amidines

Summary

Top Publications

  1. pmc Conflict of interest: use of pyrethroids and amidines against tsetse and ticks in zoonotic sleeping sickness endemic areas of Uganda
    Kevin Bardosh
    Division of Pathway Medicine and Centre for Infectious Diseases, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Chancellor s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK
    Parasit Vectors 6:204. 2013
  2. ncbi 1400W is a slow, tight binding, and highly selective inhibitor of inducible nitric-oxide synthase in vitro and in vivo
    E P Garvey
    Institute of Biochemistry, Glaxo Wellcome, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 272:4959-63. 1997
  3. pmc Mechanisms underlying differences in systemic exposure of structurally similar active metabolites: comparison of two preclinical hepatic models
    Grace Zhixia Yan
    Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 7569, USA
    J Pharmacol Exp Ther 337:503-12. 2011
  4. ncbi Design and screening of ASIC inhibitors based on aromatic diamidines for combating neurological disorders
    Xuanmao Chen
    Department of Physiology, University of Toronto, Canada
    Eur J Pharmacol 648:15-23. 2010
  5. ncbi Free-radical-scavenging effect of carbazole derivatives on AAPH-induced hemolysis of human erythrocytes
    You Zhi Tang
    Department of Organic Chemistry, College of Chemistry, Jilin University, Changchun 130021, China
    Bioorg Med Chem 15:1903-13. 2007
  6. pmc Water-mediated binding of agents that target the DNA minor groove
    Yang Liu
    Department of Chemistry, Georgia State University, Atlanta, Georgia 30302 4098, USA
    J Am Chem Soc 133:10171-83. 2011
  7. ncbi Selective inhibition of inducible nitric oxide synthase inhibits tumor growth in vivo: studies with 1400W, a novel inhibitor
    L L Thomsen
    Glaxo Wellcome Research and Development, Medicines Research Centre, Ware, Hertfordshire, United Kingdom
    Cancer Res 57:3300-4. 1997
  8. pmc Protein arginine deiminase 4: a target for an epigenetic cancer therapy
    Jessica L Slack
    Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
    Cell Mol Life Sci 68:709-20. 2011
  9. ncbi Analysis of highly potent amidine containing inhibitors of serine proteases and their N-hydroxylated prodrugs (amidoximes)
    Joscha Kotthaus
    Department of Pharmaceutical and Medicinal Chemistry, Christian Albrechts University of Kiel, Kiel, Germany
    J Enzyme Inhib Med Chem 26:115-22. 2011
  10. pmc Characterization of C-alkyl amidines as bioavailable covalent reversible inhibitors of human DDAH-1
    Matthew Lluis
    Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, University of Texas, Austin, 78712 0165, USA
    ChemMedChem 6:81-8. 2011

Research Grants

Detail Information

Publications250 found, 100 shown here

  1. pmc Conflict of interest: use of pyrethroids and amidines against tsetse and ticks in zoonotic sleeping sickness endemic areas of Uganda
    Kevin Bardosh
    Division of Pathway Medicine and Centre for Infectious Diseases, School of Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Chancellor s Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK
    Parasit Vectors 6:204. 2013
    ..The private veterinary market is divided between products only effective against ticks (amidines) and those effective against both ticks and tsetse (pyrethroids)...
  2. ncbi 1400W is a slow, tight binding, and highly selective inhibitor of inducible nitric-oxide synthase in vitro and in vivo
    E P Garvey
    Institute of Biochemistry, Glaxo Wellcome, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 272:4959-63. 1997
    ..Thus, the potency and selectivity of 1400W inhibition of iNOS both in vitro and in vivo were far greater than of any previously described iNOS inhibitor...
  3. pmc Mechanisms underlying differences in systemic exposure of structurally similar active metabolites: comparison of two preclinical hepatic models
    Grace Zhixia Yan
    Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 7569, USA
    J Pharmacol Exp Ther 337:503-12. 2011
    ..A higher f(u,L) explained, in part, the enhanced perfusate AUC of CPD-0801 compared with furamidine in IPLs. SCH predicted the disposition of prodrug/metabolite in IPLs...
  4. ncbi Design and screening of ASIC inhibitors based on aromatic diamidines for combating neurological disorders
    Xuanmao Chen
    Department of Physiology, University of Toronto, Canada
    Eur J Pharmacol 648:15-23. 2010
    ..Further studies may lead to a drug with therapeutic value and extend the therapeutic scope of aromatic diamidines to combat neurological diseases...
  5. ncbi Free-radical-scavenging effect of carbazole derivatives on AAPH-induced hemolysis of human erythrocytes
    You Zhi Tang
    Department of Organic Chemistry, College of Chemistry, Jilin University, Changchun 130021, China
    Bioorg Med Chem 15:1903-13. 2007
    ..These findings may be useful for the development of agents for various ROS-mediated diseases in vivo...
  6. pmc Water-mediated binding of agents that target the DNA minor groove
    Yang Liu
    Department of Chemistry, Georgia State University, Atlanta, Georgia 30302 4098, USA
    J Am Chem Soc 133:10171-83. 2011
    ..DB921 has a benzimidazole-biphenyl system with terminal amidines that results in a linear conformation that does not possess the appropriate radius of curvature to match the ..
  7. ncbi Selective inhibition of inducible nitric oxide synthase inhibits tumor growth in vivo: studies with 1400W, a novel inhibitor
    L L Thomsen
    Glaxo Wellcome Research and Development, Medicines Research Centre, Ware, Hertfordshire, United Kingdom
    Cancer Res 57:3300-4. 1997
    ..These studies confirm that nitric oxide production in tumors plays a role in promoting their growth, rather than a role as a host defense mechanism in inhibiting growth...
  8. pmc Protein arginine deiminase 4: a target for an epigenetic cancer therapy
    Jessica L Slack
    Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
    Cell Mol Life Sci 68:709-20. 2011
    ..Taken together, these findings suggest PAD4 inhibition as a novel epigenetic approach for the treatment of cancer, and suggest that F- and Cl-amidine are candidate therapeutic agents for this disease...
  9. ncbi Analysis of highly potent amidine containing inhibitors of serine proteases and their N-hydroxylated prodrugs (amidoximes)
    Joscha Kotthaus
    Department of Pharmaceutical and Medicinal Chemistry, Christian Albrechts University of Kiel, Kiel, Germany
    J Enzyme Inhib Med Chem 26:115-22. 2011
    ..In order to improve oral bioavailability of these drugs, prodrug principles such as the conversion of amidines into amidoximes may be applied...
  10. pmc Characterization of C-alkyl amidines as bioavailable covalent reversible inhibitors of human DDAH-1
    Matthew Lluis
    Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, University of Texas, Austin, 78712 0165, USA
    ChemMedChem 6:81-8. 2011
    ..Using a two-part click-chemistry-mediated activity probe, a homologated series of C-alkyl amidines were ranked for their ability to inhibit DDAH-1 within cultured HEK 293T cells...
  11. ncbi Endotoxemia-mediated induction of cardiac inducible nitric-oxide synthase expression accounts for the hypotensive effect of ethanol in female rats
    Mahmoud M El-Mas
    Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27834, USA
    J Pharmacol Exp Ther 324:368-75. 2008
    ..These findings yield insight into the mechanistic role of endotoxin-myocardial iNOS signaling in the cardiodepressant action of ethanol, which accounts for its hypotensive effect in conscious female rats...
