The Experts below are selected from a list of 1344 Experts worldwide ranked by ideXlab platform
Akiko Nakamuraozaki - One of the best experts on this subject based on the ideXlab platform.
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synthesis and reactions of nucleoside 5 diphosphate Imidazolide a nonenzymatic capping agent for 5 monophosphorylated oligoribonucleotides in aqueous solution
Journal of Organic Chemistry, 1999Co-Authors: Hiroaki Sawai, Hiromichi Wakai, Akiko NakamuraozakiAbstract:We have synthesized adenosine and 7-methylguanosine 5‘-diphosphate Imidazolides from imidazole and the corresponding nucleoside 5‘-diphosphates. The phosphorImidazolide bond of the compounds was susceptible to hydrolysis and hydrolyzed gradually in neutral aqueous solution, but it was more stable than that of the corresponding Imidazolides of nucleoside 5‘-monophosphate. The 7-methylguanosine 5‘-diphosphate Imidazolide reacted with guanosine 5‘-monophosphate or 5‘-monophosphorylated oligoribonucleotides in neutral aqueous solution in the presence of an Mn2+ ion catalyst converting to the cap portion of mRNA or the capped m7Gppp-oligoribonucleotides in substantial yields. The condensation reaction of adenosine 5‘-diphosphate Imidazolide with adenosine 5‘-monophosphate took place similarly in neutral aqueous solution by a divalent metal ion-catalyst such as Mg2+ or Mn2+, yielding diadenosine 5‘,5‘-triphosphate.
Michael B. Sporn - One of the best experts on this subject based on the ideXlab platform.
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CDDO-Imidazolide Targets Multiple Amino Acid Residues on the Nrf2 Adaptor, Keap1.
Journal of Medicinal Chemistry, 2020Co-Authors: Xiaoli Meng, J. C. Waddington, Arun Tailor, Adam Lister, Jane Hamlett, Neil G. Berry, B. Kevin Park, Michael B. SpornAbstract:Synthetic triterpenoids including CDDO, its methyl ester (CDDO-Me, bardoxolone methyl), and its Imidazolide (CDDO-Im) enhance Nrf2-mediated antioxidant and anti-inflammatory activity in many diseas...
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ral ssBioMed CentMolecular Cancer
2015Co-Authors: Sung-ho Maeng, Michael B. Sporn, Siegfried JanzAbstract:CDDO-Imidazolide inhibits growth and survival of c-Myc-induced mouse B cell and plasma cell neoplasm
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The Nrf2 triterpenoid activator, CDDO-Imidazolide, protects kidneys from ischemia–reperfusion injury in mice
Kidney International, 2014Co-Authors: Manchang Liu, Narsa M. Reddy, Elizabeth M. Higbee, Haranatha R. Potteti, Sanjeev Noel, Lorraine C. Racusen, Thomas W. Kensler, Michael B. Sporn, Sekhar P. Reddy, Hamid RabbAbstract:Acute kidney injury (AKI) caused by ischemia–reperfusion is a major clinical problem in both native and transplanted kidneys. We had previously shown that deficiency of Nrf2, a potent bZIP transcription factor that binds to the antioxidant response element, enhances susceptibility to experimental ischemic AKI. Here we further explored the role of Nrf2 in AKI by amplifying Nrf2 activation in vivo and in vitro with the synthetic triterpenoid CDDO-Imidazolide. Mice treated with CDDO-Imidazolide and undergoing experimental bilateral ischemic AKI had improved survival and renal function. Treated mice had improved renal histology with a decrease in tubular injury, as well as a decrease in proinflammatory cytokine and chemokine production compared with vehicle-treated mice. In an exploration of protective mechanisms, we found an upregulation of Nrf2 target antioxidant genes in CDDO-Imidazolide-treated mouse kidneys. Furthermore, Nrf2-deficient mice treated with CDDO-Imidazolide had no significant improvement in mortality, renal function or histology, proinflammatory cytokine gene expression, and no significant increase in antioxidant gene expression. In vitro studies demonstrated that the renal epithelial cells were likely an important target of CDDO-Imidazolide. Thus, activation of Nrf2 signaling with CDDO-Imidazolide confers protection from AKI, and presents a new therapeutic opportunity for this common and serious condition.
