L were (7.62+/-0.56)x10(6), (3.70+/-0.47)x10(6) and (2.41+/-0.46)x10(6)M(-1), respectively...
- PKB/AKT and ERK regulation of caspase-mediated apoptosis by methylseleninic acid in LNCaP prostate cancer cells
The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA
Carcinogenesis 26:1374-81. 2005
..These findings support the differential involvement of these protein kinase pathways in regulating apoptosis induction by different forms of selenium...
- 2,6-disubstituted pyran-4-one and thiopyran-4-one inhibitors of DNA-Dependent protein kinase (DNA-PK)
Jonathan J Hollick
Northern Institute for Cancer Research, School of Natural Sciences Chemistry, Bedson Building, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK
Bioorg Med Chem Lett 13:3083-6. 2003
..2-0.4 microM range...
- 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...
- Phosphorylation and regulation of Raf by Akt (protein kinase B)
Institute of Medical Virology, University of Zurich, Gloriastrasse 30 32, CH 8028 Zurich, Switzerland
Science 286:1741-4. 1999
..These observations provide a molecular basis for cross talk between two signaling pathways at the level of Raf and Akt...
- 1alpha,25-dihydroxyvitamin D(3)-induced myeloid cell differentiation is regulated by a vitamin D receptor-phosphatidylinositol 3-kinase signaling complex
Department of Medicine, The University of British Columbia, Faculties of Medicine and Science, The Research Institute of the Vancouver Hospital and Health Sciences Center, Vancouver, British Columbia, Canada
J Exp Med 190:1583-94. 1999
..These findings suggest that PI 3-kinase selectively regulates D(3)-induced monocyte differentiation, independent of any effects on p21...
- Cisplatin and PI3kinase inhibition decrease invasion and migration of human ovarian carcinoma cells and regulate matrix-metalloproteinase expression
Amer K Karam
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA
Cytoskeleton (Hoboken) 67:535-44. 2010
..Our data suggests that inhibition of ovarian cancer cell motility is mediated via down-regulation of activated MMP2, TIMP1 and TIMP2 expression under these treatment conditions...
- Activation of phosphatidylinositol 3-kinase is important for erythropoietin-induced erythropoiesis from CD34(+) hematopoietic progenitor cells
June Helen Myklebust
Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway
Exp Hematol 30:990-1000. 2002
..The aim of this was to examine the relative involvement of PI3K in the development of glycophorin A (GPA)(+) erythroid cells from normal hematopoietic progenitor cells...
- Two chromones from Peperomia vulcanica
James A Mbah
Department of Chemistry, Faculty of Science, University of Dschang, Box 67 Dschang, Cameroon
Phytochemistry 60:799-801. 2002
TWO CHROMONES: 5-hydroxy-2-(14'-(E)-nonadecenyl) chromone (1) and 5-hydroxy-2-[12'-(3",4"-methylenedioxyphenyl)dodecanyl] chromone (2), together with six known compounds have been isolated from Peperomia vulcanica Baker & C...
- Pressurized liquid extraction followed by LC-ESI/MS for analysis of four chromones in Radix Saposhnikoviae
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, P R China
J Sep Sci 33:2881-7. 2010
An efficient pressurized liquid extraction (PLE) technique was employed in extracting chromones from the roots of Saposhnikovia divaricata (Radix Saposhnikoviae). Chromones were quantified and analyzed by LC-ESI/MS...
- Suppression of pro-metastasis phenotypes expression in malignant pleural mesothelioma by the PI3K inhibitor LY294002 or the MEK inhibitor UO126
George W Cole
Section of Thoracic Oncology, Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Anticancer Res 26:809-21. 2006
- Xanthones and oxepino[2, 3-b]chromones from three endophytic fungi
Department Chemie, Universität Paderborn, Warburger Strasse 100, 33098 Paderborn, Germany
Chemistry 15:12121-32. 2009
..Preliminary studies indicated that 1, 2, and enone 7 showed antibacterial, fungicidal, and algicidal properties...
- HB-EGF-induced VEGF production and eNOS activation depend on both PI3 kinase and MAP kinase in HaCaT cells
Department of Dermatology, Kagawa University, Japan
J Dermatol Sci 55:170-8. 2009
- Therapeutic targeting of multiple signaling pathways in malignant pleural mesothelioma
Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
Oncology 68:500-10. 2005
..Furthermore, combinations of growth factor and signal transduction inhibitors may be needed to inhibit the growth of the majority of MPM cell lines, and therefore patients with MPM...
