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Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activityPatrick Dorr
Discovery Biology, Pfizer Global Research and Development Sandwich Laboratories, Kent CT13 9NJ, United Kingdom
Antimicrob Agents Chemother 49:4721-32. 2005..Clinical trials are ongoing to further investigate the potential of using maraviroc for the treatment of HIV-1 infection and AIDS...
A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5John C Tilton
Department of Microbiology, University of Pennsylvania, 301C Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
J Virol 84:10863-76. 2010....
A pièce de resistance: how HIV-1 escapes small molecule CCR5 inhibitorsJohn P Moore
Weill Medical College of Cornell University, New York, NY 10065, USA
Curr Opin HIV AIDS 4:118-24. 2009..We review what has been learned from in-vitro resistance studies, and how this relates to what is being seen, or can be anticipated, in clinical studies...
HIV-1 escape from the CCR5 antagonist maraviroc associated with an altered and less-efficient mechanism of gp120-CCR5 engagement that attenuates macrophage tropismMichael Roche
Centers for Virology, Monash University, Australia
J Virol 85:4330-42. 2011....
Population-based V3 genotypic tropism assay: a retrospective analysis using screening samples from the A4001029 and MOTIVATE studiesRachel A McGovern
BC Centre for Excellence in HIV AIDS, St Paul s Hospital, Vancouver, British Columbia, Canada
AIDS 24:2517-25. 2010..This analysis retrospectively examined the performance of population-based sequence analysis of HIV-1 env V3-loop to predict coreceptor tropism...
Clinical outcome in resistant HIV-2 infection treated with raltegravir and maravirocDarius Armstrong-James
Imperial College, St Stephens AIDS Trust, Chelsea and Westminster Hospital, London, UK
Antiviral Res 86:224-6. 2010..Further studies are required to assess the clinical efficacy of maraviroc in HIV-2 infection...
Effects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteersSamantha Abel
Pfizer Global R and D, Sandwich, UK
Br J Clin Pharmacol 65:27-37. 2008..To evaluate the influence of cytochrome P450 (CYP) 3A4 inhibitors on the clinical pharmacokinetics of maraviroc, a novel CCR5 antagonist...
Preclinical assessment of the distribution of maraviroc to potential human immunodeficiency virus (HIV) sanctuary sites in the central nervous system (CNS) and gut-associated lymphoid tissue (GALT)D K Walker
Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Sandwich, UK
Xenobiotica 38:1330-9. 2008....
Primary genotypic resistance of HIV-1 to CCR5 antagonists in CCR5 antagonist treatment-naive patientsCathia Soulie
UMPC Université Paris 06, Paris, France
AIDS 22:2212-4. 2008..The V3 loop region was rather polymorphic, and 7.3% of patients showed viruses with combinations of mutations in V3 loop previously described to be involved in maraviroc resistance, a licensed CCR5 antagonist...
Protection of rhesus macaques from vaginal infection by vaginally delivered maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptorRonald S Veazey
Tulane National Primate Research Center, Covington, LA, USA
J Infect Dis 202:739-44. 2010..These findings validate MVC development as a vaginal microbicide for women and should guide clinical programs...
Assessing theoretical risk and benefit suggested by genetic association studies of CCR5: experience in a drug development programme for maravirocJeremy Wheeler
Pfizer Research and Development, Sandwich, Kent, UK
Antivir Ther 12:233-45. 2007..There was, however, evidence to suggest rheumatoid arthritis as a potential therapeutic target for a CCR5 antagonist. Clinical evidence would be required to confirm these findings...
Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagonist maraviroc utilize inhibitor-bound receptor for entryMike Westby
Globel Research and Development, Pfizer Ltd, Sandwich Labs, Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom
J Virol 81:2359-71. 2007..This hypothesis was further corroborated by the observation that a high concentration of maraviroc blocks the activity of aplaviroc against maraviroc-resistant virus...
Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonistsRama Kondru
Department of Medicinal Chemistry, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304, USA
Mol Pharmacol 73:789-800. 2008..The fully mapped binding pocket of CCR5 is being used for structure-based design and lead optimization of novel anti-HIV CCR5 inhibitors with improved potency and better resistance profile...
Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoirMike Westby
Pfizer Global Research and Development, Sandwich, United Kingdom
J Virol 80:4909-20. 2006..Importantly, in all three patients, circulating virus reverted to predominantly CCR5 tropic following cessation of maraviroc...
Subgroup analyses of maraviroc in previously treated R5 HIV-1 infectionGerd Fatkenheuer
Universitätsklinik Köln, Cologne, Germany
N Engl J Med 359:1442-55. 2008....
Inhibition of inflammatory corneal angiogenesis by TNP-470A M Joussen
Department of Vitreoretinal Surgery, Center for Ophthalmology, University of Cologne, Koln, Germany
Invest Ophthalmol Vis Sci 42:2510-6. 2001..Topical and systemic delivery of the drug were investigated in a murine model as well as inhibition of endothelial cell proliferation in vitro and in vivo...
TNP-470, an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental modelYoko Yoshio
Second Department of Internal Medicine, Division of Renal Care Unit, Nagasaki University School of Medicine, Nagasaki, Japan
Kidney Int 66:1677-85. 2004..The aim of the present study was to evaluate the effect of TNP-470, an anti-angiogenic compound, on the development of peritoneal fibrosis induced by chlorhexidine gluconate (CG)...
