purines

Summary

Summary: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.

Top Publications

  1. ncbi Receptors for purines and pyrimidines
    V Ralevic
    School of Biomedical Sciences, Queen s Medical Centre, University of Nottingham, Nottingham, England
    Pharmacol Rev 50:413-92. 1998
  2. pmc Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme
    Odd Erik Johansen
    Boehringer Ingelheim, Asker, Norway
    Cardiovasc Diabetol 11:3. 2012
  3. ncbi Purines, purinergic receptors, and cancer
    Francesco Di Virgilio
    Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Ferrara, Italy
    Cancer Res 72:5441-7. 2012
  4. ncbi Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5
    L Meijer
    CNRS, Station Biologique, Roscoff, France
    Eur J Biochem 243:527-36. 1997
  5. ncbi Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study
    D R Owens
    University Hospital Llandough, Cardiff, UK
    Diabet Med 28:1352-61. 2011
  6. ncbi Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study
    M R Taskinen
    Department of Medicine, Helsinki University Central Hospital, Finland
    Diabetes Obes Metab 13:65-74. 2011
  7. ncbi Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial
    S Del Prato
    Department of Endocrinology and Metabolism, Section of Metabolic Diseases, University of Pisa, Pisa, Italy
    Diabetes Obes Metab 13:258-67. 2011
  8. ncbi Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin(*)
    U Graefe-Mody
    Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim, Germany
    Diabetes Obes Metab 13:939-46. 2011
  9. ncbi PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study
    Marco Guazzi
    Cardiopulmonary Unit and Department of Cardiology, University of Milano, San Paolo Hospital, Via A Di Rudini 8, Milan, Italy
    Circ Heart Fail 4:8-17. 2011
  10. pmc Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to promote resolution of inflammation
    A E Leitch
    MRC Centre for Inflammation Research, The Queen s Medical Research Institute, University of Edinburgh Medical School, Edinburgh, Scotland, UK
    Cell Death Differ 19:1950-61. 2012

Detail Information

Publications389 found, 100 shown here

  1. ncbi Receptors for purines and pyrimidines
    V Ralevic
    School of Biomedical Sciences, Queen s Medical Centre, University of Nottingham, Nottingham, England
    Pharmacol Rev 50:413-92. 1998
  2. pmc Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme
    Odd Erik Johansen
    Boehringer Ingelheim, Asker, Norway
    Cardiovasc Diabetol 11:3. 2012
    ..This study investigated the cardiovascular (CV) safety profile of the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin versus comparator treatments...
  3. ncbi Purines, purinergic receptors, and cancer
    Francesco Di Virgilio
    Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Ferrara, Italy
    Cancer Res 72:5441-7. 2012
    b>Purines were long thought to be restricted to the intracellular compartment, where they are used for energy transactions, nucleic acid synthesis, and a multiplicity of biochemical reactions...
  4. ncbi Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5
    L Meijer
    CNRS, Station Biologique, Roscoff, France
    Eur J Biochem 243:527-36. 1997
    ..Through its unique selectivity for some cyclin-dependent kinases, roscovitine provides a useful antimitotic reagent for cell cycle studies and may prove interesting to control cells with deregulated cdc2, cdk2 or cdk5 kinase activities...
  5. ncbi Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study
    D R Owens
    University Hospital Llandough, Cardiff, UK
    Diabet Med 28:1352-61. 2011
    ..0-10.0%)] by metformin and sulphonylurea combination treatment...
  6. ncbi Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study
    M R Taskinen
    Department of Medicine, Helsinki University Central Hospital, Finland
    Diabetes Obes Metab 13:65-74. 2011
    ..To evaluate the efficacy and safety of the potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin administered as add-on therapy to metformin in patients with type 2 diabetes with inadequate glycaemic control...
  7. ncbi Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial
    S Del Prato
    Department of Endocrinology and Metabolism, Section of Metabolic Diseases, University of Pisa, Pisa, Italy
    Diabetes Obes Metab 13:258-67. 2011
    ....
  8. ncbi Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin(*)
    U Graefe-Mody
    Boehringer Ingelheim Pharma GmbH and Co KG, Ingelheim, Germany
    Diabetes Obes Metab 13:939-46. 2011
    ....
  9. ncbi PDE5 inhibition with sildenafil improves left ventricular diastolic function, cardiac geometry, and clinical status in patients with stable systolic heart failure: results of a 1-year, prospective, randomized, placebo-controlled study
    Marco Guazzi
    Cardiopulmonary Unit and Department of Cardiology, University of Milano, San Paolo Hospital, Via A Di Rudini 8, Milan, Italy
    Circ Heart Fail 4:8-17. 2011
    ..In a cohort of systolic HF patients, we tested the effects of PDE5 inhibition (sildenafil) on LV ejection fraction, diastolic function, cardiac geometry, and clinical status...
  10. pmc Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to promote resolution of inflammation
    A E Leitch
    MRC Centre for Inflammation Research, The Queen s Medical Research Institute, University of Edinburgh Medical School, Edinburgh, Scotland, UK
    Cell Death Differ 19:1950-61. 2012
    ..Thus, we highlight a novel mechanism that controls both primary human neutrophil transcription and apoptosis that could be targeted by selective CDK inhibitor drugs to resolve established inflammation...
  11. ncbi Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study
    R Gomis
    Endocrinology and Diabetes Service, IDIBAPS, CIBERDEM, Hospital Clinic Villarroel, Barcelona, Spain
    Diabetes Obes Metab 13:653-61. 2011
    ..5-11.0%)...
  12. pmc Considerations when measuring myocardial perfusion reserve by cardiovascular magnetic resonance using regadenoson
    Nicole M Bhave
    Departments of Medicine and Radiology, University of Chicago, Cardiac Imaging Center, Chicago, IL 60637, USA
    J Cardiovasc Magn Reson 14:89. 2012
    ..We sought to determine the optimal regadenoson CMR protocol for quantifying myocardial perfusion reserve index (MPRi) - more specifically, whether regadenoson stress imaging should be performed before or after rest imaging...
  13. pmc DNA sequence-dependent deformability deduced from protein-DNA crystal complexes
    W K Olson
    Department of Chemistry, Rutgers University, New Brunswick, NJ 08903, USA
    Proc Natl Acad Sci U S A 95:11163-8. 1998
    ....
  14. ncbi Sildenafil citrate therapy for pulmonary arterial hypertension
    Nazzareno Galie
    Institute of Cardiology, University of Bologna, Bologna, Italy
    N Engl J Med 353:2148-57. 2005
    ....
  15. ncbi The cyclin-dependent kinase inhibitor R-roscovitine down-regulates Mcl-1 to override pro-inflammatory signalling and drive neutrophil apoptosis
    Andrew E Leitch
    MRC Centre for Inflammation Research, The Queen s Medical Research Institute, University of Edinburgh Medical School, Edinburgh, Scotland, UK
    Eur J Immunol 40:1127-38. 2010
    ..These findings suggest that key endogenous survival proteins may be the targets of CDK inhibitors and consequently may be of critical importance in the resolution of inflammation...
  16. ncbi Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells by inhibition of RNA polymerase II-dependent transcription and down-regulation of Mcl-1
    David E MacCallum
    Cyclacel Ltd, Dundee Technopole, James Lindsay Place, Dundee, United Kingdom
    Cancer Res 65:5399-407. 2005
    ..This study provides the scientific rationale for the clinical development of seliciclib for the treatment of multiple myeloma...