- Phosphatidylinositol 3-kinase inhibition by LY294002 radiosensitizes human cervical cancer cell lines
Christopher M Lee
Department of Radiation Oncology, University of Utah School of Medicine and Huntsman Cancer Hospital, Salt Lake City, Utah, USA
Clin Cancer Res 12:250-6. 2006
..We evaluated the radiosensitizing effect of PI3K inhibition by LY294002 on clonogenic survival, growth characteristics, and gene expression in cervical cancer cell lines (HeLa and CaSki)...
- Synthesis of a novel series of diphenolic chromone derivatives as inhibitors of NO production in LPS-activated RAW264.7 macrophages
Guo Biao Liu
Key Lab of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China
Bioorg Med Chem 18:2864-71. 2010
..Furthermore, a computational analysis of physicochemical parameters revealed that the most of the compounds possessed drug-like properties...
- Synthesis of 3-aminomethyl-2-aryl- 8-bromo-6-chlorochromones
Erik A A Wallen
Department of Chemistry, Medicinal Chemistry, Goteborg University, SE 412 96 Goteborg, Sweden
Org Lett 9:389-91. 2007
..The Cbz-protected 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones can, e.g., be used in the synthesis of chromone-based beta-turn peptidomimetics...
- Subinhibitory concentrations of farrerol reduce α-toxin expression in Staphylococcus aureus
Institute of Zoonoses, College of Animal Sciences and Veterinary Medicine, Jilin University, Changchun, China
FEMS Microbiol Lett 315:129-33. 2011
..aureus. The results show that farrerol significantly decreased, in a dose-dependent manner, the production of α-toxin by both methicillin-sensitive S. aureus and methicillin-resistant S. aureus...
- P2X7 nucleotide receptor is coupled to GSK-3 inhibition and neuroprotection in cerebellar granule neurons
Departamento de Bioquimica y Biologia Molecular IV, Facultad de Veterinaria, Universidad Complutense de Madrid, Avda Puerta de Hierro s n, Madrid 28040, Spain
Neurotox Res 15:193-204. 2009
..These results reveal that P2X(7) receptor activation could provide a relevant survival route alternative to classical neurotrophic factors...
- Preparative separation of chromones in plant extract of Saposhnikovia divaricata by high-performance counter-current chromatography
The Central Laboratory, Changchun Normal University, China, Changchun, PR China
J Sep Sci 34:520-6. 2011
Four chromones, prim-O-glucosylcimifugin, 4'-O-β-D-glucosyl-5-O-methylvisamminol, cimifugin and sec-O-glucosylhamaudol, were isolated and purified from Saposhnikovia divaricata for the first time by high-performance counter-current ..
- Intrathecal cannabilactone CB(2)R agonist, AM1710, controls pathological pain and restores basal cytokine levels
Jenny L Wilkerson
Department of Neurosciences, University of New Mexico, Albuquerque, NM 87131, USA
Pain 153:1091-106. 2012
..Cannabilactone CB(2)R agonists are emerging as anti-inflammatory agents with pain therapeutic implications...
- Overexpression of interferon-gamma-inducible GTPase inhibits coxsackievirus B3-induced apoptosis through the activation of the phosphatidylinositol 3-kinase/Akt pathway and inhibition of viral replication
Huifang M Zhang
Department of Pathology and Laboratory Medicine, University of British Columbia MRL The iCAPTUR4E Centre, St Paul s Hospital, Vancouver, British Columbia V6Z 1Y6, Canada
J Biol Chem 278:33011-9. 2003
- Phosphatidylinositol 3-kinase in cumulus cells is responsible for both suppression of spontaneous maturation and induction of gonadotropin-stimulated maturation of porcine oocytes
Laboratory of Animal Reproduction, Graduate School of Biosphere Science, Hiroshima University, Higashi Hiroshima, Hiroshima, 739 8528, Japan
J Endocrinol 179:25-34. 2003
..Judging from these results, it is estimated that PI 3-kinase in cumulus cells is required for both the suppression of spontaneous meiotic resumption and the induction of gonadotropin-stimulated meiotic resumption...