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the nrf2 triterpenoid activator cddo Imidazolide protects kidneys from ischemia reperfusion injury in mice
Kidney International, 2014Co-Authors: Manchang Liu, Narsa M. Reddy, Elizabeth M. Higbee, Haranatha R. Potteti, Sanjeev Noel, Lorraine C. Racusen, Thomas W. Kensler, Michael B. Sporn, Sekhar P. Reddy, Hamid RabbAbstract:Acute kidney injury (AKI) caused by ischemia–reperfusion is a major clinical problem in both native and transplanted kidneys. We had previously shown that deficiency of Nrf2, a potent bZIP transcription factor that binds to the antioxidant response element, enhances susceptibility to experimental ischemic AKI. Here we further explored the role of Nrf2 in AKI by amplifying Nrf2 activation in vivo and in vitro with the synthetic triterpenoid CDDO-Imidazolide. Mice treated with CDDO-Imidazolide and undergoing experimental bilateral ischemic AKI had improved survival and renal function. Treated mice had improved renal histology with a decrease in tubular injury, as well as a decrease in proinflammatory cytokine and chemokine production compared with vehicle-treated mice. In an exploration of protective mechanisms, we found an upregulation of Nrf2 target antioxidant genes in CDDO-Imidazolide-treated mouse kidneys. Furthermore, Nrf2-deficient mice treated with CDDO-Imidazolide had no significant improvement in mortality, renal function or histology, proinflammatory cytokine gene expression, and no significant increase in antioxidant gene expression. In vitro studies demonstrated that the renal epithelial cells were likely an important target of CDDO-Imidazolide. Thus, activation of Nrf2 signaling with CDDO-Imidazolide confers protection from AKI, and presents a new therapeutic opportunity for this common and serious condition.
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The synthetic triterpenoid CDDO-Imidazolide suppresses STAT phosphorylation and induces apoptosis in myeloma and lung cancer cells.
Clinical cancer research : an official journal of the American Association for Cancer Research, 2006Co-Authors: Karen Liby, Michael B. Sporn, Nga Voong, Charlotte R Williams, Renee Risingsong, Darlene B Royce, Tadashi Honda, Gordon W Gribble, John J LetterioAbstract:Excessive activity of the transcription factors known as signal transducers and activators of transcription (STAT) contributes to the development and progression of malignancy in many organs. It is, therefore, important to develop new drugs to control the STATs, particularly their phosphorylation state, which is required for their transcriptional activity. Myeloma and lung cancer cells were treated with the new synthetic triterpenoid CDDO-Imidazolide, and STAT phosphorylation and apoptosis were evaluated by immunoblotting and fluorescence-activated cell sorting analysis. We now report that CDDO-Imidazolide, previously shown to be a potent agent for control of inflammation, cell proliferation, and apoptosis, rapidly (within 30-60 minutes) and potently (at nanomolar levels) suppresses either constitutive or interleukin-6-induced STAT3 and STAT5 phosphorylation in human myeloma and lung cancer cells. Furthermore, in these cells, CDDO-Imidazolide also up-regulates critical inhibitors of STATs, such as suppressor of cytokine signaling-1 and SH2-containing phosphatase-1 (a tyrosine phosphatase). Moreover, gene array studies reported here show that CDDO-Imidazolide potently regulates the transcription of important genes that are targets of the STATs. Our new data thus show that CDDO-Imidazolide is a potent suppressor of STAT signaling and provide a further mechanistic basis for future clinical use of this agent to control inflammation or cell proliferation.
Hiroaki Sawai - One of the best experts on this subject based on the ideXlab platform.