  17. ncbi Roscovitine targets, protein kinases and pyridoxal kinase
    Stephane Bach
    CNRS, Cell Cycle Group, UPS 2682 and UMR 2775, Station Biologique, BP 74, 29682 Roscoff Cedex, Bretagne, France
    J Biol Chem 280:31208-19. 2005
    ..These results could help in interpreting the cellular actions of (R)-roscovitine but also in guiding the synthesis of more selective roscovitine analogs...
  18. ncbi Chronic treatment with sildenafil improves energy balance and insulin action in high fat-fed conscious mice
    Julio E Ayala
    Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 2200 Pierce Ave, 702 Light Hall, Nashville, TN 37232, USA
    Diabetes 56:1025-33. 2007
    ..These results show that phosphodiesterase-5 is a potential target for therapies aimed at preventing diet-induced energy imbalance and insulin resistance...
  19. ncbi Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy
    Eiki Takimoto
    Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Ross 835, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
    Nat Med 11:214-22. 2005
    ..PDE5A inhibition may provide a new treatment strategy for cardiac hypertrophy and remodeling...
  20. pmc The effect of obesity on regadenoson-induced myocardial hyperemia: a quantitative magnetic resonance imaging study
    Edward V R DiBella
    UCAIR, Department of Radiology, University of Utah, Salt Lake City, UT, USA
    Int J Cardiovasc Imaging 28:1435-44. 2012
    ..Fixed dose regadenoson and weight adjusted adenosine produce similar measures of MPR in patients with a wide range of body sizes. Regadenoson is a potentially useful vasodilator for stress MRI studies...
  21. ncbi Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial
    Ami E Iskandrian
    University of Alabama at Birmingham, Birmingham, AL 35294 0006, USA
    J Nucl Cardiol 14:645-58. 2007
    ..Earlier phase 1 and 2 studies have shown that regadenoson has desirable features as a stress agent for myocardial perfusion imaging...
  22. ncbi Microglial activation by purines and pyrimidines
    Kazuhide Inoue
    Section of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan
    Glia 40:156-63. 2002
    Microglial activation by purines and pyrimidines is reviewed, with emphasis on the actions of adenosine 5'-triphosphate (ATP) on chemotaxis or releases of plasminogen and cytokines from microglia...
  23. ncbi Tachycardia caused by A2A adenosine receptor agonists is mediated by direct sympathoexcitation in awake rats
    Arvinder K Dhalla
    Department of Pharmacology, CV Therapeutics, Palo Alto, CA 94304, USA
    J Pharmacol Exp Ther 316:695-702. 2006
    ....
  24. ncbi Hydrogen peroxide-induced oxidative stress in MC3T3-E1 cells: The effects of glutamate and protection by purines
    Amos A Fatokun
    Institute of Biomedical and Life Sciences, Division of Neuroscience and Biomedical Systems, West Medical Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK
    Bone 39:542-51. 2006
    ..Adenosine and its receptors afforded some protection to osteoblasts against cellular death mediated partly by apoptosis and partly by necrosis...
  25. ncbi Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis
    Adriano G Rossi
    MRC Centre for Inflammation Research, Queen s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
    Nat Med 12:1056-64. 2006
    ..Thus, CDK inhibitors enhance the resolution of established inflammation by promoting apoptosis of inflammatory cells, thereby demonstrating a hitherto unrecognized potential for the treatment of inflammatory disorders...
  26. ncbi CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases
    K Bettayeb
    CNRS, Cell Cycle Group, Station Biologique, Bretagne, France
    Oncogene 27:5797-807. 2008
    ..Altogether these results show that second-generation analogues of (R)-roscovitine can be designed with improved antitumor potential...
  27. ncbi Initial clinical experience with regadenoson, a novel selective A2A agonist for pharmacologic stress single-photon emission computed tomography myocardial perfusion imaging
    Robert C Hendel
    Rush University Medical Center, Chicago, Illinois, USA
    J Am Coll Cardiol 46:2069-75. 2005
    ....
  28. ncbi Effects of age, gender, obesity, and diabetes on the efficacy and safety of the selective A2A agonist regadenoson versus adenosine in myocardial perfusion imaging integrated ADVANCE-MPI trial results
    Manuel D Cerqueira
    Departments of Nuclear Medicine and Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    JACC Cardiovasc Imaging 1:307-16. 2008
    ....
  29. ncbi The oral DPP-4 inhibitor linagliptin significantly lowers HbA1c after 4 weeks of treatment in patients with type 2 diabetes mellitus
    T Forst
    Institut für Klinische Forschung und Entwicklung GmbH, Mainz, Germany
    Diabetes Obes Metab 13:542-50. 2011
    ..To investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of linagliptin in patients with type 2 diabetes mellitus (T2DM)...
  30. ncbi The metabolism and disposition of the oral dipeptidyl peptidase-4 inhibitor, linagliptin, in humans
    Stefan Blech
    Department of Drug Metabolism, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany
    Drug Metab Dispos 38:667-78. 2010
    ..Other minor metabolites were identified by mass spectrometry and NMR investigations. However, it was concluded that the metabolites of linagliptin only play a minor role in the overall disposition and elimination of linagliptin...
  31. pmc Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma
    Noopur Raje
    Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Mayer 557, 44 Binney St, Boston, MA 02115, USA
    Blood 106:1042-7. 2005
    ..Finally, combination studies of seliciclib with doxorubicin and bortezomib show in vitro synergism, providing the rationale for testing these drug combinations to improve patient outcome in MM...
  32. ncbi Regadenoson, a selective A2A adenosine receptor agonist, causes dose-dependent increases in coronary blood flow velocity in humans
    Hsiao D Lieu
    Portola Pharmaceuticals, South San Francisco, Calif, USA
    J Nucl Cardiol 14:514-20. 2007
    ..This study characterized the dose dependence of regadenoson-induced coronary hyperemia...
  33. pmc Phosphatidylinositol 3-kinase-δ inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals
    Sarah E M Herman
    Integrated Biomedical Science Graduate Program, TheOhio State University, Columbus, OH, USA
    Blood 116:2078-88. 2010
    ..Collectively, these studies provide rationale for the clinical development of CAL-101 as a first-in-class targeted therapy for CLL and related B-cell lymphoproliferative disorders...
  34. ncbi Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study
    Ashwin A Patkar
    Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA
    Psychopharmacology (Berl) 206:479-89. 2009
    ..Mapping metabolic "signatures" can provide new insights into addictive mechanisms and potentially identify biomarkers and therapeutic targets...
  35. ncbi Molecular and functional characterization of the first nucleobase transporter gene from African trypanosomes
    Cristina Henriques
    Department of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 S W Sam Jackson Park Road, Portland, OR 97201, USA
    Mol Biochem Parasitol 130:101-10. 2003
    African trypanosomes are unable to synthesize purines and depend upon purine nucleoside and nucleobase transporters to salvage these compounds from their hosts...
  36. pmc Stretches of alternating pyrimidine/purines and purines are respectively linked with pathogenicity and growth temperature in prokaryotes
    Jon Bohlin
    Norwegian School of Veterinary Science, Oslo, Norway
    BMC Genomics 10:346. 2009
    ..Although some of these factors are a consequence of the chemical properties of purines and pyrimidines, a thorough statistical examination of the distributions of YR/RR stretches in sequenced ..