- Enhancement of the dissolution rate and gastrointestinal absorption of pranlukast as a model poorly water-soluble drug by grinding with gelatin
Department of Pharmaceutics, Hokkaido Pharmaceutical University, 7 1 Katsuraoka cho, Otaru city 047 0264, Japan
Int J Pharm 347:71-8. 2008
..Grinding a poorly water-soluble drug with gelatin is a useful method of enhancing its gastrointestinal absorption...
- The effect of an oral leukotriene antagonist, ONO-1078, on allergen-induced immediate bronchoconstriction in asthmatic subjects
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan
J Allergy Clin Immunol 92:507-12. 1993
..0 10 minutes after the exposure. CONCLUSIONS: Therefore, we conclude that cysteinyl leukotrienes primarily mediate a later part of immediate airway obstruction after allergen exposure...
- Synthesis of 2-alkyl-substituted chromone derivatives using microwave irradiation
Department of Chemistry, Medicinal Chemistry, University of Gothenburg, SE 41296 Goteborg, Sweden
J Org Chem 74:2755-9. 2009
..The 4-chromanones could be further converted into highly functionalized 2,3,6,8-tetrasubstituted chromones in which a 3-substituent (acetate, amine, or bromine) was introduced via straightforward chemical transformations...
- Pharmacological characterization of AM1710, a putative cannabinoid CB2 agonist from the cannabilactone class: antinociception without central nervous system side-effects
Elizabeth J Rahn
Program in Neuroscience, Biomedical and Health Sciences Institute, University of Georgia, Athens, GA, United States
Pharmacol Biochem Behav 98:493-502. 2011
..The observed pattern of pharmacological specificity produced by AM1710 is consistent with limited blood brain barrier penetration of this compound and absence of CNS side-effects...
- Involvement of estrogen receptor-β in farrerol inhibition of rat thoracic aorta vascular smooth muscle cell proliferation
Qun yi Li
The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
Acta Pharmacol Sin 32:433-40. 2011
..Reporter gene and receptor binding assays were employed to study the interaction between farrerol and estrogen receptors (ERs)...
- Antitubercular chromones and flavonoids from Pisonia aculeata
Ming Chun Wu
Graduate Institute of Natural Products, Department of Biomedical Laboratory Science and Biotechnology, School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan 807, Republic of China
J Nat Prod 74:976-82. 2011
Three new chromones, pisonins A (1), B (2), and D (4), two new flavonoids, pisonivanone [(2S)-5,7,2'-trihydroxy-8-methylflavanone] (7) and pisonivanol [(2R,3R)-3,7-dihydroxy-5,6-dimethoxyflavanone] (8), one new isoflavonoid, pisonianone (..
- New sesquiterpenes from Ferula ferulaeoides (Steud.) Korovin. VI. Isolation and identification of three new dihydrofuro[2,3-b]chromones
Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan
Chem Pharm Bull (Tokyo) 50:675-7. 2002
..The structures were established by comprehensive spectral analysis. The biosynthetic pathway leading to these 2-prenyl-dihydrofurochromone-type sesquiterpenoids is proposed based on their structures...
- In vivo pharmacologic profile of ONO-1078: a potent, selective and orally active peptide leukotriene (LT) antagonist
Minase Research Institute, Ono Pharmaceutical Co, Ltd, Osaka, Japan
Jpn J Pharmacol 60:217-25. 1992
- Synthesis of 2,3,6,8-tetrasubstituted chromone scaffolds
Department of Chemistry, Medicinal Chemistry, Goteborg University, SE 412 96 Goteborg, Sweden
J Org Chem 71:6863-71. 2006
..The chromones are also interesting structural scaffolds, and they have for example been designed to be used as mimetics of ..
- Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation of TRPC5 cation channels
Department of Health and Human Services, Laboratory of Signal Transduction, NIEHS NIH, P O Box 12233, Research Triangle Park, NC 27709, USA
Pflugers Arch 457:757-69. 2009
..These findings indicate complex functions for regulation of TRPC5 by PIP2, and we propose that membrane polyphosphoinositides may have at least two distinct functions in regulating TRPC5 channel activity...
