Jon Mabley

Summary

Affiliation: Inotek Pharmaceuticals Corporation
Country: USA

Publications

  1. pmc Inhibition of poly (ADP-ribose) synthetase by gene disruption or inhibition with 5-iodo-6-amino-1,2-benzopyrone protects mice from multiple-low-dose-streptozotocin-induced diabetes
    J G Mabley
    Inotek Corporation, Suite 419E, 100 Cummings Center, Beverly, Massachusetts MA 01915, USA
    Br J Pharmacol 133:909-19. 2001
  2. ncbi request reprint Inosine reduces inflammation and improves survival in a murine model of colitis
    J G Mabley
    Inotek Pharmaceuticals, Beverly, Massachusetts 01915, USA
    Am J Physiol Gastrointest Liver Physiol 284:G138-44. 2003
  3. ncbi request reprint The adenosine A3 receptor agonist, N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide, is protective in two murine models of colitis
    Jon Mabley
    Inotek Pharmaceuticals Corporation, Suite 419E, 100 Cummings Center, Beverly, MA 01915, USA
    Eur J Pharmacol 466:323-9. 2003
  4. ncbi request reprint NFkappaB1 (p50)-deficient mice are not susceptible to multiple low-dose streptozotocin-induced diabetes
    J G Mabley
    Inotek Corporation, Suite 419E, 100 Cummings Center, Beverly, MA 01915, USA
    J Endocrinol 173:457-64. 2002
  5. ncbi request reprint Nicotine reduces the incidence of type I diabetes in mice
    J G Mabley
    Inotek Corporation, Beverly, Massachusetts 01915, USA
    J Pharmacol Exp Ther 300:876-81. 2002
  6. pmc Inosine protects against the development of diabetes in multiple-low-dose streptozotocin and nonobese diabetic mouse models of type 1 diabetes
    Jon G Mabley
    Inotek Pharmaceuticals Corp, Beverly, MA 01915, USA
    Mol Med 9:96-104. 2003
  7. ncbi request reprint Suppression of intestinal polyposis in Apcmin/+ mice by targeting the nitric oxide or poly(ADP-ribose) pathways
    Jon G Mabley
    Inotek Pharmaceuticals Corporation, 100 Cummings Center, Suite 419E, Beverly, MA 01915, USA
    Mutat Res 548:107-16. 2004
  8. ncbi request reprint Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose) synthetase: potent cytoprotective and antishock agents
    Prakash Jagtap
    Inotek Corporation, Beverly, MA 01915, USA
    Crit Care Med 30:1071-82. 2002
  9. ncbi request reprint Inhibition of poly (ADP-ribose) polymerase attenuates acute lung injury in an ovine model of sepsis
    Kazunori Murakami
    Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, Texas, 77555, USA
    Shock 21:126-33. 2004
  10. ncbi request reprint The discovery and synthesis of novel adenosine substituted 2,3-dihydro-1H-isoindol-1-ones: potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)
    Prakash G Jagtap
    Inotek Pharmaceuticals Corporation, 100 Cummings Center, Suite 419E, Beverly, MA 01915, USA
    Bioorg Med Chem Lett 14:81-5. 2004

Collaborators

Detail Information

Publications42

  1. pmc Inhibition of poly (ADP-ribose) synthetase by gene disruption or inhibition with 5-iodo-6-amino-1,2-benzopyrone protects mice from multiple-low-dose-streptozotocin-induced diabetes
    J G Mabley
    Inotek Corporation, Suite 419E, 100 Cummings Center, Beverly, Massachusetts MA 01915, USA
    Br J Pharmacol 133:909-19. 2001
    ....
  2. ncbi request reprint Inosine reduces inflammation and improves survival in a murine model of colitis
    J G Mabley
    Inotek Pharmaceuticals, Beverly, Massachusetts 01915, USA
    Am J Physiol Gastrointest Liver Physiol 284:G138-44. 2003
    ..Inosine also partially reduced these parameters in an experimental model of established colitis. Thus inosine treatment may be a potential therapy in colitis...
  3. ncbi request reprint The adenosine A3 receptor agonist, N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide, is protective in two murine models of colitis
    Jon Mabley
    Inotek Pharmaceuticals Corporation, Suite 419E, 100 Cummings Center, Beverly, MA 01915, USA
    Eur J Pharmacol 466:323-9. 2003
    ..Thus activation of the adenosine A(3) receptor is effective in protecting against colitis...