  37. ncbi Sildenafil inhibits the formation of superoxide and the expression of gp47 NAD[P]H oxidase induced by the thromboxane A2 mimetic, U46619, in corpus cavernosal smooth muscle cells
    Anthony J Koupparis
    Urology and Bristol Heart Institute, Bristol Royal Infirmary, Bristol, UK
    BJU Int 96:423-7. 2005
    ..To assess the effect of sildenafil on superoxide formation and p47(phox) (the active subunit of NADPH oxidase) expression in cultured corpus cavernosal smooth muscle cells (CVSMCs)...
  38. ncbi Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients
    T Heise
    Profil Institut für Stoffwechselforschung GmbH, Hellersbergstrasse, Neuss, Germany
    Diabetes Obes Metab 11:786-94. 2009
    ..To investigate the safety, tolerability, pharmacokinetic and pharmacodynamic properties of multiple oral doses of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (BI 1356) in patients with type 2 diabetes mellitus...
  39. ncbi (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with oth
    Leo Thomas
    Boehringer Ingelheim Pharma GmbH and Co KG, Department of Metabolic Diseases Research, Birkendorfer Strasse 65, D 88397 Biberach, Germany
    J Pharmacol Exp Ther 325:175-82. 2008
    ..In conclusion, BI 1356 inhibited DPP-4 more effectively than vildagliptin, sitagliptin, saxagliptin, and alogliptin and has the potential to become the first truly once-a-day DPP-4 inhibitor for the treatment of type 2 diabetes...
  40. pmc Efficacy and safety of linagliptin in type 2 diabetes subjects at high risk for renal and cardiovascular disease: a pooled analysis of six phase III clinical trials
    Maximilian von Eynatten
    Boehringer Ingelheim Pharmaceuticals, 900 Ridgebury Road, P, O, Box 368, Ridgefield, CT 06877, USA
    Cardiovasc Diabetol 12:60. 2013
    ..This post hoc analysis of data from a global development program aimed to evaluate the efficacy and safety of linagliptin in a population with joint prevalence of these two vascular risk factors...
  41. pmc HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity
    Samer R Eid
    Department of Pain Research, Neuroscience Drug Discovery, Merck Research Laboratories, West Point, Philadelphia, USA
    Mol Pain 4:48. 2008
    ..The current study was designed to further explore the therapeutic potential of pharmacological TRPA1 antagonism to treat inflammatory and neuropathic pain...
  42. ncbi Effects of sildenafil on oxidative and inflammatory injuries of the kidney in streptozotocin-induced diabetic rats
    Kyung Hwan Jeong
    Department of Nephrology, School of Medicine, Kyung Hee University, Seoul, Korea
    Am J Nephrol 29:274-82. 2009
    ..Because sildenafil citrate (Viagra) has variable cardiovascular benefits, including antioxidative and immunomodulating effects, we investigated its influence on oxidative stress and inflammation in diabetic rat kidney...
  43. pmc Elevated airway purines in COPD
    Charles R Esther
    Department of Pediatric Pulmonology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Chest 140:954-60. 2011
    Adenosine and related purines have established roles in inflammation, and elevated airway concentrations are predicted in patients with COPD...
  44. ncbi Inhibition of phosphodiesterase-5 rescues age-related impairment of synaptic plasticity and memory
    Agostino Palmeri
    Department of Bio Medical Sciences Section of Physiology, University of Catania, Catania, 95125, Italy
    Behav Brain Res 240:11-20. 2013
    ..Our data suggest that inhibition of phosphodiesterase-5 may be beneficial to treat age-related cognitive dysfunction in a physiological mouse model of aging...
  45. ncbi The DPP4 inhibitor linagliptin delays the onset of diabetes and preserves β-cell mass in non-obese diabetic mice
    Jacob Jelsing
    Gubra ApS, Agern Alle 1, 2970 Hørsholm, Denmark
    J Endocrinol 214:381-7. 2012
    ..The data indicate that linagliptin treatment delays the onset of diabetes in NOD mice by protecting β-cell mass...
  46. pmc HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans
    Sachie Marubayashi
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    J Clin Invest 120:3578-93. 2010
    ..Importantly, PU-H71 treatment also reduced the mutant allele burden in mice. These data establish what we believe to be a novel therapeutic rationale for HSP90 inhibition in the treatment of JAK2-dependent MPN...
  47. pmc CR8, a selective and potent CDK inhibitor, provides neuroprotection in experimental traumatic brain injury
    Shruti V Kabadi
    Department of Anesthesiology, Center for Shock, Trauma, and Anesthesiology Research STAR, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Neurotherapeutics 9:405-21. 2012
    ..Given the increased potency and efficacy of CR8 as compared to earlier purine analog types of CDK inhibitors, this drug should be considered as a candidate for future clinical trials of TBI...
  48. ncbi The novel DPP-4 inhibitors linagliptin and BI 14361 reduce infarct size after myocardial ischemia/reperfusion in rats
    Berthold Hocher
    Institute of Nutritional Science, University of Potsdam, Potsdam, Germany
    Int J Cardiol 167:87-93. 2013
    ..This study evaluated the novel xanthine-based dipeptidylpeptidase-4 inhibitors linagliptin (BI 1356) and BI 14361 in cardiac ischemia...
  49. pmc Nutrient transport and pathogenesis in selected parasitic protozoa
    Scott M Landfear
    Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA
    Eukaryot Cell 10:483-93. 2011
    ..Permeases reviewed include those for hexoses, purines, iron, polyamines, carboxylates, and amino acids...
  50. ncbi Completing the purine utilisation pathway of Aspergillus nidulans
    Christos Gournas
    Faculty of Biology, Panepistemioupolis 15781, Athens, Greece
    Fungal Genet Biol 48:840-8. 2011
    ..The identification of these additional genes confirms the complete absence of clustering of the genes involved in purine utilisation in A. nidulans...
  51. ncbi Long-term continuous sildenafil treatment ameliorates corporal veno-occlusive dysfunction (CVOD) induced by cavernosal nerve resection in rats
    I Kovanecz
    LA Biomedical Research Institute at Harbor UCLA Medical Center, Urology Research Laboratory, Torrance, CA 90502 2064, USA
    Int J Impot Res 20:202-12. 2008
    ....
  52. ncbi Effect of sildenafil on the anticonvulsant action of classical and second-generation antiepileptic drugs in maximal electroshock-induced seizures in mice
    Dorota Nieoczym
    Department of Animal Physiology, Institute of Biology, Maria Curie Skłodowska University, Lublin, Poland
    Epilepsia 51:1552-9. 2010
    ....
  53. pmc Cdk2 is required for breast cancer mediated by the low-molecular-weight isoform of cyclin E
    Said Akli
    Department of Experimental Radiation Oncology, University of Texas, MD Anderson Cancer Center, TX, USA
    Cancer Res 71:3377-86. 2011
    ..Our findings establish a requirement for Cdk2 in LMW-cyclin E-mediated mammary tumorigenesis, arguing that human breast tumors overexpressing LMW-cyclin E are prime candidates for anti-Cdk2 therapy...