- Pigment epithelium-derived factor inhibits advanced glycation end-product-induced angiogenesis and stimulates apoptosis in retinal endothelial cells
Department of Biotechnology, Division of Molecular and Cellular Biology, Kalasalingam University, Anand Nagar, Krishnankoil, 626190, Tamil Nadu, India
Life Sci 85:719-31. 2009
- Activation of PI3-K/Akt pathway for thermal preconditioning to protect cultured cerebellar granule neurons against low potassium-induced apoptosis
Department of Pharmacology, Zhongshan Medical School, Sun Yat Sen University, Guangzhou 510080, China
Acta Pharmacol Sin 28:173-9. 2007
- Role of translocation in the activation and function of protein kinase B
Friedrich Miescher Institut, Maulbeerstrasse 66, CH 4056 Basel, Switzerland
J Biol Chem 272:31515-24. 1997
..Following activation the kinase detached from the membrane and translocated to the nucleus...
- Statins inhibit osteoblast migration by inhibiting Rac-Akt signaling
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata 573 0101, Japan
Biochem Biophys Res Commun 315:636-42. 2004
- PIK3CA is implicated as an oncogene in ovarian cancer
UCSF Cancer Center, University of California, San Francisco 941430 0808, USA
Nat Genet 21:99-102. 1999
..Our observations suggest PIK3CA is an oncogene that has an important role in ovarian cancer...
- A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity
JOSEPH R GARLICH
Semafore Pharmaceuticals, Indianapolis, Indiana, USA
Cancer Res 68:206-15. 2008
..The results support SF1126 as a viable pan PI3K inhibitor for phase I clinical trials in cancer and provide support for a new paradigm, the application of pan PI3K inhibitory prodrugs for the treatment of cancer...
- 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...
- Gas6 induces Akt/mTOR-mediated mesangial hypertrophy in diabetic nephropathy
Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
Kidney Int 68:552-61. 2005
..We have already reported Gas6 is involved in glomerular hypertrophy observed in diabetic nephropathy. However, the molecular mechanisms involved in glomerular hypertrophy are still unknown, especially in vivo...
- Simvastatin induces heme oxygenase-1: a novel mechanism of vessel protection
Tzong Shyuan Lee
Division of Biomedical Sciences, University of California, Riverside, CA 92521 0121, USA
Circulation 110:1296-302. 2004
..Here, we studied whether heme oxygenase-1 (HO-1), an important cytoprotective molecule, is induced by simvastatin and the role of HO-1 in the pleiotropic effects of simvastatin...
- Effects of novel inhibitors of poly(ADP-ribose) polymerase-1 and the DNA-dependent protein kinase on enzyme activities and DNA repair
Stephany J Veuger
Northern Institute for Cancer Research, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK
Oncogene 23:7322-9. 2004
..These data point to combined inhibition of PARP-1 and DNA-PK as a powerful strategy for tumor radiosensitization...
- Targeting integrins and PI3K/Akt-mediated signal transduction pathways enhances radiation-induced anti-angiogenesis
Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305 5152, USA
Radiat Res 168:125-33. 2007
..These results demonstrate that combined use of ionizing radiation, cRGD and LY294002 inhibited multiple signaling transduction pathways involved in tumor angiogenesis and enhanced radiation-induced effects on vascular endothelial cells...
- Effects of the phosphatidylinositol 3-kinase inhibitor in a mouse model of retinal neovascularization
Wen Zhen Yu
Department of Ophthalmology, Peking University People s Hospital, Beijing, PR China
Ophthalmic Res 40:19-25. 2008
..To determine the effects of LY294002, a phosphatidylinositol 3-kinase inhibitor, on suppressing experimental retinal neovascularization in an animal model of ischemic retinopathy...
- Topical treatment with inhibitors of the phosphatidylinositol 3'-kinase/Akt and Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways reduces melanoma development in severe combined immunodeficient mice
Division of Radiation and Cancer Biology, Stanford University, Stanford, California, USA
Cancer Res 64:2552-60. 2004
..These studies demonstrate that topical treatment targeting Ras effectors is efficacious, without systemic toxicities, and may prove to be useful in treating and preventing the progression of cutaneous melanoma...
- Phosphoinositide 3-kinase-gamma induces Xenopus oocyte maturation via lipid kinase activity
Molecular and Cellular Biophysics Research Unit, Medical Faculty of the Friedrich Schiller University Jena, Drackendorfer St. 1, D-07747 Jena, Germany
Biochem J 360:691-8. 2001
..Our data demonstrate that expression of PI3Kgamma in Xenopus oocytes accelerates their progesterone-induced maturation and that lipid kinase activity is required to induce this effect...