  4. ncbi request reprint NFkappaB1 (p50)-deficient mice are not susceptible to multiple low-dose streptozotocin-induced diabetes
    J G Mabley
    Inotek Corporation, Suite 419E, 100 Cummings Center, Beverly, MA 01915, USA
    J Endocrinol 173:457-64. 2002
    ..Our data suggest that NFkappaB (p50) has an essential role in the development of autoimmune diabetes. Selective therapeutic blockade of this subunit may be beneficial in preventing IDDM...
  5. ncbi request reprint Nicotine reduces the incidence of type I diabetes in mice
    J G Mabley
    Inotek Corporation, Beverly, Massachusetts 01915, USA
    J Pharmacol Exp Ther 300:876-81. 2002
    ..Nicotine treatment reduces the incidence of type I diabetes in two animal models by changing the profile of pancreatic cytokine expression from Th1 to Th2...
  6. pmc Inosine protects against the development of diabetes in multiple-low-dose streptozotocin and nonobese diabetic mouse models of type 1 diabetes
    Jon G Mabley
    Inotek Pharmaceuticals Corp, Beverly, MA 01915, USA
    Mol Med 9:96-104. 2003
    ..The use of inosine should be considered as a potential preventative therapy in humans susceptible to developing Type 1 diabetes and as a possible antirejection therapy for islet transplant recipients...
  7. ncbi request reprint Suppression of intestinal polyposis in Apcmin/+ mice by targeting the nitric oxide or poly(ADP-ribose) pathways
    Jon G Mabley
    Inotek Pharmaceuticals Corporation, 100 Cummings Center, Suite 419E, Beverly, MA 01915, USA
    Mutat Res 548:107-16. 2004
    ....
  8. ncbi request reprint Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose) synthetase: potent cytoprotective and antishock agents
    Prakash Jagtap
    Inotek Corporation, Beverly, MA 01915, USA
    Crit Care Med 30:1071-82. 2002
    ....
  9. ncbi request reprint Inhibition of poly (ADP-ribose) polymerase attenuates acute lung injury in an ovine model of sepsis
    Kazunori Murakami
    Department of Anesthesiology, The University of Texas Medical Branch and Shriners Burns Hospital, Galveston, Texas, 77555, USA
    Shock 21:126-33. 2004
    ..In conclusion, inhibition of PARP improved the ALI after smoke inhalation and pneumonia. The results suggest that the activation of PARP plays a role in the pathophysiology of ALI in sheep...
  10. ncbi request reprint The discovery and synthesis of novel adenosine substituted 2,3-dihydro-1H-isoindol-1-ones: potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1)
    Prakash G Jagtap
    Inotek Pharmaceuticals Corporation, 100 Cummings Center, Suite 419E, Beverly, MA 01915, USA
    Bioorg Med Chem Lett 14:81-5. 2004
    ..Introduction of piperazine and succinyl linkers between the isoindolinone and adenosine core structures resulted in highly potent compounds 8a and 10b, which showed IC(50) values of 45 and 100 nM, respectively...
  11. ncbi request reprint Activation of poly(ADP-ribose) polymerase in circulating leukocytes during myocardial infarction
    Kanneganti G K Murthy
    Inotek Pharmaceuticals Corporation, Beverly, MA 01915, USA
    Shock 21:230-4. 2004
    ..PARP activation in circulating cells may mediate certain systemic effects of local ischemia-reperfusion injury such as inflammatory mediator production and remote organ injury...
  12. ncbi request reprint Effects of poly(ADP-ribose) polymerase inhibition on inflammatory cell migration in a murine model of asthma
    Laszlo Virag
    Department of Medical Chemistry, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
    Med Sci Monit 10:BR77-83. 2004
    ..Since chemokines are principal regulators of mononuclear and polymorphonuclear cell trafficking in asthma, we investigated the possibility whether PARP modulates chemokine production and cell recruitment in a murine model of asthma...