  54. ncbi cGMP modulates stem cells differentiation to neurons in brain in vivo
    U Gomez-Pinedo
    Laboratorio de Morfologia Celular, Centro de Investigacion Principe Felipe, Avda Autopista del Saler, Valencia, Spain
    Neuroscience 165:1275-83. 2010
    ..These results support that cGMP modulates the fate of neural stem cells in brain in vivo and suggest that high cGMP levels promote its differentiation to neurons while reduced cGMP levels promote differentiation to non-neuronal cells...
  55. ncbi Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes
    Carolyn F Deacon
    University of Copenhagen, Panum Institute, Department of Biomedical Sciences, DK 2200 Copenhagen N, Denmark
    Expert Opin Investig Drugs 19:133-40. 2010
    ..Type 2 diabetes is a progressive disease for which current treatments are often unsatisfactory with respect to achieving therapeutic goals and unwanted side effects...
  56. ncbi Prevalence of erectile dysfunction among Chinese men with type 2 diabetes mellitus
    G Yang
    Department of Endocrinology, Chinese PLA General Hospital, Beijing, China
    Int J Impot Res 22:310-7. 2010
    ..ED is a common complication in Chinese men with type 2 diabetes mellitus, and certain risk factors are associated with the presence of ED and severity. Sildenafil citrate is a safe and effective treatment for these patients...
  57. pmc Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity
    Roberto F Machado
    University of Illinois, Chicago, IL, USA
    Blood 118:855-64. 2011
    ..703), TRV (P = .503), or N-terminal pro-brain natriuretic peptide (P = .410). Sildenafil appeared to increase hospitalization rates for pain in patients with SCD. This study is registered at www.clinicaltrials.gov as NCT00492531...
  58. ncbi In vitro and in vivo pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine and CYC202
    Florence I Raynaud
    Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, Haddow Laboratories, Belmont, Sutton, United Kingdom
    Clin Cancer Res 11:4875-87. 2005
    ..To investigate pharmacokinetic-pharmacodynamic relationships for the trisubstituted aminopurine cyclin-dependent kinase inhibitors olomoucine, bohemine, and CYC202 (R-roscovitine; seliciclib) in the HCT116 human colon carcinoma model...
  59. pmc Distinct perturbation of the translatome by the antidiabetic drug metformin
    Ola Larsson
    Department of Oncology Pathology, Karolinska Institute, Stockholm 171 76, Sweden
    Proc Natl Acad Sci U S A 109:8977-82. 2012
    ..Thus, metformin selectively inhibits translation of mRNAs encoding proteins that promote neoplastic proliferation, which should facilitate studies on metformin and related biguanides in cancer prevention and treatment...
  60. ncbi Sildenafil-mediated neovascularization and protection against myocardial ischaemia reperfusion injury in rats: role of VEGF/angiopoietin-1
    Srikanth Koneru
    Department of Surgery, Molecular Cardiology and Angiogenesis Laboratory, University of Connecticut Health Center, Farmington, CT 06030 1110, USA
    J Cell Mol Med 12:2651-64. 2008
    ....
  61. ncbi The design, synthesis, and biological evaluation of novel substituted purines as HIV-1 Tat-TAR inhibitors
    Dekai Yuan
    National Research Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100083, PR China
    Bioorg Med Chem 15:265-72. 2007
    A series of novel substituted purines containing a side chain with a terminal amino or guanidyl group were designed and synthesized as HIV-1 Tat-TAR inhibitors...
  62. ncbi Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension
    Gerhard Paul Diller
    Adult Congenital Heart Centre and Centre for Pulmonary Hypertension, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK
    Circulation 117:3020-30. 2008
    ..We speculated that PAH patients are deficient in circulating endothelial progenitor cells (EPCs), potentially contributing to endothelial dysfunction and disease progression...
  63. ncbi Seliciclib (CYC202, R-roscovitine) enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft model
    Maria Virginia C L Appleyard
    Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom
    Int J Cancer 124:465-72. 2009
    ..In conclusion, the CDK inhibitor seliciclib (R-roscovitine) enhances the antitumor effect of doxorubicin in MCF7 tumors without increased toxicity with a mechanism that involves cell cycle arrest rather than apoptosis...
  64. ncbi Sildenafil prevents endothelial dysfunction induced by ischemia and reperfusion via opening of adenosine triphosphate-sensitive potassium channels: a human in vivo study
    Tommaso Gori
    Department of Internal, Cardiovascular, and Geriatric Medicine, Azienda Universitaria Ospedaliera Senese, Siena, Italy
    Circulation 111:742-6. 2005
    ..No study has investigated whether sildenafil can also prevent the impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) in humans...
  65. ncbi A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension
    Robyn J Barst
    Columbia University, New York, NY, USA
    Circulation 125:324-34. 2012
    ..Safe, effective therapy is needed for pediatric pulmonary arterial hypertension...
  66. ncbi Cloning, heterologous expression, and in situ characterization of the first high affinity nucleobase transporter from a protozoan
    Richard J S Burchmore
    Institute of Biomedical and Life Sciences, Division of Infection and Immunity, University of Glasgow, Glasgow G12 8QQ, United Kingdom
    J Biol Chem 278:23502-7. 2003
    ..Expression of TbNBT1 in Xenopus oocytes further confirmed that this gene encodes the first high affinity nucleobase transporter from protozoa or animals to be identified at the molecular level...
  67. ncbi Regadenoson: a new myocardial stress agent
    Wael Al Jaroudi
    Department of Medicine, The University of Alabama at Birmingham, USA
    J Am Coll Cardiol 54:1123-30. 2009
    ..This review will summarize the pre-clinical and clinical data on regadenoson, as they specifically relate to its use as a vasodilator stress agent, currently the only approved selective A(2A) agonist...
  68. ncbi Comparative profile of vasodilation by CVT-3146, a novel A2A receptor agonist, and adenosine in conscious dogs
    Gong Zhao
    CV Therapeutics, Inc, Palo Alto, CA 94304, USA
    J Pharmacol Exp Ther 307:182-9. 2003
    ..Furthermore, CVT-3146 did not cause renal vasoconstriction. These features make CVT-3146 a better candidate for pharmacologic stress testing...
  69. ncbi Sildenafil increases endothelial progenitor cell function and improves ischemia-induced neovascularization in hypercholesterolemic apolipoprotein E-deficient mice
    Sylvie Dussault
    Department of Cardiovascular Research, Centre Hospitalier de l Universite de Montreal, Montreal, Quebec, Canada
    Hypertension 54:1043-9. 2009
    ..Sildenafil could constitute a novel therapeutic strategy to reduce tissue ischemia in atherosclerotic diseases...
  70. ncbi Selective A2A adenosine receptor agonist as a coronary vasodilator in conscious dogs: potential for use in myocardial perfusion imaging
    Jean Noel Trochu
    Department of Physiology, New York Medical College, Valhalla, New York 10595, USA
    J Cardiovasc Pharmacol 41:132-9. 2003
    ....
  71. ncbi Estimating a minimally important difference in pulmonary arterial hypertension following treatment with sildenafil
    Claire Gilbert
    PGRD, Pfizer Ltd, Sandwich, UK
    Chest 135:137-42. 2009
    ..These analyses were undertaken to help define a minimally important difference (MID) in exercise capacity, measured by the 6-min walk distance (6MWD), and HRQoL, measured by the Short Form-36 (SF-36) questionnaire in patients with PAH...