Treatment of HIV infection with the CCR5 antagonist maravirocWiete Kromdijk
Slotervaart Hospital, Department of Pharmacy and Pharmacology, Louwesweg 6, 1066 EC Amsterdam, The Netherlands
Expert Opin Pharmacother 11:1215-23. 2010..New drug classes are thus required. Maraviroc is the first chemokine receptor 5 antagonist approved for use in treatment experienced HIV patients with a R5-tropic virus...
In vitro effect of anti-human immunodeficiency virus CCR5 antagonist maraviroc on chemotactic activity of monocytes, macrophages and dendritic cellsR Rossi
Department of Public Health and Infectious Diseases, Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University, Rome
Clin Exp Immunol 166:184-90. 2011..The drug might have a potential role in the down-regulation of HIV-associated chronic inflammation by blocking the recirculation and trafficking of MO and MDC...
Effects of maraviroc and efavirenz on markers of immune activation and inflammation and associations with CD4+ cell rises in HIV-infected patientsNicholas Funderburg
Case Western Reserve University, Cleveland, Ohio, United States of America
PLoS ONE 5:e13188. 2010..Maraviroc treatment for HIV-1 infected patients results in larger CD4(+) T cell rises than are attributable to its antiviral activity alone. We investigated whether this is due to modulation of T cell activation and inflammation...
Tumor cytotoxicity and endothelial Rac inhibition induced by TNP-470 in anaplastic thyroid cancerDorit Nahari
Department of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9156, USA
Mol Cancer Ther 6:1329-37. 2007..In endothelial cells, TNP-470 prevented vascular endothelial growth factor-induced endothelial permeability, intercellular gap formation, and ruffle formation by preventing Rac1 activation...
C-C chemokine receptor type 5 (CCR5) utilization of transmitted and early founder human immunodeficiency virus type 1 envelopes and sensitivity to small-molecule CCR5 inhibitorsQinxue Hu
Centre for Infection and Immunity, St George s University of London, London, UK
J Gen Virol 91:2965-73. 2010..Taken together, these findings demonstrate that T/F R5 Envs are heterogeneous with respect to the mechanisms of CCR5 utilization. These data may have implications for therapeutic and prophylactic use of CCR5-based antiretrovirals...
Amino-alkyl-cyclohexanes are novel uncompetitive NMDA receptor antagonists with strong voltage-dependency and fast blocking kinetics: in vitro and in vivo characterizationC G Parsons
Department of Pharmacology, Merz Co, Frankfurt am Main, Germany
Neuropharmacology 38:85-108. 1999..The 36 amino-alkyl-cyclohexanes tested displaced [3H]-(+)-MK-801 binding to rat cortical membranes with K(i)s between 1.5 and 143 microM...
Amino-alkyl-cyclohexanes as a novel class of uncompetitive NMDA receptor antagonistsW Danysz
Merz Co, Eckenheimer Landstrasse 100 104, Frankfurt, 60318, Germany
Curr Pharm Des 8:835-43. 2002..The present review describes the rational for developing amino-alkyl-cyclohexanes, as new uncompetitive NMDA receptor antagonists based on our positive experience with memantine which has been ..
Treatment with CCR5 antagonists: which patient may have a benefit?M C Mueller
Department of Infectious Diseases, Med Poliklinik, University Hospital of Munich, Campus Innenstadt, Pettenkoferstr 8a, 80336 Munich, Germany
Eur J Med Res 12:441-52. 2007..Clinical efficacy in patients from regions with A and D predominance should be studied in future trials. In conclusion, MVR will be of benefit for patients in various treatment situations and regions...
Cerebrospinal fluid maraviroc concentrations in HIV-1 infected patientsAylin Yilmaz
Department of Infectious Diseases, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
AIDS 23:2537-40. 2009..63 ng/ml (range 1.83-12.2). CSF samples exceeded the median EC90 for maraviroc (0.57 ng/ml) by at least three-fold. The CSF levels of maraviroc found in this study likely contribute to viral suppression in the CSF...
Angiostatic agents prevent the development of endometriosis-like lesions in the chicken chorioallantoic membraneAnnemiek W Nap
Department of Obstetrics and Gynaecology, Research Institute Growth and Development (GROW, Maastricht University and University Hospital, Maastricht, The Netherlands
Fertil Steril 83:793-5. 2005....
Maraviroc-containing regimen suppresses HIV replication in the cerebrospinal fluid of patients with neurological symptomsGiovanna Melica
Department of Clinical Immunology, Henri Mondor Hospital, Université Paris XII Creteil, Creteil, France
AIDS 24:2130-3. 2010..The median (range) maraviroc concentration in plasma was 347 ng/ml (123-2678). Four patients had CSF concentrations above the protein-adjusted inhibitory concentration (IC90) of 0.57 ng/ml (0.06-10.7) with a median of 102 ng/ml (35-173)...