  13. ncbi request reprint The combined inducible nitric oxide synthase inhibitor and free radical scavenger guanidinoethyldisulfide prevents multiple low-dose streptozotocin-induced diabetes in vivo and interleukin-1beta-induced suppression of islet insulin secretion in vitro
    Jon G Mabley
    Inotek Pharmaceuticals Corp, Beverly, Massachusetts, USA
    Pancreas 28:E39-44. 2004
    ..In conclusion, inhibiting formation and/or scavenging reactive nitrogen or oxygen species with GED protects against development of diabetes in vivo and isolated pancreatic islets of Langerhans from cytokine inhibitory effects in vitro...
  14. pmc Adenosine receptor activation ameliorates type 1 diabetes
    Zoltán H Németh
    Department of Surgery, UMDNJ New Jersey Medical School, 185 South Orange Ave, University Heights, Newark, NJ 07103, USA
    FASEB J 21:2379-88. 2007
    ..These results demonstrate that adenosine receptor ligands are potential candidates for the treatment of type 1 diabetes...
  15. pmc A new, potent poly(ADP-ribose) polymerase inhibitor improves cardiac and vascular dysfunction associated with advanced aging
    Pal Pacher
    National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Park Bldg Rm 445, 12420 Parklawn Drive, MSC 8115, Bethesda, MD 20892 8115, USA
    J Pharmacol Exp Ther 311:485-91. 2004
    ..Thus, pharmacological inhibition of PARP may represent a novel approach to improve cardiac and vascular dysfunction associated with aging...
  16. ncbi request reprint Role for nitrosative stress in diabetic neuropathy: evidence from studies with a peroxynitrite decomposition catalyst
    Irina G Obrosova
    Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
    FASEB J 19:401-3. 2005
    ..This provides the rationale for development of agents counteracting peroxynitrite formation and promoting peroxynitrite decomposition, and their evaluation in DN...
  17. ncbi request reprint Potential role for 8-oxoguanine DNA glycosylase in regulating inflammation
    Jon G Mabley
    School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building, Lewes Road, Brighton BN2 4GJ, UK
    FASEB J 19:290-2. 2005
    ..The current studies unveil a role for OGG-1 in the regulation of inflammation...
  18. pmc Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic complications. Emerging new therapeutical strategies
    Pal Pacher
    Laboratory of Physiologic Studies, National Institutes of Health, NIAAA, Bethesda, MD 20892 9413, USA
    Curr Med Chem 12:267-75. 2005
    ....
  19. ncbi request reprint Discovery of potent poly(ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone
    Prakash G Jagtap
    Inotek Pharmaceuticals Corporation, 100 Cummings Center, Suite 419E, Beverly, MA 01915, USA
    J Med Chem 48:5100-3. 2005
    ..The 9-sulfonamide analogues 11a and 12a exhibited IC(50) values of 1 and 10 nM, respectively...
  20. pmc Beneficial effects of a novel ultrapotent poly(ADP-ribose) polymerase inhibitor in murine models of heart failure
    Pal Pacher
    National Institutes of Health, NAAA, Bethesda, MD 20892 9413, USA
    Int J Mol Med 17:369-75. 2006
    ..The current data strengthen the view that PARP inhibition may represent an effective approach for the experimental therapy of various forms of acute and chronic heart failure...
  21. ncbi request reprint Poly (ADP-ribose) polymerase inhibition prevents spontaneous and recurrent autoimmune diabetes in NOD mice by inducing apoptosis of islet-infiltrating leukocytes
    Wilma L Suarez-Pinzon
    Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
    Diabetes 52:1683-8. 2003
    ..These results suggest that PARP inhibition protects against autoimmune beta-cell destruction in NOD mice by inducing apoptosis of islet-infiltrating leukocytes and decreasing IFN-gamma expression in the islets...
  22. pmc Part I: pathogenetic role of peroxynitrite in the development of diabetes and diabetic vascular complications: studies with FP15, a novel potent peroxynitrite decomposition catalyst
    Csaba Szabo
    Inotek Pharmaceuticals Corporation, Beverly, Massachusetts, USA
    Mol Med 8:571-80. 2002
    ..The aim of the current work was to produce a potent peroxynitrite decomposition catalyst and to test its effects in rodent models of diabetes and its complications...