  72. ncbi Uric acid and evolution
    Bonifacio Álvarez-Lario
    Department of Rheumatology, Complejo Asistencial de Burgos, Burgos, Spain
    Rheumatology (Oxford) 49:2010-5. 2010
    ..These hypotheses are discussed from an evolutionary perspective and their clinical significance. UA has some obvious harmful effects, and some, not so well-known, beneficial effects as an antioxidant and neuroprotector...
  73. ncbi Phase I evaluation of seliciclib (R-roscovitine), a novel oral cyclin-dependent kinase inhibitor, in patients with advanced malignancies
    Christophe Le Tourneau
    Department of Medical Oncology, Beaujon University Hospital, Paris 7, AP HP, Clichy, France
    Eur J Cancer 46:3243-50. 2010
    ..Phase I study of seliciclib (CYC202, R-roscovitine), an inhibitor of cyclin-dependent kinases 2, 7 and 9, causing cell cycle changes and apoptosis in cancer cells...
  74. pmc Cyclin-dependent kinase 5 regulates endothelial cell migration and angiogenesis
    Johanna Liebl
    Center for Drug Research, Pharmaceutical Biology, Ludwig Maximilians University, 81377 Munich, Germany
    J Biol Chem 285:35932-43. 2010
    ..It suggests Cdk5 as a novel, pharmacologically accessible target for antiangiogenic therapy and provides the basis for a new therapeutic application of Cdk5 inhibitors as antiangiogenic agents...
  75. ncbi Functional recovery in aged and young rats after embolic stroke: treatment with a phosphodiesterase type 5 inhibitor
    Li Zhang
    Department of Neurology, Henry Ford Health Sciences Center, Detroit, Mich, USA
    Stroke 36:847-52. 2005
    ..Here, we test the hypothesis that sildenafil provides restorative therapeutic benefit to the aged animal...
  76. ncbi Role of the cell cycle in the pathobiology of central nervous system trauma
    Ibolja Cernak
    Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA
    Cell Cycle 4:1286-93. 2005
    ....
  77. ncbi Novel short-acting A2A adenosine receptor agonists for coronary vasodilation: inverse relationship between affinity and duration of action of A2A agonists
    Z Gao
    Department of Pharmacological Sciences, CV Therapeutics, Palo Alto, California 94304, USA
    J Pharmacol Exp Ther 298:209-18. 2001
    ..Hence, the low-affinity A2A agonists CVT-3146 and CVT-3033 may prove to be superior to currently available high-affinity agonists as coronary vasodilators during myocardial imaging with radionuclide agents...
  78. ncbi Activation of the PI3-K/Akt pathway mediates cGMP enhanced-neurogenesis in the adult progenitor cells derived from the subventricular zone
    Lei Wang
    Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA
    J Cereb Blood Flow Metab 25:1150-8. 2005
    ..Furthermore, LY 294002 blocked Sildenafil-increased SVZ cell proliferation. These data suggest that Sildenafil-enhanced neurogenesis likely occurs through activation of the PI3-K/Akt/GSK-3 pathway...
  79. ncbi Chronic administration of Sildenafil improves markers of endothelial function in men with Type 2 diabetes
    A Aversa
    Department of Medical Pathophysiology, Sapienza University of Rome, Rome, Italy
    Diabet Med 25:37-44. 2008
    ..The aim of this study was to determine the effects of chronic therapy with sildenafil on endothelial function in patients with Type 2 diabetes mellitus (DM2)...
  80. ncbi Versatile effects of sildenafil: recent pharmacological applications
    Subramaniam Uthayathas
    Division of Pharmacology and Toxicology, Depertment of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA
    Pharmacol Rep 59:150-63. 2007
    ..The present review primarily focuses on the various pharmacological effects of sildenafil with regard to its influence on the nervous and pulmonary system...
  81. pmc Low-molecular-weight cyclin E can bypass letrozole-induced G1 arrest in human breast cancer cells and tumors
    Said Akli
    Departments of Experimental Radiation Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 16:1179-90. 2010
    ....
  82. pmc Microtubule-assisted mechanism for functional metabolic macromolecular complex formation
    Songon An
    Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA
    Proc Natl Acad Sci U S A 107:12872-6. 2010
    ..Collectively, we propose a microtubule-assisted mechanism for functional purinosome formation in HeLa cells...
  83. ncbi 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...
  84. pmc Improvement of vascular function by acute and chronic treatment with the PDE-5 inhibitor sildenafil in experimental diabetes mellitus
    A Schafer
    Medizinische Klinik und Poliklinik I, Universitatsklinikum Wurzburg, Julius Maximilians Universitat Wurzburg, Wurzburg, Bavaria, Germany
    Br J Pharmacol 153:886-93. 2008
    ..Diabetes-associated vascular dysfunction contributes to increased cardiovascular risk. We investigated whether the phosphodiesterase-5 inhibitor sildenafil would improve vascular function in diabetic rats...
  85. pmc Functional characterization of intracellular Dictyostelium discoideum P2X receptors
    Melanie J Ludlow
    Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, United Kingdom
    J Biol Chem 284:35227-39. 2009
    ..Responses to the calmodulin antagonist calmidazolium, however, were reduced in p2xA/B/C/D/E null cells suggesting that dP2X receptors play a role in intracellular calcium signaling...
  86. ncbi Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells
    John Wharton
    Section on Experimental Medicine and Toxicology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 ONN, UK
    Am J Respir Crit Care Med 172:105-13. 2005
    ..Phosphodiesterase Type 5 (PDE5) inhibition represents a novel strategy for the treatment of pulmonary hypertension...
  87. ncbi Cardiac phosphodiesterase 5 (cGMP-specific) modulates beta-adrenergic signaling in vivo and is down-regulated in heart failure
    H Senzaki
    Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA
    FASEB J 15:1718-26. 2001
    ....
  88. ncbi Hemodynamic and gas exchange effects of sildenafil in patients with chronic obstructive pulmonary disease and pulmonary hypertension
    Isabel Blanco
    Department of Pulmonary Medicine, Hospital Clinic Institut d Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona
    Am J Respir Crit Care Med 181:270-8. 2010
    ..However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition...
  89. pmc A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days
    C Benson
    Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey, UK
    Br J Cancer 96:29-37. 2007
    ..No objective tumour responses were noted, but disease stabilisation was recorded in eight patients; this lasted for a total of six courses (18 weeks) in a patient with ovarian cancer...
  90. ncbi Regadenoson induces comparable left ventricular perfusion defects as adenosine: a quantitative analysis from the ADVANCE MPI 2 trial
    John J Mahmarian
    Methodist DeBakey Heart and Vascular Center, Houston, Texas 77030, USA
    JACC Cardiovasc Imaging 2:959-68. 2009
    ..This study sought to determine whether regadenoson induces left ventricular perfusion defects of similar size and severity as seen with adenosine stress...
  91. pmc Cyclin-dependent kinase activity is required at early times for accurate processing and accumulation of the human cytomegalovirus UL122-123 and UL37 immediate-early transcripts and at later times for virus production
    Veronica Sanchez
    Molecular Biology Section, Mail Code 0366, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0366, USA
    J Virol 78:11219-32. 2004
    ..These results underscore the importance of accurate RNA processing and reiterate the significant role of cell cycle-regulatory factors in HCMV infection...
  92. ncbi Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-kappaB pathways
    Anwesha Dey
    Laboratory of Cell Cycle Control, Institute of Molecular and Cell Biology, Proteos, 138673 Singapore
    Nat Rev Drug Discov 7:1031-40. 2008
    ..In this Review we describe the principles behind such dual activities, describe the current candidate molecules and suggest mechanisms and approaches to their further development...