Assessment of the absorption, metabolism and absolute bioavailability of maraviroc in healthy male subjectsSamantha Abel
Pfizer Global R and D, Sandwich, UK
Br J Clin Pharmacol 65:60-7. 2008..v.) maraviroc and determine the absolute bioavailability of oral maraviroc. Metabolite profiling was also conducted. Data from both of these studies were used to construct a mass-balance model for maraviroc...
Maraviroc concentrates in the cervicovaginal fluid and vaginal tissue of HIV-negative womenJulie B Dumond
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill Eshelman School of Pharmacy, Chapel Hill, NC 27599 7360, USA
J Acquir Immune Defic Syndr 51:546-53. 2009..To compare single- and multiple-dose maraviroc exposures in cervicovaginal fluid (CVF) and vaginal tissue (VT) with blood plasma (BP) and quantify maraviroc protein binding in CVF...
Raltegravir, maraviroc, etravirine: an effective protease inhibitor and nucleoside reverse transcriptase inhibitor-sparing regimen for salvage therapy in HIV-infected patients with triple-class experienceSilvia Nozza
Department of Infectious Diseases, San Raffaele Scientific Institute, Italy
AIDS 24:924-8. 2010..Although long-term safety needs further study, this protease inhibitor and nucleoside analogue-sparing regimen showed sustained efficacy...
Pharmacokinetics, safety and tolerability of a single oral dose of maraviroc in HIV-negative subjects with mild and moderate hepatic impairmentSamantha Abel
Pfizer Global Research and Development, Sandwich, UK
Antivir Ther 14:831-7. 2009..The objective of this study was to evaluate the pharmacokinetics of maraviroc in subjects with mild or moderate hepatic impairment compared with subjects with normal hepatic function. Safety and tolerability were also assessed...
Post-exposure prophylaxis with a maraviroc-containing regimen after occupational exposure to a multi-resistant HIV-infected source personFrédéric Méchaï
1 AP HP, Internal Medicine and Infectious Diseases Department, Bicetre University Hospital, Paris XI University, Le Kremin Bicêtre, France
J Med Virol 80:9-10. 2008..Post-exposure prophylaxis was well tolerated, with no increase in liver function tests. The health care worker remained HIV-negative after a 6-month follow-up...
Reviews of anti-infective agents: maraviroc: the first of a new class of antiretroviral agentsRodger D MacArthur
Wayne State University, Detroit, Michigan, USA
Clin Infect Dis 47:236-41. 2008..HIV-1 mechanisms of resistance to maraviroc, assays to determine viral coreceptor use (tropism), drug safety, and clinical use of maraviroc are discussed at length...
A pharmacokinetic-pharmacodynamic model to optimize the phase IIa development program of maravirocMaria C Rosario
Department of Clinical Pharmacology, Pfizer Clinical R and D, Groton, CT 06340, USA
J Acquir Immune Defic Syndr 42:183-91. 2006....
Insulin glargine in combination with nateglinide in people with Type 2 diabetes: a randomized placebo-controlled trialU K Dashora
School of Clinical Medical Sciences Diabetes, University of Newcastle upon Tyne, UK
Diabet Med 24:344-9. 2007..To determine the effect of adding nateglinide to therapy with insulin glargine in adults with Type 2 diabetes previously treated with insulin and with poor blood glucose control...
TNP-470 blockage of VEGF synthesis is dependent on MAPK/COX-2 signaling pathway in PDGF-BB-activated hepatic stellate cellsYan Qing Wang
Center for the Study of Liver Disease, Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong
Biochem Biophys Res Commun 341:239-44. 2006..In summary, our findings suggest that TNP-470 exhibits the observed anti-angiogenic properties in activated HSCs by targeting the COX-2/phospho-p44/42 MAPK pathway to inhibit VEGF production...
Nateglinide improves postprandial hyperglycemia and insulin secretion in renal transplant recipientsMonica Hagen Voytovich
Section of Nephrology, Department of Medicine, Rikshospitalet Radiumhospitalet HF, University of Oslo, Oslo, Norway
Clin Transplant 21:246-51. 2007..Our main objective was to investigate the safety and effect of nateglinide treatment on postprandial plasma glucose excursions and insulin secretion in RTR with PPHG...
Reduction of vascular and permeable regions in solid tumors detected by macromolecular contrast magnetic resonance imaging after treatment with antiangiogenic agent TNP-470Zaver M Bhujwalla
Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Clin Cancer Res 9:355-62. 2003..Magnetic resonance imaging (MRI) is one such noninvasive technique that is routinely used clinically...
Targeting postprandial hyperglycemia: a comparative study of insulinotropic agents in type 2 diabetesMary F Carroll
Internal Medicine Endocrinology, University of New Mexico, Albuquerque, New Mexico 87131, USA
J Clin Endocrinol Metab 88:5248-54. 2003....
Restoration of early insulin secretion after a meal in type 2 diabetes: effects on lipid and glucose metabolismG Dimitriadis
2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University Medical School, Athens, Greece
Eur J Clin Invest 34:490-7. 2004..In type 2 diabetes (T2D) insulin secretion after a meal is delayed; this may have an impact on the development of hyperglycaemia and hyperlipidaemia...
Nateglinide alone or with metformin safely improves glycaemia to target in patients up to an age of 84J U Weaver
Queen Elizabeth Hospital, University of Newcastle upon Tyne, Tyne and Wear, UK
Diabetes Obes Metab 6:344-52. 2004....