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synthesis and reactions of nucleoside 5 diphosphate Imidazolide a nonenzymatic capping agent for 5 monophosphorylated oligoribonucleotides in aqueous solution
Journal of Organic Chemistry, 1999Co-Authors: Hiroaki Sawai, Hiromichi Wakai, Akiko NakamuraozakiAbstract:We have synthesized adenosine and 7-methylguanosine 5‘-diphosphate Imidazolides from imidazole and the corresponding nucleoside 5‘-diphosphates. The phosphorImidazolide bond of the compounds was susceptible to hydrolysis and hydrolyzed gradually in neutral aqueous solution, but it was more stable than that of the corresponding Imidazolides of nucleoside 5‘-monophosphate. The 7-methylguanosine 5‘-diphosphate Imidazolide reacted with guanosine 5‘-monophosphate or 5‘-monophosphorylated oligoribonucleotides in neutral aqueous solution in the presence of an Mn2+ ion catalyst converting to the cap portion of mRNA or the capped m7Gppp-oligoribonucleotides in substantial yields. The condensation reaction of adenosine 5‘-diphosphate Imidazolide with adenosine 5‘-monophosphate took place similarly in neutral aqueous solution by a divalent metal ion-catalyst such as Mg2+ or Mn2+, yielding diadenosine 5‘,5‘-triphosphate.
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Synthesis and Reactions of Nucleoside 5‘-Diphosphate Imidazolide. A Nonenzymatic Capping Agent for 5‘-Monophosphorylated Oligoribonucleotides in Aqueous Solution
The Journal of Organic Chemistry, 1999Co-Authors: Hiroaki Sawai, Hiromichi Wakai, Akiko Nakamura-ozakiAbstract:We have synthesized adenosine and 7-methylguanosine 5‘-diphosphate Imidazolides from imidazole and the corresponding nucleoside 5‘-diphosphates. The phosphorImidazolide bond of the compounds was susceptible to hydrolysis and hydrolyzed gradually in neutral aqueous solution, but it was more stable than that of the corresponding Imidazolides of nucleoside 5‘-monophosphate. The 7-methylguanosine 5‘-diphosphate Imidazolide reacted with guanosine 5‘-monophosphate or 5‘-monophosphorylated oligoribonucleotides in neutral aqueous solution in the presence of an Mn2+ ion catalyst converting to the cap portion of mRNA or the capped m7Gppp-oligoribonucleotides in substantial yields. The condensation reaction of adenosine 5‘-diphosphate Imidazolide with adenosine 5‘-monophosphate took place similarly in neutral aqueous solution by a divalent metal ion-catalyst such as Mg2+ or Mn2+, yielding diadenosine 5‘,5‘-triphosphate.
Hamid Rabb - One of the best experts on this subject based on the ideXlab platform.
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The Nrf2 triterpenoid activator, CDDO-Imidazolide, protects kidneys from ischemia–reperfusion injury in mice
Kidney International, 2014Co-Authors: Manchang Liu, Narsa M. Reddy, Elizabeth M. Higbee, Haranatha R. Potteti, Sanjeev Noel, Lorraine C. Racusen, Thomas W. Kensler, Michael B. Sporn, Sekhar P. Reddy, Hamid RabbAbstract:Acute kidney injury (AKI) caused by ischemia–reperfusion is a major clinical problem in both native and transplanted kidneys. We had previously shown that deficiency of Nrf2, a potent bZIP transcription factor that binds to the antioxidant response element, enhances susceptibility to experimental ischemic AKI. Here we further explored the role of Nrf2 in AKI by amplifying Nrf2 activation in vivo and in vitro with the synthetic triterpenoid CDDO-Imidazolide. Mice treated with CDDO-Imidazolide and undergoing experimental bilateral ischemic AKI had improved survival and renal function. Treated mice had improved renal histology with a decrease in tubular injury, as well as a decrease in proinflammatory cytokine and chemokine production compared with vehicle-treated mice. In an exploration of protective mechanisms, we found an upregulation of Nrf2 target antioxidant genes in CDDO-Imidazolide-treated mouse kidneys. Furthermore, Nrf2-deficient mice treated with CDDO-Imidazolide had no significant improvement in mortality, renal function or histology, proinflammatory cytokine gene expression, and no significant increase in antioxidant gene expression. In vitro studies demonstrated that the renal epithelial cells were likely an important target of CDDO-Imidazolide. Thus, activation of Nrf2 signaling with CDDO-Imidazolide confers protection from AKI, and presents a new therapeutic opportunity for this common and serious condition.