  12. ncbi Effect of polymer structure on micelles formed between siRNA and cationic block copolymer comprising thiols and amidines
    R James Christie
    Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Japan
    Biomacromolecules 12:3174-85. 2011
    ..b>Amidines formed with 2-IT were unstable and rearranged into a noncharged ring structure lacking free thiol functionality, ..
  13. ncbi Amidines, isothioureas, and guanidines as nucleophilic catalysts
    James E Taylor
    Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK
    Chem Soc Rev 41:2109-21. 2012
    ..b>Amidines and guanidines are often only thought of as strong organic bases however, a number of small molecules containing ..
  14. pmc Palladium-catalyzed N-monoarylation of amidines and a one-pot synthesis of quinazoline derivatives
    Meredeth A McGowan
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
    Org Lett 14:3800-3. 2012
    A method for the Pd-catalyzed N-arylation of both aryl and alkyl amidines with a wide range of aryl bromides, chlorides, and triflates is described...
  15. pmc Silver(I)-promoted conversion of thioamides to amidines: divergent synthesis of a key series of vancomycin aglycon residue 4 amidines that clarify binding behavior to model ligands
    Akinori Okano
    Department of Chemistry and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    J Am Chem Soc 134:8790-3. 2012
    Development of a general Ag(I)-promoted reaction for the conversion of thioamides to amidines is disclosed...
  16. pmc Direct palladium(II)-catalyzed synthesis of arylamidines from aryltrifluoroborates
    Jonas Sävmarker
    Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry BMC, Uppsala University, Box 574, SE 751 23, Uppsala, Sweden
    Org Lett 14:2394-7. 2012
    ..The coupling was achieved by Pd(II)-catalysis in a one step 20 min microwave protocol using Pd(O(2)CCF(3)), 6-methyl-2,2'-bipyridyl, TFA, and MeOH, providing the corresponding arylamidines in moderate to excellent yields...
  17. ncbi In vitro and in vivo pharmacological characterization of BIIL 284, a novel and potent leukotriene B(4) receptor antagonist
    F W Birke
    Department of Pulmonary Research, Boehringer Ingelheim Pharma, KG D 55216 Ingelheim am Rhein, Germany
    J Pharmacol Exp Ther 297:458-66. 2001
    ..BIIL 284 is an unusually potent and long-acting orally active LTB(4) antagonist, and is therefore under clinical development as a novel anti-inflammatory principle...
  18. pmc In vitro and in vivo antimalarial activities of T-2307, a novel arylamidine
    Akiko Kimura
    Research Laboratories, Toyama Chemical Co, Ltd, Toyama, Japan
    Antimicrob Agents Chemother 56:2191-3. 2012
    ..17 μM, respectively. T-2307 at 2.5 to 10 mg/kg of body weight/day exhibited activity against blood stage and liver stage parasites in rodent malaria models. In conclusion, T-2307 exhibited in vitro and in vivo antimalarial activity...
  19. pmc Novel amidines and analogues as promising agents against intracellular parasites: a systematic review
    M N C Soeiro
    Laboratόrio de Biologia Celular, Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil
    Parasitology 140:929-51. 2013
    ..This review summarizes the knowledge on amidines and analogues with respect to their synthesis, pharmacological profile, mechanistic and biological effects upon a ..
  20. pmc A cellular model for screening neuronal nitric oxide synthase inhibitors
    Jianguo Fang
    Department of Chemistry, Northwestern University, Evanston, Il 60208 3113, USA
    Anal Biochem 390:74-8. 2009
    ..The cell-based assay provides more information than in vitro assays regarding the bioavailability of NOS inhibitors, and it is suitable for high-throughput screening...
  21. ncbi Structure-activity relationship of novel and known inhibitors of human dimethylarginine dimethylaminohydrolase-1: alkenyl-amidines as new leads
    Jürke Kotthaus
    Department of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Christian Albrechts University of Kiel, Gutenbergstrasse 76 78, D 24118 Kiel, Germany
    Bioorg Med Chem 16:10205-9. 2008
    ..the binding pocket of the guanidine-moiety was investigated by screening differently substituted guanidines, amidines and isothioureas in order to collect information on possible binding modes in the active site...
  22. pmc PP2B-dependent NO production in the medullary thick ascending limb during diabetes
    Jan M Foster
    Vascular Biology Center, Medical College of Georgia, Augusta, Georgia 30912, USA
    Am J Physiol Renal Physiol 297:F471-80. 2009
    ..In conclusion, while NO bioavailability in mTALs is reduced during diabetes, free radical scavenging with tempol unmasks increased NO production that involves PP2B-dependent activation of NOS1 and NOS2...
  23. ncbi Rapid synthesis of 1,3,5-substituted 1,2,4-triazoles from carboxylic acids, amidines, and hydrazines
    Georgette M Castanedo
    Discovery Chemistry Group, Genentech, Inc, 1 DNA Way, South San Francisco, California 94080, USA
    J Org Chem 76:1177-9. 2011
    ..synthesis of 1,3,5-trisubstituted 1,2,4-triazoles has been developed from reaction of carboxylic acids, primary amidines, and monosubstituted hydrazines...
  24. pmc N-allyl-N-sulfonyl ynamides as synthetic precursors to amidines and vinylogous amidines. An unexpected N-to-C 1,3-sulfonyl shift in nitrile synthesis
    Kyle A Dekorver
    Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53705, USA
    J Org Chem 76:5092-103. 2011
    ..Collectively, this work showcases the rich array of chemistry one can discover using these ynamides...
  25. ncbi Insertion of arynes into thioureas: a new amidine synthesis
    Kallolmay Biswas
    School of Chemistry, University of Edinburgh, Joseph Black Building, King s Buildings, West Mains Rd, Edinburgh EH9 3JJ, UK
    Org Lett 13:4946-9. 2011
    ..The reaction contrasts with that of ureas, which proceeds via benzyne σ-insertion into the C-N bond, and represents a new, operationally simple route to functionalized amidines.
  26. ncbi Synthesis of quinazolin-4(3H)-ones via Pd(II)-catalyzed intramolecular C(sp2)-H carboxamidation of N-arylamidines
    Bin Ma
    State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, China
    J Org Chem 76:6362-6. 2011
    ..Compared with existing approaches to quinazolin-4(3H)-ones, the current strategy features atom-economy and step-efficiency...
  27. pmc Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization
    Yuan Luo
    Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, South Carolina 29208, USA
    Biochemistry 45:11727-36. 2006
    ..In addition, they represent potential lead compounds for the treatment of rheumatoid arthritis because a growing body of evidence supports a role for PAD4 in the onset and progression of this chronic autoimmune disorder...
  28. pmc Novel arylimidamides for treatment of visceral leishmaniasis
    Michael Zhuo Wang
    Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Antimicrob Agents Chemother 54:2507-16. 2010
    ....