  93. ncbi Cyclin-dependent kinase inhibitor Roscovitine induces apoptosis in chronic lymphocytic leukemia cells
    I N Hahntow
    Department of Medicine, Technical University of Munich, Munich, Germany
    Leukemia 18:747-55. 2004
    ..Given its powerful effects on zap-70-positive and -negative B-CLL cells, but not on normal lymphocytes, Roscovitine might be an attractive drug to be tested in this incurable disease...
  94. ncbi Concentration-dependent plasma protein binding of the novel dipeptidyl peptidase 4 inhibitor BI 1356 due to saturable binding to its target in plasma of mice, rats and humans
    Holger Fuchs
    Department of Pharmacokinetics and Drug Metabolism, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach Riss, Germany
    J Pharm Pharmacol 61:55-62. 2009
    ..The purpose of this study was to characterise the plasma protein binding of BI 1356...
  95. pmc Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice
    Eiki Takimoto
    Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Clin Invest 119:408-20. 2009
    ..Thus, RGS2 is required for early myocardial compensation to pressure overload and mediates the initial antihypertrophic and cardioprotective effects of PDE5 inhibitors...
  96. ncbi Dual targeting of endothelial cells and pericytes in antivascular therapy for ovarian carcinoma
    Chunhua Lu
    Department of Gynecologic Oncology, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 13:4209-17. 2007
    ..Pericytes are known to provide a survival advantage for endothelial cells. We hypothesize that strategies aimed at dual targeting of tumor-associated endothelial cells and pericytes will be highly efficacious...
  97. ncbi Long-lasting arrest of murine polycystic kidney disease with CDK inhibitor roscovitine
    Nikolay O Bukanov
    Cell Biology, Genzyme Corporation, 5 Mountain Road, Framingham, Massachusetts 01701 9322, USA
    Nature 444:949-52. 2006
    ..Our results indicate that inhibition of CDK is a new and effective approach to the treatment of PKD...
  98. ncbi Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling
    Anindita Das
    Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298 0281, USA
    J Biol Chem 280:12944-55. 2005
    ..The results may have possible therapeutic potential in preventing myocyte cell death following ischemia/reperfusion...
  99. ncbi Safety of regadenoson, a selective adenosine A2A agonist, in patients with chronic obstructive pulmonary disease: A randomized, double-blind, placebo-controlled trial (RegCOPD trial)
    Gregory S Thomas
    Cardiology Division, University of California, Irvine, Irvine, USA
    J Nucl Cardiol 15:319-28. 2008
    ..Patients with reactive airways are at risk for adenosine-induced bronchoconstriction, mediated via A(2B) and/or A(3) adenosine receptors...
  100. ncbi Purine and pyrimidine metabolism in Leishmania
    Nicola S Carter
    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, Oregon 97239 3098, USA
    Adv Exp Med Biol 625:141-54. 2008
    b>Purines and pyrimidines are indispensable to all life, performing many vital functions for cells: ATP serves as the universal currency of cellular energy, cAMP and cGMP are key second messenger molecules, purine and pyrimidine ..
  101. ncbi Effect of sildenafil citrate and a nitric oxide donating sildenafil derivative, NCX 911, on cavernosal relaxation and superoxide formation in hypercholesterolaemic rabbits
    Nilima Shukla
    Bristol Heart Institute, Department of Cardiac Surgery, Bristol Royal Infirmary, Bristol BS2 8HW, UK
    Eur J Pharmacol 517:224-31. 2005
    ..It also indicates that NO donating sildenafil may be therapeutically more beneficial than conventional sildenafil in treating erectile dysfunction with an oxidative stress-related aetiology...

Research Grants64

  1. MECHANISM-BASED DRUG SELECTION AND DESIGN: NUCLEOTIDE SA
    Buddy Ullman; Fiscal Year: 2003
    ..despite the fact that (i) all of these pathogens are purine auxotrophs, (ii) the existing precedent of subversive purines as effective treatment for other parasitic diseases, and (iii) that the availability of antiparasitic lead ..
  2. Regulation of IFN-beta induction by P2X7 purinergic receptor signaling
    JUDITH ANNE SMITH; Fiscal Year: 2011
    ..My research proposes to study how substances that are released by tissue damage called "purines" regulate the production of the inflammatory cytokine IFN- [unreadable] by macrophages...
  3. DNA REPAIR IN A HORMONE RESPONSIVE GENE
    Michael J Smerdon; Fiscal Year: 2013
    ..NER of UV damage (CPDs) and BER of N-methyl purines (NMPs) will also be examined in well- characterized chromatin loci in the yeast S. cerevisiae...
  4. Regulations of DNA Alkylation/Deamination Damage Repair
    Rabindra Roy; Fiscal Year: 2013
    ..Among these, a series of structurally diverse damaged purines are repaired by N- methylpurine DNA-glycosylase (MPG), present in all species from bacteria to man...
  5. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2010
    ..This enzyme maintains tetrahydrofolate levels required to support the biosynthesis of purines, pyrimidines, and amino acids...
  6. Regulation of guanylyl cyclase A and B by hormones, ATP and phosphorylation
    Lincoln Ross Potter; Fiscal Year: 2013
    ..The first aim will measure the effects of structurally unique and reactive purines on the kinetic properties and binding sites of GC-A and GC-B...
  7. DEPOLARIZATION-SECRETION COUPLING IN NERVE TERMINALS
    Jose R Lemos; Fiscal Year: 2012
    ..OT. ATP is co-released with the HNS peptides. Purines, such as ATP and adenosine, interact with specific receptors on neurons, leading to a variety of effects...
  8. Intra- and Extra-Chromosomal Probes for Mutagenesis by Carcinogens
    John M Essigmann; Fiscal Year: 2013
    ..oligonucleotides containing 5-substituted cytosines (produced by oxidative stress), a series of N and 0-alkylated purines and pyrimidines (produced by alkylation and inflammation), and N2 and C8-purine aromatic amine adducts (produed ..
  9. Purine Salvage Pathway of Cryptosporidium Parvum
    Buddy Ullman; Fiscal Year: 2012
    ..parvum and its human host are the pathways for purine acquisition. C. parvum, unlike mammals, cannot synthesize purines de novo and is dependent upon a unique purine salvage mechanism to fulfill its nutritional needs...
  10. Genetic Analysis of Purine Metabolism in Leishmania donovani
    Buddy Ullman; Fiscal Year: 2013
    ..L. donovani, unlike the mammalian host, cannot synthesize purines de novo and consequently accommodates unique purine acquisition mechanisms to fulfill its nutritional needs...
  11. Gene-Nutrient Interactions in Neural Tube Defects
    Patrick J Stover; Fiscal Year: 2012
    Folate metabolism is required for the synthesis of nucleotides (purines and dTMP) and S- adenosylmethionine (AdoMet)...
  12. Pursuing purine pathways to clinical trials for Parkinson's disease
    Michael A Schwarzschild; Fiscal Year: 2012
    ..and laboratory models of PD, the PI and his colleagues have obtained convergent evidence that two ubiquitous purines might reduce the risk of developing PD: caffeine (an adenosine receptor antagonist) and urate (the end product of ..