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the nrf2 triterpenoid activator cddo Imidazolide protects kidneys from ischemia reperfusion injury in mice
Kidney International, 2014Co-Authors: Manchang Liu, Narsa M. Reddy, Elizabeth M. Higbee, Haranatha R. Potteti, Sanjeev Noel, Lorraine C. Racusen, Thomas W. Kensler, Michael B. Sporn, Sekhar P. Reddy, Hamid RabbAbstract:Acute kidney injury (AKI) caused by ischemia–reperfusion is a major clinical problem in both native and transplanted kidneys. We had previously shown that deficiency of Nrf2, a potent bZIP transcription factor that binds to the antioxidant response element, enhances susceptibility to experimental ischemic AKI. Here we further explored the role of Nrf2 in AKI by amplifying Nrf2 activation in vivo and in vitro with the synthetic triterpenoid CDDO-Imidazolide. Mice treated with CDDO-Imidazolide and undergoing experimental bilateral ischemic AKI had improved survival and renal function. Treated mice had improved renal histology with a decrease in tubular injury, as well as a decrease in proinflammatory cytokine and chemokine production compared with vehicle-treated mice. In an exploration of protective mechanisms, we found an upregulation of Nrf2 target antioxidant genes in CDDO-Imidazolide-treated mouse kidneys. Furthermore, Nrf2-deficient mice treated with CDDO-Imidazolide had no significant improvement in mortality, renal function or histology, proinflammatory cytokine gene expression, and no significant increase in antioxidant gene expression. In vitro studies demonstrated that the renal epithelial cells were likely an important target of CDDO-Imidazolide. Thus, activation of Nrf2 signaling with CDDO-Imidazolide confers protection from AKI, and presents a new therapeutic opportunity for this common and serious condition.
Noel G. Morgan - One of the best experts on this subject based on the ideXlab platform.
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Insulin Secretagogues with an Imidazoline Structure Inhibit Arginine-Induced Glucagon Secretion from Isolated Rat Islets of Langerhans
Biochemical and Biophysical Research Communications, 1997Co-Authors: Mirna Mourtada, Stephen A Smith, Noel G. MorganAbstract:It is well documented that imidazoline compounds such as efaroxan and phentolamine act as potent insulin secretagogues bothin vivoandin vitro,an effect which is mediated principally by blockade of ATP-sensitive potassium channels in the pancreatic B-cell. However, little is known about the effects of these drugs on the secretion of other pancreatic hormones and, in the present work, we have investigated the effects of selective imidazoline compounds on glucagon release from isolated rat islets of Langerhans. None of several imidazoline compounds tested (efaroxan, phentolamine, idazoxan, antazoline) affected glucagon secretion from islets incubated with 4mM glucose. However, when the rate of glucagon release was stimulated by L-arginine (20mM) efaroxan caused a rapid, sustained and dose-dependent inhibition of the secretory response (EC50approximately 30μM). This effect was seen under both static incubation and islet perifusion conditions. Antazoline and phentolamine also inhibited arginine-induced glucagon secretion, whereas idazoxan (an imidazoline which does not affect insulin secretion) failed to alter glucagon release. The inhibitory effects of imidazolines on glucagon release were not secondary to changes in insulin secretion. Taken together, the results indicate that pancreatic A-cells express functional imidazoline receptors which can regulate the secretory activity of the cells.
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the imidazoline i1 receptor agonist moxonidine inhibits insulin secretion from isolated rat islets of langerhans
European Journal of Pharmacology, 1995Co-Authors: Efthymia Tsoli, Susan L F Chan, Noel G. MorganAbstract:Abstract In order to study the pharmacology of the putative imidazoline receptor involved in stimulation of insulin secretion, the potent and selective imidazoline I1 receptor agonist, moxonidine, was employed. Surprisingly, this agent caused a rapid and complete inhibition of glucose-induced insulin secretion in isolated rat islets of Langerhans. This response was reversible upon removal of the compound but was only partially attenuated under conditions of complete α2 blockade, suggesting that it did not derive entirely from the weak α2-adrenoceptor agonist activity of moxonidine. Furthermore, the response could not be attributed to activation of imidazoline I1 receptors since it was not reproduced by a second potent imidazoline I1 receptor agonist, cimetidine, and could not be alleviated by the imidazoline I1 receptor antagonist efaroxan. The results confirm that the imidazoline receptor involved in control of insulin secretion differs from the I1 subclass and suggest that moxonidine inhibits insulin secretion by a mechanism unrelated to imidazoline I1 receptor agonism.