  29. ncbi Inactivation of two diverse enzymes in the amidinotransferase superfamily by 2-chloroacetamidine: dimethylargininase and peptidylarginine deiminase
    Everett M Stone
    Graduate Program in Cell and Molecular Biology, The University of Texas, Austin, Texas 78712, USA
    Biochemistry 44:13744-52. 2005
    ..Likewise, 2-chloroacetamidine may potentially find wide applicability as a general pharmacophore useful in delineating characteristics of the amidinotransferase superfamily...
  30. ncbi The effect of nNOS inhibitors on toxin-induced cell death in dopaminergic cell lines depends on the extent of enzyme expression
    Monika J Brzozowski
    Neurodegenerative Diseases Research Centre, School of Biomedical Sciences, King s College, London, UK
    Brain Res 1404:21-30. 2011
    ..nNOS is protective against toxic insult when produced endogenously. When nNOS is overexpressed, it becomes neurotoxic to cells suggesting that inhibition of nNOS may be a promising strategy to prevent cell death in PD...
  31. pmc Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury
    Wen Hong Kan
    Center for Surgical Research, University of Alabama at Birmingham, 1670 University Blvd, Birmingham, AL 35294 0019, USA
    J Appl Physiol (1985) 105:1076-82. 2008
    ..These results indicate that increased expression of iNOS following trauma-hemorrhage plays an important role in the induction of hepatic damage under such conditions...
  32. pmc Arylimidamide DB766, a potential chemotherapeutic candidate for Chagas' disease treatment
    Denise da Gama Jaen Batista
    Laboratorio de Biologia Celular, Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
    Antimicrob Agents Chemother 54:2940-52. 2010
    ..Our data clearly show the trypanocidal efficacy of DB766, suggesting that this AIA may represent a new lead compound candidate to Chagas' disease treatment...
  33. ncbi Trypanosoma cruzi: activity of heterocyclic cationic molecules in vitro
    Michele Gabriele de Oliveira Pacheco
    Lab Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, M N C Soeiro, Rio de Janeiro, Brazil
    Exp Parasitol 123:73-80. 2009
    ..cruzi infection...
  34. pmc Induced fit conformational changes of a "reversed amidine" heterocycle: optimized interactions in a DNA minor groove complex
    Manoj Munde
    Department of Chemistry, Georgia State University, P O Box 4098, Atlanta, Georgia 30302 4098, USA
    J Am Chem Soc 129:5688-98. 2007
    ..reverse system has a larger dihedral angle as well as a modified spatial relationship with the groove relative to amidines. Because of the large dihedral, the reversed amidines should have reduced binding to DNA relative to similar ..
  35. ncbi The activity of diguanidino and 'reversed' diamidino 2,5-diarylfurans versus Trypanosoma cruzi and Leishmania donovani
    Chad E Stephens
    Department of Chemistry, Georgia State University, Atlanta, GA 30303 3083, USA
    Bioorg Med Chem Lett 13:2065-9. 2003
    ..The most active compounds were in the reversed amidine series and six exhibited IC(50) values of less than 1 micro mol versus T. cruzi and five gave similar values versus L. donovani...
  36. pmc Large, sequence-dependent effects on DNA conformation by minor groove binding compounds
    Denise S Tevis
    Department of Chemistry, Georgia State University, Atlanta, GA 30302, USA
    Nucleic Acids Res 37:5550-8. 2009
    ..interpreted in terms of a groove structure for A5 which is largely pre-organized for a fit to the heterocyclic amidines. With ATATA the groove is intrinsically wider and must close to bind the compounds tightly...
  37. pmc Amidine dications: isolation and [Fe]-hydrogenase-related hydrogenation
    Michael J Corr
    WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom
    J Am Chem Soc 131:9174-5. 2009
    ....
  38. ncbi Induction of autophagic cell death by a novel molecule is increased by hypoxia
    Marco Tafani
    Department of Cellular and Molecular Pathology, IRCCS San Raffaele Pisana, Rome, Italy
    Autophagy 4:1042-53. 2008
    ..These results indicate that activation of the autophagic pathway in hypoxic cells by the new molecule CR 3294, as well as by TFP or SW, can have potentially important implications for cancer treatment...
  39. ncbi Out-of-shape DNA minor groove binders: induced fit interactions of heterocyclic dications with the DNA minor groove
    Yi Miao
    Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, USA
    Biochemistry 44:14701-8. 2005
    DB921 and DB911 are benzimidazole-biphenyl isomers with terminal charged amidines. DB911 has a central meta-substituted phenyl that gives it a shape similar to those of known minor groove binding compounds...
  40. ncbi Diguanidino and "reversed" diamidino 2,5-diarylfurans as antimicrobial agents
    C E Stephens
    Department of Chemistry, Georgia State University, 1 University Plaza, Atlanta, Georgia 30303-3083, USA
    J Med Chem 44:1741-8. 2001
    ..Finally, when evaluated against an expanded fungal panel, compound 6h showed good activity against Cryptococcus neoformans and Rhizopus arrhizus...
  41. ncbi The origin and development of the vagal and spinal innervation of the external muscle of the mouse esophagus
    Q Sang
    Department of Anatomy and Cell Biology, University of Melbourne, Victoria, Australia
    Brain Res 809:253-68. 1998
    ....
  42. ncbi Mechanism of inactivation of inducible nitric oxide synthase by amidines. Irreversible enzyme inactivation without inactivator modification
    Yaoqiu Zhu
    Department of Chemistry, Drug Discovery Program, Northwestern University, Evanston, Illinois 60208 3113, USA
    J Am Chem Soc 127:858-68. 2005
    ..This appears to be the first example of a compound that causes irreversible inactivation of an enzyme without itself becoming modified in any way...
  43. pmc Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo
    Denise da Gama Jaen Batista
    Laboratorio de Biologia Celular, Fundação Oswaldo Cruz Instituto Oswaldo Cruz, Rio de Janeiro, Brazil
    PLoS ONE 6:e22155. 2011
    ..Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ≥13% of surviving animals...
  44. ncbi In vitro trypanocidal activity of DB745B and other novel arylimidamides against Trypanosoma cruzi
    Cristiane França Da Silva
    Laboratório de Biologia Celular do Instituto Oswaldo Cruz, Fundacao Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
    J Antimicrob Chemother 66:1295-7. 2011
    ..As part of a search for new therapeutic opportunities to treat chagasic patients, in vitro efficacy studies were performed to characterize the activity of five novel arylimidamides (AIAs) against Trypanosoma cruzi...
  45. ncbi In vitro effects of arylimidamides against Besnoitia besnoiti infection in Vero cells
    H C E Cortes
    Laboratório de Parasitologia Victor Caeiro, Núcleo da Mitra, ICAAM, Universidade de Evora, Apartado 94, 7000 554 Evora, Portugal
    Parasitology 138:583-92. 2011
    ..These results show that arylimidamides such as DB811 could potentially become an important addition to the anti-parasitic arsenal for food animal production, especially in cattle...
  46. pmc Cellular effects of reversed amidines on Trypanosoma cruzi
    C F Silva
    Laboratory de Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, Av Brasil 4365, 21040 900 Rio de Janeiro, RJ, Brazil
    Antimicrob Agents Chemother 51:3803-9. 2007
    ..both in vitro and in vivo, our present aim was to evaluate the cellular effects in vitro of three reversed amidines (DB889, DB702, and DB786) and one diguanidine (DB711) against both amastigotes and bloodstream trypomastigotes of ..