Comparison of repaglinide and nateglinide in combination with metformin: response to Raskin et alMichelle A Baron
Diabetes Care 26:3361-2; author reply 3362-3. 2003
Beta-cell function in mild type 2 diabetic patients: effects of 6-month glucose lowering with nateglinideAndrea Mari
Institute of Biomedical Engineering, National Research Council, Corso Stati Uniti 4, 35127 Padua, Italy
Diabetes Care 28:1132-8. 2005....
Repaglinide versus nateglinide monotherapy: a randomized, multicenter studyJulio Rosenstock
Dallas Diabetes and Endocrine Center, 7777 Forest Lane, Suite C618, Dallas, TX 75230, USA
Diabetes Care 27:1265-70. 2004..A randomized, parallel-group, open-label, multicenter 16-week clinical trial compared efficacy and safety of repaglinide monotherapy and nateglinide monotherapy in type 2 diabetic patients previously treated with diet and exercise...
A placebo-controlled crossover study comparing the effects of nateglinide and glibenclamide on postprandial hyperglycaemia and hyperinsulinaemia in patients with type 2 diabetesA H Barnett
Department of Medicine, Birmingham Heartlands Hospital, University of Birmingham, Birmingham, UK
Diabetes Obes Metab 6:104-13. 2004....
Clinical pharmacokinetics of nateglinide: a rapidly-absorbed, short-acting insulinotropic agentJames F McLeod
Novartis Pharmaceuticals, East Hanover, New Jersey 07936, USA
Clin Pharmacokinet 43:97-120. 2004..Further investigation is required to determine if nateglinide inhibition of postprandial glucose excursions will help to prevent diabetic complications or preserve pancreatic beta-cell function...
Antiangiogenesis therapy for endometriosisAnnemiek W Nap
Department of Obstetrics and Gynecology, Research Institute for Growth and Development, Maastricht University and University Hospital, 6202 AZ Maastricht, The Netherlands
J Clin Endocrinol Metab 89:1089-95. 2004..This suggests that the use of angiostatic agents may be promising as a therapy for endometriosis...
Sulfonylurea induced beta-cell apoptosis in cultured human isletsKathrin Maedler
Division of Endocrinology and Diabetes, University Hospital, CH-8091 Zurich, Switzerland
J Clin Endocrinol Metab 90:501-6. 2005....
Complete remission of Bomirski Ab amelanotic melanoma in hamsters treated with the angiogenesis inhibitor TNP-470A Mysliwski
Department of Histology and Immunology University of Gdansk, Gdansk, 80 210 Poland
Neoplasma 49:319-22. 2002..Thus, Ab melanoma can be effectively cured with TNP-470 angiogenesis inhibitor when the substance is applied locally...
Differential interactions of nateglinide and repaglinide on the human beta-cell sulphonylurea receptor 1Ann Maria K Hansen
Discovery, Novo Nordisk A/S, Bagsvaerd, Denmark. University Laboratory of Physiology, Oxford University, Oxford, U.K
Diabetes 51:2789-95. 2002..These results are discussed in terms of a conformational analysis of the drug molecules...
Identilication of the novel cycloaliphatic brominated flame retardant 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane in Canadian Arctic beluga (Delphinapterus leucas)Gregg T Tomy
Department of Fisheries and Oceans, Arctic Aquatic Research Division, Winnipeg, MB, R3T 2N6 Canada
Environ Sci Technol 42:543-9. 2008..Observed concentrations of the beta-isomer as measured by HRMS ranged from 1.1 to 9.3 ng/g (lipid weight)...
Maraviroc: a CCR5-receptor antagonist for the treatment of HIV-1 infectionSharon S Lieberman-Blum
Pharmacy Service, James J Peters Veterans Affairs Medical Center, Bronx, New York 10468, USA
Clin Ther 30:1228-50. 2008..It is approved by the US Food and Drug Administration (FDA) for use in combination with other antiretroviral agents in treatment-experienced patients infected with multidrug-resistant, CCR5-tropic HIV-1...
Effects of nateglinide and glibenclamide on prothrombotic factors in naïve type 2 diabetic patients treated with metformin: a 1-year, double-blind, randomized clinical trialGiuseppe Derosa
Department of Internal Medicine and Therapeutics, University of Pavia, Italy
Intern Med 46:1837-46. 2007..To evaluate the effect on coagulation and fibrinolysis parameters and on non-conventional cardiovascular risk factors of metformin plus nateglinide or glibenclamide in naïve type 2 diabetes patients...
Insulin exocytosis in Goto-Kakizaki rat beta-cells subjected to long-term glinide or sulfonylurea treatmentJunko Kawai
Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181 8611, Japan
Biochem J 412:93-101. 2008..We conclude that treatment of GK rats with nateglinide and glibenclamide varies in long-term effects on beta-cell functions; nateglinide treatment appears overall to be more beneficial...
Nateglinide, but not repaglinide, stimulates growth hormone release in rat pituitary cells by inhibition of K channels and stimulation of cyclic AMP-dependent exocytosisJesper Gromada
Novo Nordisk A/S, Novo Alle, DK-2880 Bagsvaerd, Denmark
Eur J Endocrinol 147:133-42. 2002..By contrast, the effect of repaglinide was confined to inhibition of the K(ATP) channels...
Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetesE S Horton
Joslin Diabetes Center, Boston, Massachusetts 02215, USA
Diabetes Care 23:1660-5. 2000....
Pharmacokinetics and metabolism of nateglinide in humansM L Weaver
Drug Metabolism and Pharmacokinetics, Preclinical Safety, Novartis Institute for Biomedical Research, East Hanover, New Jersey 07936, USA
Drug Metab Dispos 29:415-21. 2001..Glucuronic acid conjugates resulting from direct glucuronidation of the carboxylic acid were also present. The major metabolite in plasma and urine was the result of hydroxylation of the methine carbon of the isopropyl group...
A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1Michael Saag
School of Medicine, University of Alabama, Birmingham, AL 35294 2050, USA
J Infect Dis 199:1638-47. 2009..A phase 2b study was conducted to determine the safety and efficacy of maraviroc in combination with optimized background therapy in treatment-experienced patients infected with dual- or mixed-tropic HIV-1...
Insulinotropic meglitinide analoguesA Dornhorst
Department of Metabolic Medicine, Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, Du Cane Road, W12 0NN, London, UK
Lancet 358:1709-16. 2001..However, one hope for newer combinations of diabetic drugs is that the functional life of the beta cell can be extended, thereby delaying the need for insulin injections...
Decreased blood glucose excursion by nateglinide ameliorated neuropathic changes in Goto-Kakizaki rats, an animal model of non-obese type 2 diabetesYoshiro Kitahara
Pharmaceutical Research Laboratories, Ajinomoto, Kawasaki, Japan
Metabolism 51:1452-7. 2002..These results suggest that meticulous control of postprandial hyperglycemia is essential to inhibit the development of neuropathy in type 2 diabetes...
A Phase I and pharmacokinetic study of TNP-470 administered weekly to patients with advanced cancerP Bhargava
Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA
Clin Cancer Res 5:1989-95. 1999..v over 4 h. The principal DLT was neurotoxicity, which appeared to be dose-related and was completely reversible. On the basis of the short plasma t(1/2) of TNP-470, exploration of a prolonged i.v. infusion schedule is warranted...
CD4+ T-cell restoration after 48 weeks in the maraviroc treatment-experienced trials MOTIVATE 1 and 2David M Asmuth
University of California Davis, Sacramento, CA, USA
J Acquir Immune Defic Syndr 54:394-7. 2010..To determine factors associated with CD4 responses to maraviroc (MVC)-containing regimens in treatment-experienced patients...
Identification of the brominated flame retardant 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane as an androgen agonistAnders Larsson
Orebro Life Science Center, Department of Natural Sciences, Orebro University, SE-701 82 Orebro, Sweden
J Med Chem 49:7366-72. 2006..The remaining BFRs did not successfully interact with the ligand pocket, were not able to replace a synthetic androgen from the receptor, and failed to activate the receptor...
Combination therapy with nateglinide and a thiazolidinedione improves glycemic control in type 2 diabetesJulio Rosenstock
Dallas Diabetes and Endocrine Center, Dallas, Texas, USA
Diabetes Care 25:1529-33. 2002....
TNP-470 inhibits growth and the production of vascular endothelial growth factor of uterine carcinosarcoma cells in vitroM Emoto
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Japan
Anticancer Res 20:601-4. 2000..This is the first study to examine the inhibitory and anti-angiogenic effects of angiogenesis inhibitor TNP-470, a synthetic analogue of fumagillin, for human uterine carcinosarcoma in vitro...
Nateglinide, a non-sulfonylurea rapid insulin secretagogue, increases pancreatic islet blood flow in ratsMasanori Iwase
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3 1 1, Higashi ku, Fukuoka 812 8582, Japan
Eur J Pharmacol 518:243-50. 2005..Our results indicated that nateglinide acutely increased islet blood flow at least in part through a nitric oxide-dependent mechanism...
Minute dosages of alpha(nu)beta3-targeted fumagillin nanoparticles impair Vx-2 tumor angiogenesis and development in rabbitsPatrick M Winter
Washington University Medical School, Campus Box 8215, 4320 Forest Park Ave, St Louis, MO 63108, USA
FASEB J 22:2758-67. 2008..These results suggest that alpha(nu)beta(3)-targeted fumagillin nanoparticles could provide a safe and effective means to deliver MetAP2 inhibitors alone or in combination with cytotoxic or immunotherapy...
Evaluation of the antiangiogenic potential of AQ4NMartin O'Rourke
Biomedical Sciences Research Institute, University of Ulster, Coleraine, Northern Ireland, United Kingdom
Clin Cancer Res 14:1502-9. 2008..AQ4N is structurally similar to mitoxantrone and was evaluated for antiangiogenic properties without the need for bioreduction...
Antiangiogenic agents: studies on fumagillin and curcumin analogsM S Furness
Department of Chemistry and Biochemistry, 435 New Science Building, PO Box 26170, University of North Carolina at Greensboro, Greensboro, NC 27402, USA
Curr Pharm Des 11:357-73. 2005..Both compounds have been shown to have antiangiogenic properties in vitro and in vivo. This paper describes efforts to design and prepare fumagillin and curcumin analogs and evaluate their corresponding antiangiogenic activities...