  13. Structural Biology of Purine and Pyrimidine Biosynthesis and Metabolism
    Steven E Ealick; Fiscal Year: 2012
    ..Catabolic pathways for the degradation of purines and pyrimidines have been previously described and structures are available for the key enzymes;however, recently ..
  14. Identification of post-transcriptionally regulated targets by TrIP-Chip/Seq
    Jingfang Ju; Fiscal Year: 2013
    ..DHFR plays a critical role in folate homeostasis, and is required for the de novo synthesis of purines, thymidylate and certain amino acids. Therefore, DHFR has served as a critical target in cancer chemotherapy...
  15. Purine Nucleoside/Nucleobase Transporters in Leishmania
    Scott Landfear; Fiscal Year: 2013
    ..All parasitic protozoa examined to date are unable to synthesize purines and must salvage these essential nutrients from their hosts...
  16. Role of urate in protecting mitochondrial function in the brain
    David K Simon; Fiscal Year: 2013
    ..mitochondrial dysfunction in the CNS with another lab characterizing the neuroprotective potential of purines like urate, the proposed exploratory project will test the central hypothesis that urate plays a crucial role in ..
  17. Postsynaptic Activity of Type II Cochlear Afferents
    CATHERINE JEANNE CHALENSKI WEISZ; Fiscal Year: 2010
    ..b>Purines stimulate the Type II afferents, both directly and by eliciting synaptic input from OHCs (preliminary data)...
  18. The Guanosine-Adenosine Mechanism
    EDWIN KERRY JACKSON; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Adenosine and guanosine are naturally-occurring and structurally similar purines. Moreover, naturally- occurring cyclic analogues of adenosine and guanosine are involved in similar physiological ..
  19. Purines as Biomarkers of Respiratory Disease
    CHARLES RICHARD ESTHER; Fiscal Year: 2013
    ..Development of these methods will provide invaluable tools for clinical management and research in cystic fibrosis and other lung diseases. ..
  20. Structure/function studies of nucleoside analog activating enzymes
    Arnon Lavie; Fiscal Year: 2009
    ..This inherent promiscuity also enables NAs of various structures (e.g. purines, pyrimidines, with modifications in the sugar, base, or both moieties) to be accepted as substrates...
  21. TRANSFORMYLASE ENZYMES DIHYDROFOLATE REDUCTASE
    Stephen J Benkovic; Fiscal Year: 2013
    ..by applicant): The de novo purine biosynthetic pathway generates inosine monophosphate, the precursor to purines and their derivatives that act in numerous cellular anabolic and catabolic networks...
  22. Corneal epithelial adhesion:morphology and biochemistry
    VICKERY E TRINKAUS-RANDALL; Fiscal Year: 2012
    ..Our lab has demonstrated that the active components that are released upon injury are purines and pyrimidines (nucleotides), which cause the propagation of a Ca2+ wave to neighboring cells...
  23. Hoogsteen base pairing in human DNA polymerase iota
    Satya Prakash; Fiscal Year: 2010
    ..of adenine and guanine to analyze the contributions of different hydrogen bond acceptors/donors in template purines to their Hoogsteen pairing with the incoming pyrimidine nucleotide (nt)...
  24. IMP Dehydrogenase
    LIZBETH K HEDSTROM; Fiscal Year: 2013
    ..This reaction controls the entry of purines into the guanine nucleotide pool, which in turn controls proliferation, making IMPDH a billion-dollar target for ..
  25. Ribavirin depletes endogenous nucleotide pools
    JENNIFER JUSTICE KISER; Fiscal Year: 2013
    ..In vitro, ribavirin depletes endogenous purines which likely explains its toxic and therapeutic effects, but this has not been investigated in humans...
  26. Neuroimaging of Purinergic Pathways in the Human ENS
    FEDIAS LEONTIOU CHRISTOFI; Fiscal Year: 2013
    ..Our animal studies indicate that purines (ATP/ADP/ADO) operate at all levels of the reflex...
  27. Pulmonary Surface Liquid Homeostasis
    RICHARD CHARLES BOUCHER; Fiscal Year: 2013
    ..Focusing on CFTR, ENaC, and extracellular purines/purinoceptors, the PPG proposes to elucidate the molecular mechanisms that 1) regulate pulmonary surface liquid ..
  28. Purinergic Regulation of hepatocyte proliferation
    Sundararajah Thevananther; Fiscal Year: 2010
    ..via the activation of cell surface P2 purinergic receptors, and the mitogenic potential of extracellular purines are beginning to be recognized in many other cell types...
  29. Purines and the health of retinal ganglion cells
    Claire H Mitchell; Fiscal Year: 2012
    ..This proposal will confirm this relationship and explore how this pathological release occurs with the aim of preventing the initial stages of damage in glaucoma. ..
  30. MEMBRANE-LIMITED METABOLISM IN MAMMALIAN RED CELLS
    Hyun Kim; Fiscal Year: 1990
    The results support our working hypothesis that plasma purines present at micromolar concentrations play a significant metabolic role in red cell energetics...
  31. PURINE BOTTLENECKS FOR THE CHEMOTHERAPY OF TOXOPLASMOSIS
    ELMER PFEFFERKORN; Fiscal Year: 1999
    ..Toxoplasma gondii is absolutely dependent upon an exogenous source of preformed purines and usually obtains them from its host cell...
  32. MUTATIONAL ANALYSIS OF A PARASITE PURINE SALVAGE ENZYME
    SYDNEY CRAIG; Fiscal Year: 2001
    ..In contrast, most parasites are unable to synthesize purines via de novo pathways, and must rely on enzymes in salvage pathways, including HPRTs, for the purines needed in ..
  33. Biosynthesis of deazapurine-containing metabolites
    Vahe Bandarian; Fiscal Year: 2013
    ..Deazapurines are secondary metabolites that are derived from purines. This proposal outlines studies on the biosynthesis of deazapurine-containing secondary metabolites by bacteria...
  34. PHARMACOLOGY OF DIDEOXYNUCLEOSIDES IN SMALL INTESTINAL
    JESSIE AU; Fiscal Year: 1991
    ..Examine the effects of ddNS on the levels and metabolism of endogenous pyrimidines and purines (thymidine, deoxycytidine, deoxyinosine, deoxyadenosine and adenosine), and the incorporation of DNA precursor (..
  35. GENETIC EFFECTS-FOLATE-DEPENDENT ONE-CARBON METABOLISM
    JESSE GREGORY; Fiscal Year: 2004
    ..We also hypothesize that the rate of folate-dependent synthesis of nucleotides (purines and thymidylate) will be reduced in folate deficiency but may be enhanced by the C677T mutation...
  36. MOLECULAR MECHANISMS OF PRPP-SYNTHETASE OVERACTIVITY
    THOMAS PALELLA; Fiscal Year: 1990
    ..The formation of PRPP by this enzyme represents the first step in the de novo synthesis of purines, pyrimidines and pyridines...
  37. REGULATION OF MAMMALIAN OOCYTE DEVELOPMENT
    John Eppig; Fiscal Year: 1993
    ..1) Granulosa cells produce hypoxanthine and other purines that could participate in the maintenance of meiotic arrest...
  38. CRYSTAL STRUCTURE OF TOXOPLASMA GONDII HGPRT
    DAVID BORHANI; Fiscal Year: 1999
    ..Since T. gondii are incapable of de novo synthesis of purine nucleotides, but instead salvage host purines, the applicant's long term research goal is to use this crucial aspect of parasitic metabolism to advantage: They ..