  47. ncbi Excess nitric oxide decreases cytochrome P-450 2J4 content and P-450-dependent arachidonic acid metabolism in lungs of rats with acute pneumonia
    Asma Yaghi
    London Health Sciences Research Institute, AC Burton Vascular Biology Laboratory, London Health Sciences Centre, Victoria Campus, 375 South St, London, Ontario, Canada N6A 4G5
    Am J Physiol Lung Cell Mol Physiol 286:L1260-7. 2004
    ..We speculate CYP2J4 and its AA metabolites are involved in the modulation of pulmonary function in health and disease...
  48. ncbi Platelet-activating factor mediates Porphyromonas gingivalis lipopolysaccharide interference with salivary mucin synthesis via phosphatidylinositol 3-kinase-dependent constitutive nitric-oxide synthase activation
    B L Slomiany
    Research Center University of Medicine and Dentistry of New Jersey, Newark, NJ 07103 2400, USA
    J Physiol Pharmacol 55:85-98. 2004
    ..gingivalis infection on salivary glands capacity for mucin production, and suggest that its release in response to the LPS serves as a negative regulator of PI3K controlling the pathway of cNOS activation...
  49. ncbi NOS II inhibition restores attenuation of endothelium-dependent hyperpolarization in rat mesenteric artery exposed to lipopolysaccharide
    Shinji Mitsumizo
    Department of Anesthesiology and Critical Care Medicine, Surgical Center, Saga Medical School, Saga, Japan
    J Cardiovasc Pharmacol 43:589-94. 2004
    ..The possible mechanisms underlying decreased EDHF-mediated responses might be due to, at least in some part, massive nitric oxide induced by NOS II...
  50. ncbi Platelet-activating factor mediates Helicobacter pylori lipopolysaccharide interference with gastric mucin synthesis
    Bronislaw L Slomiany
    Research Center, University of Medicine and Dentistry of New Jersey Dental School, Newark 07103 2400, USA
    IUBMB Life 56:41-6. 2004
    ..Our findings suggest that PAF, through the interference with PI3K-dependent cNOS activation, plays a critical role in influencing the extent of pathological consequences of H. pylori infection on the synthesis of gastric mucin...
  51. ncbi Effects of an inducible nitric oxide synthase inhibitor on experimentally induced rat pulpitis
    Hiromi Nakano Kawanishi
    Pulp Biology and Endodontics, Department of Restorative Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Eur J Oral Sci 112:332-7. 2004
    ..These results suggest that NO may be responsible for the infiltration of immunocompetent cells in the progress of pulpitis, and that 1400W is a promising candidate for controlling pulpal inflammatory reactions...
  52. ncbi Role of inducible nitric oxide synthase expressed by alveolar macrophages in high mobility group box 1--induced acute lung injury
    D Ren
    Department of Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing, 100005, People s Republic of China
    Inflamm Res 55:207-15. 2006
    ..The role of inducible nitric oxide synthase (iNOS) expressed by alveolar macrophages in acute lung injury induced by high mobility group box 1 (HMGB1) was explored...
  53. ncbi High glucose increases B1-kinin receptor expression and signaling in endothelial cells
    Andres I Rodriguez
    Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile
    Biochem Biophys Res Commun 345:652-9. 2006
    ..iNOS protein levels were also increased in high glucose. These results demonstrate the participation of the B1 receptor in the signaling pathways mediated by kinins in high glucose...
  54. ncbi Addition of nitric oxide donor S-nitroso-N-acetylcysteine to selective iNOS inhibitor 1400W further improves contractile function in reperfused skeletal muscle
    Joseph U Barker
    Orthopaedic Research Laboratories, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
    Microsurgery 25:338-45. 2005
    ....
  55. ncbi Increased vasoconstriction to noradrenaline by 1400W, inhibitor of iNOS, in rats with streptozotocin-induced diabetes
    Xing Cheng
    Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3
    Eur J Pharmacol 484:263-8. 2004
    ..0+/-0.2 to 3.8+/-0.3 mmHg) in the diabetic rats. Thus, selective inhibition of iNOS by 1400W increases arterial and venous constriction to noradrenaline in conscious rats with streptozotocin-induced diabetes...
  56. ncbi Inhibition of iNOS with 1400W improves contractile function and alters nos gene and protein expression in reperfused skeletal muscle
    Prerana Patel
    Orthopaedic Microsurgery Laboratory, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
    Microsurgery 24:324-31. 2004
    ..Protection by 1400W at 24-h reperfusion suggests that the role of iNOS in exaggerating reperfusion injury is more prominent in the later stages of injury...
  57. ncbi Effect of nitric oxide synthase (NOS) inhibition on macro- and microcirculation in a model of rat endotoxic shock
    Soni Savai Pullamsetti
    Departmennt of Internal Medicine, Justus Liebig University Giessen, Klinikstrasse 36, 35392 Giessen, Germany
    Thromb Haemost 95:720-7. 2006
    ....
  58. ncbi Inhibition of inducible nitric oxide synthase and superoxide production reduces matrix metalloproteinase-9 activity and restores coronary vasomotor function in rat cardiac allografts
    Koso Egi
    Department of Cardiac Surgery, Ludwig Maximilians University, Munich, Germany
    Eur J Cardiothorac Surg 26:262-9. 2004
    ..We investigated the contribution of inducible nitric oxide synthase (iNOS) derived NO and superoxide on (MMP)-9 activity and to changes in coronary vasomotor function in rat cardiac allografts...
  59. ncbi Coexposure of lead- and lipopolysaccharide-induced liver injury in rats: involvement of nitric oxide-initiated oxidative stress and TNF-alpha
    Ming Yie Liu
    Department of Environmental and Occupational Health, National Cheng Kung University Medical College, Tainan 704, Taiwan
    Shock 23:360-4. 2005
    ..Thus, Pb increased LPS-induced liver damage, which might be associated with increased NO-initiated oxidative stress and TNF-alpha in rats...
  60. pmc Nitric oxide inhibition and the impact on renal nerve-mediated antinatriuresis and antidiuresis in the anaesthetized rat
    N M Bagnall
    Department of Physiology, Aras Windle, University College Cork, Cork, Republic of Ireland
    J Physiol 569:849-56. 2005
    ..The findings suggest that NO importantly modulates the neural control of fluid reabsorption; the control may be facilitatory at a presynaptic level but inhibitory on tubular reabsorptive processes...
  61. ncbi Suppression of experimental aortic aneurysms: comparison of inducible nitric oxide synthase and cyclooxygenase inhibitors
    Peter J Armstrong
    Section of Vascular Surgery, Sigfried and Janet Weis Center for Research, Geisinger Medical Center, Danville, PA 17822 2150, USA
    Ann Vasc Surg 19:248-57. 2005
    ..Inhibition of iNOS limits aneurysmal expansion by mechanisms other than MMP-9 inhibition. MMP-9 inhibition by indomethacin is not sufficient to limit aneurysm expansion in our model...