  23. ncbi request reprint Effect of poly(ADP ribose) synthetase inhibition on burn and smoke inhalation injury in sheep
    Katsumi Shimoda
    Department of Anesthesiology, The University of Texas Medical Branch, Shriners Burns Hospital, Galveston, Texas 77555 0833, USA
    Am J Physiol Lung Cell Mol Physiol 285:L240-9. 2003
    ..We conclude that PARS inhibition attenuates various aspects of the pathophysiological response in a clinically relevant experimental model of burn/smoke inhalation injury...
  24. pmc Inosine exerts a broad range of antiinflammatory effects in a murine model of acute lung injury
    Lucas Liaudet
    Inotek Corporation, Beverly, Massachusetts 01915, USA
    Ann Surg 235:568-78. 2002
    ..To investigate the effects of inosine on the acute lung inflammation induced by lipopolysaccharide (LPS) in vivo and on the activation and cytotoxicity elicited by proinflammatory cytokines on human lung epithelial (A549) cells in vitro...
  25. ncbi request reprint Na+/H+ exchanger blockade inhibits enterocyte inflammatory response and protects against colitis
    Zoltán H Németh
    Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA
    Am J Physiol Gastrointest Liver Physiol 283:G122-32. 2002
    ..Finally, NHE inhibition ameliorated the course of IBD in dextran sulfate-treated mice. Our data demonstrate that inhibition of NHEs may be an approach worthy of pursuing for the treatment of IBD...
  26. ncbi request reprint Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice
    Francisco Garcia Soriano
    Inotek Corporation, Beverly, Massachusetts 01915, USA
    Shock 17:286-92. 2002
    ..Thus, PARP activation has an important role in systemic inflammation and organ damage in the present model of polymicrobial septic shock...
  27. pmc Part II: beneficial effects of the peroxynitrite decomposition catalyst FP15 in murine models of arthritis and colitis
    Jon G Mabley
    Inotek Pharmaceuticals Corporation, Cummings Center, Beverly, Massachusetts 01905, USA
    Mol Med 8:581-90. 2002
    ..Here, using a novel peroxynitrite decomposition catalyst, FP15, we directly investigate the role of peroxynitrite in the pathogenesis of arthritis and colitis in rodent models...
  28. pmc Comparison of inflammation, organ damage, and oxidant stress induced by Salmonella enterica serovar Muenchen flagellin and serovar Enteritidis lipopolysaccharide
    Lucas Liaudet
    Department of Surgery, New Jersey Medical School, UMDNJ, Newark, New Jersey 01703, USA
    Infect Immun 70:192-8. 2002
    ..Our data support a novel concept implicating flagellin as a mediator of systemic inflammation, oxidant stress, and organ damage induced by gram-negative bacteria...
  29. ncbi request reprint Flagellin from gram-negative bacteria is a potent mediator of acute pulmonary inflammation in sepsis
    Lucas Liaudet
    Inotek Pharmaceuticals Corporation, Beverly, MA 01915, USA
    Shock 19:131-7. 2003
    ..Flagellin emerges as a potent trigger of acute respiratory complications in gram-negative bacterial sepsis...
  30. ncbi request reprint Potent metalloporphyrin peroxynitrite decomposition catalyst protects against the development of doxorubicin-induced cardiac dysfunction
    Pal Pacher
    Inotek Pharmaceuticals Corp, Beverly, Mass 01915, USA
    Circulation 107:896-904. 2003
    ....
  31. ncbi request reprint Gender differences in the endotoxin-induced inflammatory and vascular responses: potential role of poly(ADP-ribose) polymerase activation
    Jon G Mabley
    Inotek Pharmaceuticals Corporation, Beverly, Massachusetts, USA
    J Pharmacol Exp Ther 315:812-20. 2005
    ..In conclusion, the gender difference in the inflammatory response shows preferential modulation by PARP in male animals...
  32. ncbi request reprint Role of nitrosative stress and poly(ADP-ribose) polymerase activation in diabetic vascular dysfunction
    Jon G Mabley
    School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building, UK
    Curr Vasc Pharmacol 3:247-52. 2005
    ..This review focuses on the mechanism by which hyperglycaemia induces nitrosative stress and the role PARP activation plays in diabetic vascular dysfunction...