Fumagillin treatment of hepatocellular carcinoma in rats: an in vivo study of antiangiogenesisI-Shyan Sheen
Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan, China
World J Gastroenterol 11:771-7. 2005..A possible mechanism is fumagillin-induced inhibition of MetAP-2, which plays an essential role in endothelial cell proliferation. Inhibition of MetAP-2 also results in inhibition of Bcl-2 and telomerase activity...
Characterization of the active site and insight into the binding mode of the anti-angiogenesis agent fumagillin to the manganese(II)-loaded methionyl aminopeptidase from Escherichia coliVentris M D'souza
Department of Chemistry and Biochemistry, Utah State University, Logan, UT 84322 0300, USA
J Biol Inorg Chem 10:41-50. 2005..Therefore, the inhibitory action of this anti-angiogenesis agent on EcMetAP-I appears to involve covalent binding to a polypeptide component at or near the active site rather than direct binding to the metal ions...
Treatment of cells with the angiogenic inhibitor fumagillin results in increased stability of eukaryotic initiation factor 2-associated glycoprotein, p67, and reduced phosphorylation of extracellular signal-regulated kinasesBansidhar Datta
Department of Chemistry, Kent State University, Kent, Ohio 44242, USA
Biochemistry 43:14821-31. 2004..These results suggest that fumagillin increases the stability of p67 and its affinity to ERKs 1 and 2 and causes the inhibition of the phosphorylation of ERKs 1 and 2...
Fumagiringillin, a new fumagillin derivative from a strain of the fungus Aspergillus fumigatusWenxu Jiao
Department of Chemistry and School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch, New Zealand
J Nat Prod 67:1434-7. 2004..A new fumagillin derivative, fumagiringillin (1), has been isolated together with fumagillin (2) and 12alpha-fumitremorgin C (3) from a strain of Aspergillus fumigatus. The structures were elucidated by spectral analyses...
Small molecule inhibitors of methionine aminopeptidase type 2 (MetAP-2)Thomas Garrabrant
Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, LLC, Spring House, Pennsylvania 19477, USA
Angiogenesis 7:91-6. 2004....
Role of early insulin secretion in postglucose-loading hyperglycaemia and postfat-loading hyperlipidaemia: comparing nateglinide and glibenclamide for acute effects on insulin secretion in OLETF ratsY Mori
Department of Internal Medicine, National Hospital Organization Utsunomiya Hospital, Kawachi, Tochigi 329 1193, Japan
Diabetes Obes Metab 6:422-31. 2004..glibenclamide (GB) on increases in glucose after glucose loading and on increases in triglyceride (TG) after fat loading...
Novel inhibitors targeted to methionine aminopeptidase 2 (MetAP2) strongly inhibit the growth of cancers in xenografted nude modelEunyoung Chun
Immune-2 Team, Mogam Biotechnology Research Institute, Yongin-city Kyonggi-do, South Korea
Int J Cancer 114:124-30. 2005..In conclusion, these 4 inhibitory compounds potently exert an antiangiogenic effect to inhibit the growth of cancers in vivo and could potentially be useful for the treatment of a variety of cancers...
Synthesis and biological evaluation of novel fumagillin and ovalicin analoguesRalph Mazitschek
The Broad Institute, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02141, USA
Org Biomol Chem 3:2150-4. 2005..We also report a new synthetic approach and the determination of the anti-angiogenic properties of these compounds in endothelial cells...
Fumagillin: an anti-infective as a parent molecule for novel angiogenesis inhibitorsBenjamin Lefkove
Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA
Expert Rev Anti Infect Ther 5:573-9. 2007....
Early genetic mechanisms underlying the inhibitory effects of endostatin and fumagillin on human endothelial cellsChiara M Mazzanti
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Genome Res 14:1585-93. 2004..Because the gene expression changes occurred within 1 and 2 h of treatment, these genes might be involved in the initial pathways of angiogenesis inhibition...
FGFR1/PI3K/AKT signaling pathway is a novel target for antiangiogenic effects of the cancer drug fumagillin (TNP-470)Gregory J Chen
Department of Systems Biology and Translational Medicine, College of Medicine, The Texas A and M University System Health Science Center, College Station, Texas 77843, USA
J Cell Biochem 101:1492-504. 2007..Based on these findings, we conclude that the binding of fumagillin to the cytoplasmic domain of the FGF1 receptor inhibited FGF1-stimulated angiogenesis both in vitro and in vivo...
Design, synthesis, and antiangiogenic effects of a series of potent novel fumagillin analoguesHong Woo Lee
New Drug Research Laboratories, Chong Kun Dang Research Institute, Cheonan, South Korea
Chem Pharm Bull (Tokyo) 55:1024-9. 2007..These compounds are presently under further pharmacological evaluation studies...
A chemical and genetic approach to the mode of action of fumagillinYi Zhang
Department of Molecular, Cell, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA
Chem Biol 13:1001-9. 2006..Thus, TNP-470 selectively regulates noncanonical over canonical Wnt signaling and provides a unique means to explore and dissect the biological systems mediated by these pathways...