  62. ncbi Selective inhibition of inducible nitric oxide synthase reduces neurological deficit but not cerebral edema following traumatic brain injury
    G Louin
    Universite Paris Descartes, Faculte de Pharmacie, Laboratoire de Pharmacologie de la Circulation Cérébrale UPRES EA 2510, 4, avenue de l Observatoire, 75270 Paris Cedex 06, France
    Neuropharmacology 50:182-90. 2006
    ..The 6 h therapeutic window of iNOS inhibitors could allow their use in the treatment of functional deficit at the acute phase of TBI...
  63. ncbi Inhibition of iNOS activity by 1400W decreases glutamate release and ameliorates stroke outcome after experimental ischemia
    Fernando J Pérez-Asensio
    Centro de Investigacion, Hospital Universitario La Fe, Valencia, Spain
    Neurobiol Dis 18:375-84. 2005
    ..We have studied the effect of the highly selective inhibitor of iNOS activity 1400W on brain ATP levels, extracellular glutamate, and stroke outcome after transient focal cerebral ischemia in rats...
  64. ncbi Role of nitric oxide during coronary endothelial dysfunction after myocardial infarction
    An Berges
    Laboratory of Cardiology, University of Antwerp, Wilrijkstraat 10, Edegem 2650, Belgium
    Eur J Pharmacol 516:60-70. 2005
    ..Although the NO-mediated response is increased after ischaemia, its final action is restricted due to the presence of superoxide...
  65. ncbi Effects of nitric oxide synthase inhibitor on acid aspiration-induced lung injury in rats
    Ming Yuan Jian
    First Department of Internal Medicine, Shinshu University School of Medicine, 3 1 1 Asahi, Matsumoto 390 8621, Japan
    Pulm Pharmacol Ther 18:33-9. 2005
    ..NOS plays an important role in the pathogenesis of acid aspiration-induced lung injury. Furthermore, selective iNOS inhibition at the optimal dose was most effective in improving lung injury induced by acid aspiration in rats...
  66. ncbi Nitric oxide from inflammatory-activated glia synergizes with hypoxia to induce neuronal death
    Palwinder Mander
    Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, United Kingdom
    J Neurosci Res 79:208-15. 2005
    ..Brain inflammation can thus sensitize to hypoxia-induced death, which may be important in pathologies such as stroke, neurodegeneration, and brain aging...
  67. ncbi Nitric oxide mediates an LPS-induced depression of cytochrome P450 (CYP1A) activity in astrocytes
    Tara E Nicholson
    Department of Pharmacology, Sir Charles Tupper Medical Bldg Dalhousie University Halifax, Nova Scotia, Canada, B3H 4H7
    Brain Res 1029:148-54. 2004
    ..Taken together, these observations suggest that NO plays a pivotal role in the inflammation mediated loss in CYP1A activity in the brain...
  68. ncbi The blockade of cyclopiazonic acid-induced store-operated Ca2+ entry pathway by YC-1 in neutrophils
    Jih Pyang Wang
    Department of Education and Research, Taichung Veterans General Hospital, Taichung 407, Taiwan, Republic of China
    Biochem Pharmacol 68:2053-64. 2004
    ....
  69. ncbi Interleukin (IL)-1beta toxicity to islet beta cells: Efaroxan exerts a complete protection
    Gianpaolo Papaccio
    Department of Experimental Medicine, Section of Histology and Embryology, School of Medicine, 2nd University of Naples, Naples, Italy
    J Cell Physiol 203:94-102. 2005
    ....
  70. ncbi Minocycline or iNOS inhibition block 3-nitrotyrosine increases and blood-brain barrier leakiness in amyloid beta-peptide-injected rat hippocampus
    Jae K Ryu
    Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3
    Exp Neurol 198:552-7. 2006
    ..Our results suggest the involvement of glial-derived reactive nitrogen species in mediating increased BBB permeability in Abeta(1-42) injected rat hippocampus...
  71. ncbi NO-synthase inhibition in sepsis
    Alexander O Spiel
    Thromb Haemost 95:591-2. 2006
  72. ncbi Nitric oxide produced by inducible nitric oxide synthase is associated with mammary tumorigenesis in irradiated rats
    Hiroshi Inano
    Redox Regulation Research Group, Research Center for Radiation Safety, National Institute of Radiological Sciences, 9 1 Anagawa 4 chome, Inage Ku, Chiba 263 8555, Japan
    Nitric Oxide 12:15-20. 2005
    ..These results indicate that iNOS-derived NO may participate in the formation of estrogen-dependent mammary adenocarcinomas following radiation...
  73. pmc Bolus injection of human UII in conscious rats evokes a biphasic haemodynamic response
    Sheila M Gardiner
    Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham, Nottingham
    Br J Pharmacol 143:422-30. 2004
    ....
  74. ncbi Inhibition of nitric oxide synthase reduces renal ischemia/reperfusion injury
    Lisa A Mark
    Department of Surgery, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
    J Surg Res 129:236-41. 2005
    ..In this study the roles of both iNOS and NO were characterized in a rat model of renal I/R injury. In addition, the effect of iNOS inhibition on renal function was evaluated...
  75. ncbi Cytokines and nitric oxide inhibit the enzyme activity of catalase but not its protein or mRNA expression in insulin-producing cells
    L A Sigfrid
    Pharmacy and Biomolecular Sciences, Cockcroft Building, Room 708, University of Brighton, Lewes Road, Brighton BN2 4GJ, UK
    J Mol Endocrinol 31:509-18. 2003
    ..We have shown that inhibition of catalase activity by cytokines is nitric oxide dependent and propose that this inhibition may confer increased susceptibility to cytokine- or nitric oxide-induced cell killing...
  76. ncbi Stress-induced increase in extracellular sucrose space in rats is mediated by nitric oxide
    Jose L M Madrigal
    Departmento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid 28040, Spain
    Brain Res 938:87-91. 2002
    ..Taken together, these findings indicate that iNOS expression mediates stress-induced increase in BBB permeability and support a possible neuroprotective role for specific iNOS inhibitors in this situation...
  77. ncbi Photo-control of nitric oxide synthase activity using a caged isoform specific inhibitor
    Heather J Montgomery
    Department of Chemistry, University of Waterloo, Waterloo, N2L 3G1, Ontario, Canada
    Bioorg Med Chem 10:1919-27. 2002
    ..007+/-0.001 min(-1). A therapeutic range exists, with molar excess of inhibitor to enzyme from 3- to 7-fold, over which the full dynamic range of the inhibition can be exploited...
  78. ncbi Role of myocardial inducible nitric oxide synthase in contractile dysfunction and beta-adrenergic hyporesponsiveness in rats with experimental volume-overload heart failure
    Olga Gealekman
    Bruce Rappaport Faculty of Medicine, The Rappaport Institute, The Bernard Katz Center for Cell Biophysics, Technion, Haifa, Israel
    Circulation 105:236-43. 2002
    ....
  79. ncbi Nitric oxide inhibitors ameliorate indomethacin-induced enteropathy in rats
    G Parasher
    Department of Medicine, SUNY Upstate Medical University, Syracuse, New York 13210, USA
    Dig Dis Sci 46:2536-41. 2001
    ..Our data suggest that NO derived from iNOS may be a key factor in the pathogenesis of acute INDO-induced enteropathy in rats...