- Src transduces erythropoietin-induced differentiation signals through phosphatidylinositol 3-kinase
Department of Transfusion Medicine, School of Medicine and Environmental Health Sciences, Kagawa Medical University, Kagawa 761 0793, Japan
EMBO J 20:5666-77. 2001
..Taken together, Src transduces the erythropoietin-induced erythroid differentiation signals by regulating PI3-kinase activity...
- The PI3K pathway regulates endochondral bone growth through control of hypertrophic chondrocyte differentiation
CIHR Group in Skeletal Development and Remodeling, Department of Physiology and Pharmacology, University of Western Ontario, London, ON, N6A 5C1, Canada
BMC Dev Biol 8:40. 2008
..PI3K/Akt has been identified as a major regulator of cellular proliferation, differentiation and death in multiple cell types...
- Direct evidence for the action of phosphatidylinositol (3,4,5)-trisphosphate-mediated signal transduction in the 2-cell mouse embryo
Disciplines of Medicine and Physiology, University of Sydney, Royal North Shore Hospital, St Leonards, New South Wales 2065, Australia
Biol Reprod 77:813-21. 2007
..Since signal transduction via PI3kinase has important roles in governing the cell survival pathways, these results support the hypothesis that autocrine embryotropins, such as paf, act as survival factors...
- Signalling mechanisms mediated by the phosphoinositide 3-kinase/Akt cascade in synaptic plasticity and memory in the rat
Jennifer M Horwood
Laboratoire de Neurobiologie de l Apprentissage, de la Memoire et de la Communication, CNRS UMR 8620, Universite Paris Sud, Bat 446, 91405 Orsay, France
Eur J Neurosci 23:3375-84. 2006
..Importantly, only partial activation of Akt at its Ser473 residue was necessary to mediate these effects...
- Phosphorylation of Akt/PKB is required for suppression of cancer cell apoptosis and tumor progression in human colorectal carcinoma
First Department of Pathology, Yamagata University School of Medicine, Yamagata, Japan
Cancer 94:3127-34. 2002
..Therefore, the authors investigated phosphorylated Akt (Ser473) in colorectal carcinomas to reveal the role of PI3K signaling during the development of colorectal carcinoma...
- Induction of androgen receptor expression by phosphatidylinositol 3-kinase/Akt downstream substrate, FOXO3a, and their roles in apoptosis of LNCaP prostate cancer cells
George Whipple Laboratory for Cancer Research, Department of Pathology, The Cancer Center, University of Rochester, Rochester, New York 14642, USA
J Biol Chem 280:33558-65. 2005
..Together, our data provide the first model to explain how PI3K/Akt and AR can cooperate to control LNCaP cell growth and death under normal conditions...
- PKB/AKT is involved in resumption of meiosis in mouse oocytes
Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Rumburska 89, 277 21 Libechov, Czech Republic
Biol Cell 98:111-23. 2006
..During resumption of meiosis in starfish oocytes, MYT1, a negative regulator of CDK1, is phosphorylated by PKB in an inhibitory manner. It can imply that PKB is also involved in CDK1 activation in mammalian oocytes...
- Temperature effects on alpha-crystallin structure probed by 6-bromomethyl-2-(2-furanyl)-3-hydroxychromone, an environmentally sensitive two-wavelength fluorescent dye covalently attached to the single Cys residue
Sergiy V Avilov
Palladin Institute of Biochemistry, 9 Leontovich Str, 01030 Kiev, Ukraine
Int J Biol Macromol 36:290-8. 2005
- Somatic mutation and gain of copy number of PIK3CA in human breast cancer
Department of Otolaryngology Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Breast Cancer Res 7:R609-16. 2005
..Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified...
- Phosphatidylinositol 3-kinase inhibitors are a triple threat to ovarian cancer
Department of Pathology and Medicine, Institute for Cancer Genetics, New York, New York, USA
Clin Cancer Res 11:7965-6. 2005
- Phosphatidylinositol 3-kinase mediates angiogenesis and vascular permeability associated with ovarian carcinoma
Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94103 05556, USA
Clin Cancer Res 11:8208-12. 2005
..To assess the role of phosphatidylinositol-3 kinase (PI3K) inhibition in vascular permeability, angiogenesis, and vascular remodeling in tumor vessels and peritoneal lining in an athymic mouse model of i.p. human ovarian carcinoma...