  33. ncbi request reprint Activation of poly(ADP-Ribose) polymerase-1 is a central mechanism of lipopolysaccharide-induced acute lung inflammation
    Lucas Liaudet
    Inotek Corporation, Suite 419 E, 100 Cummings Drive, Beverly, MA 01915, USA
    Am J Respir Crit Care Med 165:372-7. 2002
    ..Our findings support a mechanistic role of PARP-1 in the regulation of LPS-induced lung inflammation. Pharmacological inhibition of PARP may be useful in clinical conditions associated with overwhelming lung inflammation...
  34. ncbi request reprint The role of poly(ADP-ribose) polymerase activation in the development of myocardial and endothelial dysfunction in diabetes
    Pal Pacher
    Inotek Corporation, Beverly, Massachusetts 01915, USA
    Diabetes 51:514-21. 2002
    ..PARP inhibitors may exert beneficial effects against the development of cardiovascular complications in diabetes...
  35. pmc Angiotensin II-mediated endothelial dysfunction: role of poly(ADP-ribose) polymerase activation
    Csaba Szabo
    Inotek Pharmaceuticals Corporation, Suite 419E, 100 Cummings Center, Beverly, MA 01915, USA
    Mol Med 10:28-35. 2004
    ....
  36. ncbi request reprint Activation of poly(ADP-ribose) polymerase contributes to the endothelial dysfunction associated with hypertension and aging
    Pal Pacher
    Inotek Corporation, Suite 419E, 100 Cummings Center, Beverly, MA 01915, USA
    Int J Mol Med 9:659-64. 2002
    ..Thus, PARP activation contributes to the pathogenesis of endothelial dysfunction associated with hypertension and aging, but not in the current experimental model of atherosclerosis...
  37. pmc Endothelial dysfunction in aging animals: the role of poly(ADP-ribose) polymerase activation
    Pal Pacher
    Inotek Corporation, Suite 419E, 100 Cummings Center, Beverly, Massachusetts, MA 01915, USA
    Br J Pharmacol 135:1347-50. 2002
    ..Furthermore, we found no deterioration in the myocardial contractile function in aging animals. Thus, intraendothelial PARP activation may contribute to endothelial dysfunction associated with aging...
  38. ncbi request reprint Pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase may represent a novel therapeutic approach in chronic heart failure
    Pal Pacher
    Inotek Pharmaceuticals Corporation, Beverly, Massachusetts 19105, USA
    J Am Coll Cardiol 40:1006-16. 2002
    ..We investigated the effects of a novel ultrapotent poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, PJ34, on cardiac and endothelial dysfunction in a rat model of chronic heart failure (CHF)...
  39. pmc Poly(ADP-ribose) polymerase is a regulator of chemokine production: relevance for the pathogenesis of shock and inflammation
    Gyorgy Hasko
    Inotek Pharmaceuticals Corporation, Beverly, Massachusetts 01915, USA
    Mol Med 8:283-9. 2002
    ..There is emerging evidence that the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) importantly contributes to the up-regulation of a variety of proinflammatory signal transduction pathways and associated genes...
  40. ncbi request reprint Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents
    Pal Pacher
    Inotek Corporation, Suite 419E, 100 Cummings Center, Beverly, MA 01915, USA
    Biochem Pharmacol 64:1785-91. 2002
    ..Thus, PARP activation in the cardiovascular system is an important contributory factor to the cardiac collapse and death associated with endotoxin shock...
  41. ncbi request reprint Matrix metalloproteinase activation is an early event in doxorubicin-induced cardiotoxicity
    Peter Bai
    Inotek Pharmaceuticals Corporation, 100 Cummings Center, Suite 419E, Beverly, MA 01915, USA
    Oncol Rep 11:505-8. 2004
    ..These results demonstrate that MMP activation is an early event in DOX-induced cardiotoxicity and raises the possibility that MMP inhibitors may influence the outcome of this severe complication...
  42. ncbi request reprint The therapeutic effects of PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide.HCl], a selective inhibitor of poly(ADP-ribose) polymerase, in experimental allergic encephalomyelitis are associated with immunomodulation
    Gwen S Scott
    Department of Microbiology and Immunology, Thomas Jefferson University, JAH 454, 1020 Locust Street, Philadelphia, PA 19107, USA
    J Pharmacol Exp Ther 310:1053-61. 2004
    ..Therefore, the mode of action of PJ34 at the onset of EAE is likely mediated by a shift in the MBP-specific immune response from a proinflammatory Th1 toward an anti-inflammatory Th2 phenotype...