  80. ncbi Bioenergetics in cardiac hypertrophy: mitochondrial respiration as a pathological target of NO*
    L Dai
    Departmentof Pathology and Center for Free Radical Biology, University of Alabama at Birmingham, 35294, USA
    Am J Physiol Heart Circ Physiol 281:H2261-9. 2001
    ..We conclude that endogenously generated NO* can modulate mitochondrial function in the hypertrophied heart and suggest that this bioenergetic defect may underlie certain pathological features of hypertrophy...
  81. ncbi Attenuation of Helicobacter pylori endotoxin-provoked rat intestinal inflammation by selective inhibition of the inducible nitric oxide synthase
    Z Szepes
    First Department of Medicine, University of Szeged, Hungary
    J Physiol Paris 95:453-5. 2001
    ..Systemic liberation of H. pylori endotoxin might possibly attenuate jejunal and colonic mucosal barrier function, a process mediated by the expression of the inducible nitric oxide synthase...
  82. pmc Apocynin and 1400 W prevents airway hyperresponsiveness during allergic reactions in mice
    R B Muijsers
    Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands
    Br J Pharmacol 134:434-40. 2001
    ..This mechanism, however, is not reflected by 3-nitrotyrosine formation in the airways...
  83. ncbi N-(3-(aminomethyl)benzyl)acetamidine, an inducible nitric oxide synthase inhibitor, decreases colonic inflammation induced by trinitrobenzene sulphonic acid in rats
    L A Menchén
    Departamento de Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    Life Sci 69:479-91. 2001
    ..These findings indicate that the expression of iNOS accounts for most of the damage caused by TNBS and that the administration of 1400W after the onset of colitis has a beneficial action on the colonic injury...
  84. ncbi Differential effects of selective and non-selective inhibition of nitric oxide synthase on the expression and activity of cyclooxygenase-2 during gastric ulcer healing
    Jin Sheng Guo
    Division of Gastroenterology, Department of Internal Medicine, Zhong Shan Hospital, Shanghai Medical College, Fu Dan University, Shanghai, China
    Eur J Pharmacol 536:301-8. 2006
    ..It is concluded that iNOS may contribute to ulcer formation while COX-2 and eNOS promote ulcer healing. eNOS enhances COX-2 expression possibly through the activation of NF-kappaB...
  85. ncbi Helicobacter pylori lipopolysaccharide-provoked injury to rat gastroduodenal microvasculature involves inducible nitric oxide synthase
    J Kiss
    First Department of Medicine, University Medical School of Szeged, Hungary
    Eur J Pharmacol 420:175-9. 2001
    ..Thus, H. pylori lipopolysaccharide can initiate the expression of iNOS in the stomach and duodenum following systemic challenge, which can provoke gastroduodenal microvascular dysfunction...
  86. ncbi Mechanical stress and nitric oxide influence leukotriene production in cartilage
    B Fermor
    Department of Surgery, Division of Orthopedic Surgery, Duke University Medical Center, Durham, NC 27710, USA
    Biochem Biophys Res Commun 285:806-10. 2001
    ..These findings provide a direct link between mechanical stress and inflammation in cartilage and may have implications in the pathogenesis and treatment of arthritis...
  87. ncbi Nitric oxide induces MIP-2 transcription in rat renal mesangial cells and in a rat model of glomerulonephritis
    S Walpen
    Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe Universitat, Frankfurt am Main, Germany, daggerAbteilung für Innere Medizin, Universitat Munster, Munster, Germany
    FASEB J 15:571-3. 2001
    ..Furthermore, infiltration of neutrophils into the glomerulus was dramatically attenuated in L-NIL-treated rats...
  88. ncbi Nitric oxide synthase inhibitors have opposite effects on acute inflammation depending on their route of administration
    M J Paul-Clark
    Department of Experimental Pathology, The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, United Kingdom
    J Immunol 166:1169-77. 2001
    ....
  89. pmc Dual effect of nitric oxide in articular inflammatory pain in zymosan-induced arthritis in rats
    José C da S Rocha
    Faculdade de Medicina Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceara, Rua Cel Nunes de Melo, 1127 CEP 60430 270, Fortaleza Ceará Brasil
    Br J Pharmacol 136:588-96. 2002
    ..This was not due to inhibition of articular PGE(2) release or oedema. NO donors also promoted antinociception in zymosan arthritis without affecting oedema...
  90. ncbi Inhibition of spinal constitutive NOS-2 by 1400W attenuates tissue injury and inflammation-induced hyperalgesia and spinal p38 activation
    Qingbo Tang
    Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA
    Eur J Neurosci 25:2964-72. 2007
    ....
  91. ncbi Comparison of iNOS inhibition by antisense and pharmacological inhibitors after spinal cord injury
    D D Pearse
    The Miami Project to Cure Paralysis and the Department of Neurological Surgery, University of Miami School of Medicine, Miami, Florida 33136, USA
    J Neuropathol Exp Neurol 62:1096-107. 2003
    ..Furthermore, we demonstrate that the antisense inhibition of iNOS is more efficacious than currently available pharmacological agents...
  92. ncbi Effect of a potent iNOS inhibitor (ONO-1714) on acetaminophen-induced hepatotoxicity in the rat
    Yoshihisa Kamanaka
    Minase Research Institute, Ono Pharmaceutical Co Ltd, Osaka 618 8585, Japan
    Life Sci 74:793-802. 2003
    ....
  93. ncbi Relationship between cyclooxygenase-2 and nitric oxide synthase-2 in rat cortex after stress
    Jose L M Madrigal
    Department of Pharmacology, Faculty of Medicine, University Complutense, 28040 Madrid, Spain
    Eur J Neurosci 18:1701-5. 2003
    ..These findings are discussed as possible therapeutic targets in the context of neuropsychiatric disorders related to stress...
  94. ncbi Roles of iNOS and nNOS in sepsis-induced pulmonary apoptosis
    Jill C Rudkowski
    Rm L3 03, Critical Care Division, Royal Victoria Hospital, 687 Pine Ave West, Montreal, H3A 1A1 Quebec, Canada
    Am J Physiol Lung Cell Mol Physiol 286:L793-800. 2004
    ..By comparison, genetic deletion of the neuronal NOS had no effect on LPS-induced pulmonary apoptosis. We conclude that NO derived from iNOS plays an important protective role against sepsis-induced pulmonary apoptosis...
  95. ncbi Type II nitric oxide synthase activity is cardio-protective in experimental sepsis
    Suzanna Price
    Unit of Critical Care Medicine, Imperial College School of Medicine, Royal Brompton Hospital, Dovehouse Street, London SW3 6LY, UK
    Eur J Pharmacol 472:111-8. 2003
    ..These findings suggest that NOSII is cardio-protective in the heart in sepsis and explain why its inhibition in man led to increased mortality in a subpopulation of patients...
  96. ncbi Highly selective inhibitor of inducible nitric oxide synthase enhances S-antigen-induced uveitis
    Frederic Charlotte
    Department of Pathology, Pitie Salpetriere Hospital, Paris, France
    Curr Eye Res 26:1-7. 2003
    ..Investigated the effect of N-3-aminomethylbenzylacetamidine (1400 W), a highly selective inhibitor of inducible nitric oxide synthase (iNOS), on the effector phase of EAU...