- Structural insight into substrate specificity and regulatory mechanisms of phosphoinositide 3-kinases
Bloomsbury Centre for Structural Biology and Department of Biochemistry and Molecular Biology, University College London, London, UK WC1E 6BT
Trends Biochem Sci 27:426-32. 2002
..Ongoing comprehensive structural and functional studies are essential to realize the promise of PI3K isozyme-specific therapeutic agents...
- The phosphoinositide 3-kinase/Akt pathway: a new target in human renal cell carcinoma therapy
Institut National de la Sante et de la Recherche Medicale U727, University Louis Pasteur School of Medicine and Departments of Pathology and Urology, Hopitaux Universitaires de Strasbourg, Strasbourg, France
Cancer Res 66:5130-42. 2006
..Blood chemistries showed no adverse effects of the treatment. Our results suggest an important role of PI3K/Akt inhibitors as a potentially useful treatment for patients with renal cell carcinoma...
- Phosphatidylinositol 3-kinase inhibition enhances human sperm motility
Dipartimenti di Fisiopatologia Clinica, , , Italy
Hum Reprod 16:1931-7. 2001
..CONCLUSIONS: Our results suggest a negative role for PI3K in the development and maintenance of sperm motility and suggest a possible use of PI3K inhibitors to enhance motility in cases of asthenozoospermia...
- Excited-state intramolecular proton transfer distinguishes microenvironments in single- and double-stranded DNA
Andrey S Klymchenko
Photophysique des Interactions Biomoleculaires, UMR 7175 du CNRS, Faculte de Pharmacie, Universite Louis Pasteur, 67401, Illkirch, France
J Phys Chem B 112:12050-5. 2008
..Consequently, ESIPT-based dyes are promising for monitoring the interaction of polycationic molecules with DNA and probing the microenvironment of their DNA binding sites...
- Vps34p required for yeast vacuolar protein sorting is a multiple specificity kinase that exhibits both protein kinase and phosphatidylinositol-specific PI 3-kinase activities
J H Stack
Division of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego School of Medicine, La Jolla 92093 0668
J Biol Chem 269:31552-62. 1994
..On the basis of the role for Vps34p in vacuolar protein sorting, we propose that the production of a specific phosphoinositide, PtdIns(3)P, is involved in regulating intracellular protein sorting reactions in eukaryotic cells...
- PTEN and phosphatidylinositol 3'-kinase inhibitors up-regulate p53 and block tumor-induced angiogenesis: evidence for an effect on the tumor and endothelial compartment
Jing Dong Su
Section of Hematology Oncology, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46204, USA
Cancer Res 63:3585-92. 2003
..Our data provide the first preclinical evidence for the in vivo efficacy for LY294002 in the treatment of malignant gliomas...
- Estradiol rapidly activates Akt via the ErbB2 signaling pathway
Gerald E Stoica
Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA
Mol Endocrinol 17:818-30. 2003
..Taken together, our data suggest that estradiol, bound to membrane ERalpha, interacts with and activates an ErbB dimer containing ErbB2, inducing activation of PI 3-K/Akt...
- alpha5beta1 integrin protects intestinal epithelial cells from apoptosis through a phosphatidylinositol 3-kinase and protein kinase B-dependent pathway
J W Lee
Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7365, USA
Mol Biol Cell 11:1973-87. 2000
..Thus, the alpha5beta1 integrin seems to protect intestinal epithelial cells against proapoptotic stimuli by selectively enhancing the activity of the PI-3-kinase/Akt survival pathway...
- Phosphatidylinositol 3-kinase and mTOR mediate lipopolysaccharide-stimulated nitric oxide production in macrophages via interferon-beta
S L Weinstein
Department of Biology, San Francisco State University, CA 94132, USA
J Leukoc Biol 67:405-14. 2000
..Together, these data suggest that PI 3-kinase, mTOR, and possibly p70 S6 kinase mediate LPS-induced NO production by regulating the secretion of interferon-beta and by a second undefined mechanism...
- Targeting the phosphatidylinositol 3-kinase/Akt pathway for enhancing breast cancer cells to radiotherapy
Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
Mol Cancer Ther 2:353-60. 2003
..Our data suggest that Akt may be a potential target for enhancing the response to radiotherapy in patients with breast cancer...