  39. MOLECULAR MECHANISMS OF PRPP-SYNTHETASE OVERACTIVITY
    Blake Roessler; Fiscal Year: 1991
    ..The formation of PRPP by this enzyme represents the first step in the de novo synthesis of purines, pyrimidines and pyridines...
  40. ROLE OF ADENYL PURINES IN MYOMETRIAL FUNCTION
    IAIN BUXTON; Fiscal Year: 1993
    This project proposes that adenyl purines, compounds known to cause contraction of uterus, participate in the regulation of human parturition...
  41. DISRUPTION OF DNA FUNCTION BY TG INCORPORATION
    Jonathan Maybaum; Fiscal Year: 1990
    Many anticancer and antiviral agents are analogs of purines or pyrimidines that are thought to act by being incorporated into DNA...
  42. EXCRETED ALKYL PURINES AS MARKERS OF IN VIVO DNA DAMAGE
    David Shuker; Fiscal Year: 1990
    ..of the proposed work is to develop, validate and apply methods for the determination of excreted alkylated purines as markers of DNA alkylation in vivo in humans...
  43. PURINE-DOPAMINE RELATIONSHIPS IN LESCH-NYHAN DISEASE
    HYDER JINNAH; Fiscal Year: 2001
    ..Aim 2 addresses the possibility that a deficiency of brain purines during development may be responsible for abnormal dopamine neuron develop or function...
  44. Vaccine Development: Purinergic Agonists as Adjuvants
    Richard Granstein; Fiscal Year: 2005
    ..e. the cell surface receptors that respond to purines and related agonists), which are expressed on the surface of antigen presenting cells in the skin, can enhance ..
  45. LEISHMANIA DONOVANI SURFACE MEMBRANES: 3 NUCLEOTIDASE
    Michael Gottlieb; Fiscal Year: 1990
    ..donovani and in the insect trypanosomatid Crithidia luciliae is regulated by the supply of available purines in culture media, i.e...
  46. FOLIC ACID REQUIREMENTS AND ONE CARBON METABOLISM
    Barry Shane; Fiscal Year: 2004
    ..These reactions which include the metabolic cycles for the synthesis of thymidylate, purines and the amino acids, methionine, serine and glycine, are compartmentalized in the mitochondria and cytosol of ..
  47. BIOSYNTHESIS AND INTERCONVERSION OF PURINES
    JOSEPH GOTS; Fiscal Year: 1980
    ....
  48. NOVEL URACILS, PYRIMIDINES, AZOLES AND PURINES
    Harold Shechter; Fiscal Year: 1991
    ..polyazaazulenes and their analogs and (3) develop the chemistry of diazo-, azido- and diazomethylpyrimidines and purines, their carbenes and their nitrenes...
  49. Salvage Transporter as a Target for Drug Discovery
    Joanne Wang; Fiscal Year: 2004
    ..circumvent the growth-inhibitory effect of antipurine antimetabolites via the salvage of extracellular preformed purines such as hypoxanthine, nucleobase transporter's that mediate cellular uptake of purines represent a promising ..
  50. RADIAL AND LONGITUDINAL MICROVASCULAR COMMUNICATION
    Hans Dietrich; Fiscal Year: 2000
    ..The investigators found that extraluminally applied purines, including adenosine-triphosphate (ATP), caused a vasoconstriction in cerebral arterioles which surprisingly was ..
  51. TUMOR SENSITIZATION TO PURINE ANALOGS BY E.COLI PNP
    William Parker; Fiscal Year: 2004
    ..it from the other suicide gene therapy strategies (for example, high bystander activity, potency of the toxic purines generated, activity against non-proliferating tumor cells, potent anti-tumor effects after 1 dose of compound)...
  52. HYPOXIC PULMONARY VASOCANSTRICTION AND RED BLOOD CELLS
    Steven Deem; Fiscal Year: 2002
    ..In addition, the purines adenosine and adenosine triphosphate (ATP) may play a role in modulation of pulmonary vascular tone by RBCs...
  53. SOMATIC CELL GENETIC ANALYSIS OF PURINE SYNTHESIS
    David Patterson; Fiscal Year: 2001
    b>Purines are fundamental biological molecules. They are components of DNA and RNA, the genetic information of all living organisms...
  54. PURINERGIC REGULATION OF OCULAR CILIARY EPITHELIUM
    MORTIMER CIVAN; Fiscal Year: 2000
    ..This coordination may reflect synergistic effects of purines and an unidentified intracellular regulator, whose action is mimicked by tamoxifen...
  55. COMPARATIVE MODEL FOR IMMOBILITY OSTEOPENIA
    Paul Milbury; Fiscal Year: 1993
    ..g., tyrosine and tryptophan metabolites, neurotransmitters, cofactors, peptides and purines) can predict and precede or trigger changes in the balance of anabolic and catabolic processes ultimately ..
  56. VIBRATIONAL SPECTROSCOPY OF BIOCHEMICAL MOLECULES
    WILLIS PERSON; Fiscal Year: 1992
    ..Related to this will be a theoretical and experimental study of changes in the spectra as purines and pyrimidines from self-associated dimers, complexes with small probe molecules (H20, CO, HCl, etc...
  57. DEVELOPMENT OF NEW ANTITUMOR AGENTS
    William Parker; Fiscal Year: 2005
    ..and in-depth investigations of mechanism of action of new anticancer agents of the following classes: analogs of purines and pyrimidines and their nucleosides and nucleotides and analogs of penclomedine, a new agent evaluated in Phase ..
  58. ETHANOL RESULTS IN OXIDANT DEPENDENT TISSUE INJURY
    DALE PARKS; Fiscal Year: 2002
    ..integrate the effects of chronic ethanol consumption to the generation of reactive radical species, nitration of purines, proteins and lipids, and the consequent alterations in hepatic, pulmonary, and vascular structure/function...
  59. REGULATION OF CORONARY ARTERY FLOW BY ENDOTHELIAL CELLS
    Dennis Cheek; Fiscal Year: 2000
    ..The mediators to be examined are the adenyl purines (i.e., ATP, ADP, and adenosine)...
  60. SYNTHESIS OF 15N LABELED RNA FRAGMENTS
    Roger Jones; Fiscal Year: 2001
    ..utility of 15N specifically labeled nucleosides will be expanded by introducing 13C into the C8 position of both purines and the C2 position of adenine...
  61. Molecular Mechanisms of PDE5 Regulation
    Jackie Corbin; Fiscal Year: 2005
    ..Results of these studies will provide a basis for understanding fundamental questions relating to cGMP signaling in many tissues. ..
  62. CYCLIC AMP/ADENOSINE PATHWAY
    Edwin Jackson; Fiscal Year: 2002
    ..abstract_text> ..
  63. Molecular Control of cGMP Signaling by PKGs and PDEs
    Jackie Corbin; Fiscal Year: 2007
    ..A thorough physical and biochemical characterization of PDE11 will be carded out, and the likelihood of regulation of this enzyme by ligand binding to its GAF domains or by enzyme phosphorylation will be explored. ..
  64. The Efficacy of TUMT and Neoadjuvant Finasteride for BPH
    Kevin McVary; Fiscal Year: 2005
    ..We are proposing a 3-arm, placebo/sham controlled, randomized clinical trial using changes in symptoms as the primary ..