  97. ncbi Selective versus non-selective suppression of nitric oxide synthase on regional hemodynamics in rats with or without LPS-induced endotoxemia
    Xing Cheng
    Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, 2176 Health Sciences Mall, Vancouver, B C V6T 1Z3, Canada
    Naunyn Schmiedebergs Arch Pharmacol 367:372-9. 2003
    ..Therefore, selective inhibition of iNOS by 1400 W restores MAP without compromising CO, but non-selective inhibition of NOS is detrimental at the late stage of septic shock...
  98. ncbi Angiotensin II type 1 receptor blocker preserves tolerance to ischemia-reperfusion injury in Dahl salt-sensitive rat heart
    Seiji Matsuhisa
    Second Department of Internal Medicine, Kansai Medical University, Moriguchi City, Japan
    Am J Physiol Heart Circ Physiol 294:H2473-9. 2008
    ..These results suggest that losartan preserves the tolerance to I/R injury by activating eNOS despite elimination of redox-sensitive upregulation of iNOS and iNOS-dependent cardioprotection in the DS rat heart...
  99. ncbi Pharmacological assessment of the nitric-oxide synthase isoform involved in eosinophilic inflammation in a rat model of sephadex-induced airway inflammation
    Mark A Birrell
    Respiratory Pharmacology, Cardiothoracic Surgery, Imperial College of Science, Technology and Medicine, Faculty of Medicine, National Heart and Lung Institute, London, United Kingdom
    J Pharmacol Exp Ther 304:1285-91. 2003
    ....
  100. ncbi High tidal volume ventilation induces NOS2 and impairs cAMP- dependent air space fluid clearance
    James A Frank
    Cardiovascular Research Institute, University of California, San Francisco 94143 0130, USA
    Am J Physiol Lung Cell Mol Physiol 284:L791-8. 2003
    ..Because air space edema fluid inactivates surfactant and reduces ventilated lung volume, the reduction of cAMP-dependent AFC by reactive nitrogen species may be an important mechanism of clinical ventilator-associated lung injury...
  101. ncbi Reperfusion injury is reduced in skeletal muscle by inhibition of inducible nitric oxide synthase
    Li Zhang
    Orthopaedic Microsurgery Laboratory, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Appl Physiol 94:1473-8. 2003
    ..Thus 1400W may have therapeutic potential in treatment of ischemia-reperfusion injury...

Research Grants51

  1. Improving in vivo stability of sphingosine kinase inhibitors
    STEVEN BRANDON THORPE; Fiscal Year: 2012
    ..Herein we outline a set of strategies including pro-drug forms, modified amidines, guanidines, etc. to render the SphK1 inhibitors drug like...
  2. CARCINOGENESIS--NITROSAMINE FORMATION AND INHIBITION
    RICHARD LOEPPKY; Fiscal Year: 1999
    ..across the C=N is responsible for the rapid formation of nitrosamines and highly reactive diazonium ions from amidines, imidates, thioimidates, geminal diamines and their S and O analogs, and certain benzylic-like amines linked to ..
  3. Azides as Synthons for Isonitriles: Facilitating Challenging Coupling Reactions
    JENNIFER LYNN STOCKDILL; Fiscal Year: 2010
    ..Modification of the method to employ amidines will enable the rapid and modular synthesis of novel cyclosporine analogs...
  4. DRUG DEVELOPMENT FOR SECONDARY INFECTIONS OF AIDS
    Rolf Winter; Fiscal Year: 1999
    ..Many parasites require heme due to biochemical insufficiencies. We predict that placement of alkylamines or amidines at the 4 and 5 positions of the xanthone nucleus will lead to enhanced heme binding and consequently increased ..
  5. SUPPRESSION OF EROSIVE ARTHRITIS BY PROTEASE INHIBITORS
    JOACHIM GERATZ; Fiscal Year: 1992
    ..Interest in amidines arose when preliminary experimental studies showed that BABIM (bis-(5-amidino-2-benzimidazolyl)methane) can block ..
  6. Novel Leads for the Therapy of Gram-Positive Sepsis
    Sunil David; Fiscal Year: 2004
    ..activity, useful leads have been found in three classes: (1) the lipopolyamines (2) dendrimers, and (3) bis-amidines. Focused libraries of these compounds will be subjected to two levels of screening...
  7. FUNCTIONAL PATHWAYS OF THE COCHLEAR NUCLEUS
    JOHN DOUCET; Fiscal Year: 2002
    ..abstract_text> ..
  8. Studies of the Central Auditory System
    Bradford May; Fiscal Year: 2007
    ..abstract_text> ..
  9. Gene transfer to the kidney using lentiviral vectors
    Frank Park; Fiscal Year: 2004
    ..abstract_text> ..
  10. Afferent modulation in bladde dysfunction
    Naoki Yoshimura; Fiscal Year: 2007
    ..abstract not provided ..
  11. Chemoprevention Potential of Calpain Inhibitors
    ISAAC DONKOR; Fiscal Year: 2007
    ..The proposal is significant and innovative because it seeks to investigate calpain as a pharmacological target for the discovery of a new class of chemoprevention agents. [unreadable] [unreadable] [unreadable]..
  12. Water-Soluble and Metabolically Stable Calpain Inhibitors as Cardioprotectants
    ISAAC DONKOR; Fiscal Year: 2008
    ..Furthermore, the proposed studies will provide mechanistic insight into the mode of action of calpain inhibitors as cardioprotectants. ..
  13. Effects of Antioxidants on Human Macular Pigments
    Kyung Jin Yeum; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  14. Neurophysiology and Biomechanics of Urethra in Stress Urinary Incontinence
    Naoki Yoshimura; Fiscal Year: 2008
    ..This is recognized as a high priority in the urologic/gynecologic care of SUI patients. [unreadable] [unreadable]..
  15. Cardiovascular Response to Glutamate Nitric Oxide
    WILLIAM TALMAN; Fiscal Year: 2006
    ..e. on nNOS immunoreactive dendrites or neurons in NTS. ..
  16. Structure/Function of the Bacterial TRCF
    Seth Darst; Fiscal Year: 2008
    ..3. Determine the structural basis for the specific transcription termination activity of TRCF through structural studies of an RNAP ternary elongation complex (RNAP/DNA/RNA) with TRCF. ..
  17. New Methods for the Synthesis of Neurological Agents
    LARRY OVERMAN; Fiscal Year: 2008
    ..oryzae at 90 nM, suggesting potential antitumor activity. Because of the scarcity of these natural products from their natural sources, little biological evaluation has been carried out. ..
  18. ANATOMY OF THE PRIMATE AMYGDALOID COMPLEX
    David G Amaral; Fiscal Year: 2010
    ..This work provides essential normative data to study influences like circulating hormones or social experience on amygdala maturation. ..
  19. Structural Basis for Sporulation in Bacillus
    Seth A Darst; Fiscal Year: 2010
    ..4. Structurally characterize the ?F regulatory system (?F/SpollAA/SpollAB/SpollE) controlling the initiation of Bacillus sporulation. ..
  20. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2010
    ....
  21. Noninvasive Quantification of Axon Damage in EAE and MS
    Sheng Kwei Song; Fiscal Year: 2010
    ..In both strains, the extent of axonal damage will closely relate to the duration of the acute peaking of neurological deficits - presumably caused by acute inflammatory responses. ..