A noncanonical path to mechanism of actionRandall T Peterson
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
Chem Biol 13:924-6. 2006..In this issue of Chemistry & Biology, Zhang et al. make clever use of the zebrafish to study the mechanism of the angiogenesis inhibitor fumagillin and reveal that it targets the noncanonical Wnt pathway...
Fumarranol, a rearranged fumagillin analogue that inhibits angiogenesis in vivoJun Lu
Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Med Chem 49:5645-8. 2006..It is also active in a mouse model of angiogenesis in vivo. Unlike TNP-470, fumarranol does not covalently bind to MetAP2. Fumarranol may serve as a lead for a new class of angiogenesis inhibitors...
Comparison of nateglinide and gliclazide in combination with metformin, for treatment of patients with Type 2 diabetes mellitus inadequately controlled on maximum doses of metformin aloneS Ristic
Novartis Pharma, Basel, Switzerland
Diabet Med 23:757-62. 2006..To compare the effects of nateglinide plus metformin with gliclazide plus metformin on glycaemic control in patients with Type 2 diabetes...
Study of nateglinide in Japan: long-term treatment of patients with type 2 diabetesHiroto Taki
Pharmaceutical Regulatory Affairs and Quality Assurance Department, Ajinomoto Co, Inc, Tokyo, Japan
Adv Ther 23:307-24. 2006..This study showed the efficacy and safety of long-term treatment with nateglinide of patients with diabetes from various backgrounds...
[On chance discovery in rational drug design. Aspergillus fumigatus and angiogenesis]Christian Klein
Pharmazeutische Chemie, Universitat Heidelberg, Im Neuenheimer Feld 364, D 69120 Heidelberg
Pharm Unserer Zeit 36:450-1. 2007..Diese Substanz war einer der ersten niedermolekularen Angiogeneseinhibitoren und trug wesentlich dazu bei, diese therapeutische Strategie überhaupt erst interessant zu machen...
[Synthesis and insulinotropic activity of 2-benzylidenesuccinic acid derivatives]Li-mei Gao
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Yao Xue Xue Bao 40:1122-6. 2005..CONCLUSION: Part of the compounds have higher hypoglycemic activity deserve to be further investigated...
Effect of molecular chirality and side chain bulkiness on angiogenesis of haloacetylcarbamoyl-2-nitroimidazole compoundsKazuto Ohkura
Faculty of Pharmacy, Chiba Institute of Science, 3 Shiomi cho, Choshi, Chiba, Japan
Anticancer Res 27:3693-700. 2007..TXs have a chiral center and S- and R-enantiomers. Conformation analysis and molecular dynamics simulation were undertaken. Materials and..
Advances in understanding angiogenesis through molecular studiesMijung Kwon
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1201, USA
Int J Radiat Oncol Biol Phys 64:26-32. 2006..Elucidation of the pathways that mediate both angiogenic and antiangiogenic responses will help us to develop better anticancer therapies...
Different effects of SLCO1B1 polymorphism on the pharmacokinetics and pharmacodynamics of repaglinide and nateglinideAnnikka Kalliokoski
Department of Clinical Pharmacology, Helsinki University Central Hospital, FIN 00029 HUS, Finland
J Clin Pharmacol 48:311-21. 2008..Thus, in contrast to repaglinide, the disposition of nateglinide is unaffected by the SLCO1B1 c.521T>C polymorphism...
Improved prandial glucose control with lower risk of hypoglycemia with nateglinide than with glibenclamide in patients with maturity-onset diabetes of the young type 3Tiinamaija Tuomi
Department of Medicine Diabetology, Helsinki University Central Hospital, P O Box 340, FIN 00029 HUS, Helsinki, Finland
Diabetes Care 29:189-94. 2006....
Total synthesis and antiangiogenic activity of cyclopentane analogues of fumagillolByeong-Seon Jeong
New Drug Research Laboratories, Chong Kun Dang Research Institute, Cheonan 330-831, Republic of Korea
Bioorg Med Chem Lett 15:3580-3. 2005..The cyclopentane-fumagillol derivatives were synthesized from (-)-2,3-O-isopropylidene-D-erythronolactone via stereoselective glycolate Claisen rearrangement and intramolecular ester enolate alkylation as key steps...
Methionine aminopeptidase 2 over-expressed in cholangiocarcinoma: potential for drug targetKanlayanee Sawanyawisuth
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Acta Oncol 46:378-85. 2007..The inhibition of enzyme activity using MetAP2 inhibitors may be a potential strategy for long-term control of tumor development and progression in CCA patients...
Homology modeling and calculation of the cobalt cluster charges of the Encephazlitozoon cuniculi methionine aminopeptidase, a potential target for drug designFrancois Bontems
Equipe ICSN RMN, Ecole Polytechnique, F91128 Palaiseau France
Biophys Chem 105:29-43. 2003..It also suggests that the TNP-470 interact identically with both enzymes while there could be small differences in case of the fumagillin...
Angiogenesis inhibitors specific for methionine aminopeptidase 2 as drugs for malaria and leishmaniasisPent Zhang
Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA
J Biomed Sci 9:34-40. 2002..falciparum and Leishmania donavani, with IC(50) values similar to the prototype drugs. Furthermore, in the case of P. falciparum, the chloroquine-resistant strains are equally susceptible to these two compounds...