  22. AFFERENT PLASTICITY UNDERLYING URETHRAL AND PELVIC PAIN
    Naoki Yoshimura; Fiscal Year: 2010
    ..This is recognized as a high priority in the urologic care of patients with IC/CPPS. ..
  23. X-RAY CRYSTALLOGRAPHIC STUDIES OF TAQ RNA POLYMERASE
    Seth Darst; Fiscal Year: 2008
    ..Determine the crystal structure of RNAP with the transcription elongation factor GreA/B; 5. Determine the crystal structure of T. thermophilus sigma (E) holoenzyme. ..
  24. PRACTICAL CHEMICAL SYNTHESIS OF COMPLEX ALKALOIDS
    LARRY OVERMAN; Fiscal Year: 2009
    ....
  25. Molecular Foundations of the Myoclonus-Dystonia Syndrome
    Mark leDoux; Fiscal Year: 2006
    ..We hypothesize that epsilon sarcoglycan co-localizes with GABA receptors opposite GABAergic terminals in the central nervous system. ..
  26. Upgrade of in-house X-ray diffraction equipment
    Seth Darst; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  27. EYELID SENSORIMOTOR NETWORKS
    Mark leDoux; Fiscal Year: 2003
    ..abstract_text> ..
  28. Lower urinary tract dysfunction in Parkinson's disease
    Naoki Yoshimura; Fiscal Year: 2003
    ..This is a high priority in the urologic care of patients with Parkinson's disease. ..
  29. Upgrade of mass spectrometer facility
    Michael Thomas; Fiscal Year: 2003
    ..The new mass spectrometer will provide 1) a significant increase in detection sensitivity, 2) higher resolution, 3) greater accuracy of mass measurement, 4) increased reliability, and 5) compatibility with new generations of software. ..
  30. TRAINING PROGRAM IN SYSTEMS NEUROSCIENCE
    David Amaral; Fiscal Year: 2002
    ..abstract_text> ..
  31. NEUROTROPHIN 3 IN NEURONAL INJURY AND DISEASE
    Douglas Wright; Fiscal Year: 2002
    ..Results from these studies will define new biological actions of NT-3 and reveal how manipulation of the trophic support of neurons may be useful to treat pathologic neural conditions. ..
  32. NEUROBIOLOGY OF PRIMATE SOCIAL BEHAVIOR
    David Amaral; Fiscal Year: 2002
    ..These studies will provide important insights into the neurobiology of normal social behavior and may contribute to an understanding of pathologies of social communication in disorders such as autism. ..
  33. PROBING THE S' SUBSITES OF CALPAIN
    ISAAC DONKOR; Fiscal Year: 2002
    ..Selected potent and cell permeable inhibitors will be tested in the rat isolated heart ischemia model for cardioprotective effect. ..
  34. STRUCTURAL PARAMETERS OF E COLI RNA POLYMERASE
    Seth Darst; Fiscal Year: 2001
    ....
  35. CARCINOGENESIS--HIGHLY REACTIVE NITROSAMINES
    RICHARD LOEPPKY; Fiscal Year: 2001
    ....
  36. ENDOGENOUS NITROSATION CHEMISTRY IN CARCINOGENESIS
    RICHARD LOEPPKY; Fiscal Year: 2004
    ..Computational methods will be employed to reveal reaction paths of intermediates and lead to better predictions of the types of compounds which pose a carcinogenic threat through their endogenous nitrosation. ..
  37. FUNCTIONAL ANATOMY OF MOUSE CORTICOHIPPOCAMPAL SYSTEMS
    REBECCA BURWELL; Fiscal Year: 2004
    ..Another major aim of the proposed studies is to use neuropsychological approaches within a comparative framework to investigate the function of specific target structures. ..
  38. TETRAHYDROISOQUINOLINES AND PARKINSON'S DISEASE
    Mark leDoux; Fiscal Year: 2006
    ..Evolution may have not provided neurons with mechanisms to prevent accumulation of these by-products of normal metabolism and, as a consequence, susceptible neuronal populations may slowly undergo apoptotic death in the elderly. ..
  39. Bladder Pain Gene Therapy with Pro-opiomelanocortin cDNA
    Naoki Yoshimura; Fiscal Year: 2004
    ..This research project is important to provide a solid basis for potential future clinical application. ..
  40. Targeting Calpain for Novel Anticancer Agents
    ISAAC DONKOR; Fiscal Year: 2005
    ..Additionally, the compounds are useful biomedical tools for investigating the intracellular roles of Calpain due to their metabolic stability. The compounds are also potential anticancer agents. ..
  41. Interdisciplinary Investigation of Biological Signatures of Autism Subtypes
    JUDY A VAN DE WATER; Fiscal Year: 2010
    ..We already have strong evidence for at least an autoimmune type of autism and this research will lead to more effective efforts at preventing future cases of autism and treating existing children with autism. ..
  42. Mutant Gene Identification in the Dystonic Rat
    Mark leDoux; Fiscal Year: 2008
    ..Patients with dystonia will be screened for mutations in the human homologue. These proposed studies will likely increase our understanding of both dystonia and olivocerebellar motor systems. ..
  43. API 4000 QTRAP
    Samuel Poloyac; Fiscal Year: 2007
    ..The acquisition of this hybrid triple quadrupole/linear ion trap mass spectrometer would provide essential instrumentation for this research and thereby remove impediments to research progress. [unreadable] [unreadable] [unreadable]..
  44. The Role of 20-HETE in the Pathogenesis of Stroke
    Samuel Poloyac; Fiscal Year: 2009
    ..Furthermore, these studies will provide important information about the role of monohydroxylated arachidonic acid metabolites as a contributing pathway in the pathogenesis of stroke. ..
  45. Study of a New Class of Chiral Nucleophilic Catalysts
    VLADIMIR BIRMAN; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  46. Bilirubin and Photobilirubin: Metabolism & Exretion
    Antony McDonagh; Fiscal Year: 2005
    ..The work will lead to safer more effective treatment of familial hyperbilirubinemia and jaundice in the newborn. ..
  47. Use Dependent Plasticity of Spinal Inhibition
    NIRANJALA TILLAKARATNE; Fiscal Year: 2006
    ..This work will lead to better ways of testing the effectiveness of alternative training strategies and associated pharmacological interventions. ..
  48. Polyamines and Breast Cancer Biology
    Andrea Manni; Fiscal Year: 2005
    ..The ultimate goal of these studies is to identify critical signaling molecules which can be targeted in conjunction with antipolyamine therapy to optimize prevention of metastasis from breast cancer. ..
  49. POLYAMINE INVOLVEMENT IN MAMMARY CARCINOGENESIS
    Andrea Manni; Fiscal Year: 2001
    ....
  50. Implications of Hypothermia on Hepatic Drug Metabolism
    Samuel Poloyac; Fiscal Year: 2009
    ..Once completed, this research will provide critical information to design future clinical studies to optimize the benefits of this breakthrough therapy. ..
  51. Nanoparticle targeting of cathepsin-L inhibitor and doxorubicin in breast cancer
    Shaker Mousa; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..