Concise stereocontrolled routes to fumagillol, fumagillin, and TNP-470David A Vosburg
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Chirality 15:156-66. 2003..Other key steps include a facile hetero-Claisen rearrangement and a site-selective Sharpless epoxidation...
Structure and function of the methionine aminopeptidasesW T Lowther
Institute of Molecular Biology, Howard Hughes Medical Institute and Department of Physics, University of Oregon, Eugene, OR 97403 1229, USA
Biochim Biophys Acta 1477:157-67. 2000....
A novel early chorioallantoic membrane assay demonstrates quantitative and qualitative changes caused by antiangiogenic substancesSusan J Hazel
Division of Veterinary Services, Institute of Medical and Veterinary Science, Adelaide, Australia
J Lab Clin Med 141:217-28. 2003..Further study of the qualitative effects of antiangiogenic treatments may be a valuable tool to increase our understanding of the angiogenic process itself...
Investigation of novel fumagillin analogues as angiogenesis inhibitorsHyung Jung Pyun
Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA
Bioorg Med Chem Lett 14:91-4. 2004..Compound (E)-3d, containing ethylpiperazinyl carbamate at C6 position, exhibited antiangiogenic effects similar to TNP-470 on matrigel plug assay and rat corneal micropocket assay...
Research Grants
- Nitrile-Containing Decalins in MedicineFRASER FLEMING; Fiscal Year: 2005..abstract_text> ..
- SECOND RECEPTORS FOR PRIMATE IMMUNODEFICIENCY VIRUSESJohn Moore; Fiscal Year: 2005..We will identify what coreceptor(s) mediate CCR5-inhibitor insensitive SIV entry in vitro. ..
- HOSTILE ENVIRONMENTS PROMOTE INVASION AND METATASISZaver Bhujwalla; Fiscal Year: 2007..The studies proposed in this application will lead to the potential identification of targets and pathways for the prevention of metastatic disease. ..
- FUSED POLYCYCLIC AMINES VIA DOUBLE ANNULATIONRobert Grossman; Fiscal Year: 2004..The yohimbine and corynanthine analogs will be tested for alpha-adrenoceptor antagonist activity. ..
- SYNTHESIS OF EUNICELLIN DITERPENES AND RELATED COMPOUNDSMATTHIAS MCINTOSH; Fiscal Year: 2003....
- STUDY OF BIOLOGICALLY ACTIVE MICROBIAL METABOLITESHEINZ FLOSS; Fiscal Year: 1993....
- SYNTHESIS OF BIOLOGICALLY ACTIVE NATURAL PRODUCTSBARRY SNIDER; Fiscal Year: 2007..In the course of these studies new methods will be developed that are of general utility for preparing drugs more economically. ..
- SYNTHESIS OF BIOLOGICALLY ACTIVE NATURAL PRODUCTSBARRY SNIDER; Fiscal Year: 2009..In the course of these studies new methods will be developed that are of general utility for preparing drugs more economically. ..
- ANTITUMOR AND ANTIVIRAL NUCLEOSIDE ANALOGUESJiri Zemlicka; Fiscal Year: 2001..In vivo activity and mechanism of action of active compounds will also be investigated. Selected analogues will also be studies as potential antitumor agents. ..
- Enantioselective Synthesis of Leustroducsin BTHOMAS HUNTER; Fiscal Year: 2005....
- Synthesis of Glycomimetics and Related StructuresDAVID MOOTOO; Fiscal Year: 2006Highly oxygenated tetrahydropyrans and cyclohexanes are of interest as biochemical probes for disease related mechanisms, and, or drug leads for new therapeutic agents...
- NON-PEPTIDE PEPTIDOMIMETICSRalph Hirschmann; Fiscal Year: 2004..Finally, we will explore (K) the pharmacokinetic profiles of our lead mimics through our collaborations with expert biologists. ..
- FUNCTIONAL ANALOGS OF THE ENEDIYNE TOXINSMARTIN SEMMELHACK; Fiscal Year: 2001..The potency of the enediyne in DNA cleavage is very sensitive to positioning on the DNA and proper design of the delivery agents is a critical component. ..
- Chrolactomycin and Okilactomycin: Novel Antitumor AgentsTodd Bosanac; Fiscal Year: 2004..An extension of the Petasis-Ferrier rearrangement will be employed to construct the tetrahydropyranone core. ..
- PROTEIN SYNTHESIS INITIATION IN ANIMAL CELLSBansidhar Datta; Fiscal Year: 2002..This research is expected to provide valuable information regarding the mechanism of protein synthesis initiation in normal, cancerous, and virus- infected animal cells. ..
- CYTOMIMETIC ORGANIC CHEMISTRYFREDRIC MENGER; Fiscal Year: 2007....
- RECENT ADVANCES IN AIDS AND HIV RESEARCHMichael Saag; Fiscal Year: 2007..CME credit for attending physicians will be provided. ..
- CHEMICAL MECHANISMS OF BIOSYNTHESISRichard Wolfenden; Fiscal Year: 2009....
