|   |  2017 Aug;34(4):563-574. doi: 10.1007/s10719-017-9776-5. 2016 Jan 27;108:444-454. doi: 10.1016/j.ejmech.2015.12.004. 2003;9(15):1177-89. doi: 10.2174/1381612033454919.  |  3,5,6-tricarboxylate~W1807! Glycogen Phosphorylase Inhibitor | C17H15ClF2N4O4 | CID 10070301 - structure, chemical names, physical and chemical properties, classification, patents, literature, biological activities, safety/hazards/toxicity information, supplier lists, and more. Kun S, Bokor É, Sipos Á, Docsa T, Somsák L. Molecules. Crystallographic studies indicate, however, that selectivity between glycogen phosphorylase in skeletal muscle and liver is unlikely to be achieved. The design of glycogen phosphorylase (GP) inhibitors targeting the catalytic site of the enzyme is a promising strategy for a better control of hyperglycaemia in the context of type 2 diabetes. Goyard D, Kónya B, Chajistamatiou AS, Chrysina ED, Leroy J, Balzarin S, Tournier M, Tousch D, Petit P, Duret C, Maurel P, Somsák L, Docsa T, Gergely P, Praly JP, Azay-Milhau J, Vidal S. Eur J Med Chem. Selleck's CP-91149 has been cited by 3 publications Cells, 2020, 9 (3) J Biol Chem, 2020, 295 (1):83-98 A glucopyranosyl urea compound that acts as an inhibitor of muscle glycogen phosphorylase (K i = 930 nM). USA.gov. Reduces blood glucose levels and increases hepatic glycogen content in C57/BL6J mice. Please enable it to take advantage of the complete set of features! CP-91149 is a selective glycogen phosphorylase (GP) inhibitor with IC50 of 0.13 μM in the presence of glucose, 5- to 10-fold less potent in the absence of glucose. Revisiting Glycogen in Cancer: A Conspicuous and Targetable Enabler of Malignant Transformation. HHS 2010 Oct;10(12):1102-26. Mavreas KF, Neofytos DD, Chrysina ED, Venturini A, Gimisis T. Molecules. Activation of glycogen phosphorylase and phosphorolysis of glycogen: The active form of glycogen phosphorylase kinase phosphorylates and activates glycogen phosphorylase. 2020 Nov 22;25(22):5463. doi: 10.3390/molecules25225463. 2018 Mar 15;23(3):666. doi: 10.3390/molecules23030666. 2020 Oct 30;10:592455. doi: 10.3389/fonc.2020.592455. 2010 Oct;10(12):1139-55. doi: 10.2174/1389557511009011139. Front Oncol. glycogen phosphorylase glycogen debranching enzyme phosphoglucomutase Glycogen phosphorylase (phosphorylase) - phosphorolysis of glucose residues at least 5 units from branch point Glycogen + Pi glycogen + glucose-1-phosphate (n residues) (n-1 residues) homodimer of 842-residues (92-kD) subunits allosteric regulation - inhibitors (ATP, glucose-6- The present survey is focused on recent new molecules, potential inhibitors of the enzyme. 2008 Apr;9(4):379-95. Glycogen phosphorylase inhibitor N-(3,5-dimethyl-Benzoyl)-N′-(β-D-glucopyranosyl)urea improves glucose tolerance under normoglycemic and diabetic conditions and rearranges hepatic metabolism. Progress in our understanding of the mechanism of action of these inhibitors has been made by the determination of high-resolution enzyme inhibitor structures (both muscle and liver). Fischer T, Koulas SM, Tsagkarakou AS, Kyriakis E, Stravodimos GA, Skamnaki VT, Liggri PGV, Zographos SE, Riedl R, Leonidas DD. Glycogen Phosphorylase Inhibitor is a cell-permeable urea compound that acts as a potent and AMP-competitive inhibitor of PYGB (glycogen phosphorylase); IC 50 = 53 nM). Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Inhibition of glycogen phosphorylase in the context of type 2 diabetes, with focus on recent inhibitors bound at the active site. In the Search of Glycoside-Based Molecules as Antidiabetic Agents. Rath VL, Ammirati M, Danley DE, Ekstrom JL, Gibbs EM, Hynes TR, Mathiowetz AM, McPherson RK, Olson TV, Treadway JL, Hoover DJ. CAS Number 648926-15-2. COVID-19 is an emerging, rapidly evolving situation. Cholic acid/7-aza-indole conjugates are promising in vivo drug delivery systems to the liver. Another set of patents disclose cholic acid/7-aza-indole conjugates for targeted drug delivery to the liver. USA.gov. A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover Gerald A. Dienel, Kelly K. Ball and Nancy F. Cruz Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA Abstract Displays a mixed type of inhibition. Glycogen phosphorylase (GP) catalyzes the hydrolysis of glycogen to generate glucose-1-phosphate and shortened glycogen molecule and is considered the rate limiting step in the degradation of glycogen. Active Inhibitor 1 protein and direct phosphorylation by cAMP-dependent protein kinase keep protein phosphatase 1 in the inactive state so that is does not remove the activating phosphate group from glycogen phosphorylase. When glucose concentrations get too high, phosphorylase a is converted to its inactive, T state. NLM Design of potent GP inhibitors is a therapeutic strategy in the context of type 2 diabetes. Glycogen phosphorylase (GP) catalyzes the breakdown of glycogen and largely contributes to hepatic glucose production making GP inhibition an attractive target to … 2, 3, 4 Computation as a tool for glycogen phosphorylase inhibitor design. Stathi A, Mamais M, Chrysina ED, Gimisis T. Molecules. Probing the catalytic site of rabbit muscle glycogen phosphorylase using a series of specifically modified maltohexaose derivatives. Glucose-based inhibitors have found potential applications since they now reach low nanomolar Ki values. Glycogen metabolism has implications in beta cell function. Top Curr Chem (Cham). Increasing doses (50–100 μ M) of the glycogen phosphorylase inhibitor CP-320626 inhibited [1,2-13C2]glucose stable isotope substrate re-distribution among glycolysis, pentose and … 1 It blocks glucagon-induced hepatic glycogenolysis in vivo.  |  Areas covered: Glucose-based inhibitors have found potential applications since they now reach low nanomolar Ki values. Hence, the search for potent and selective inhibitors of this enzyme, which may lead to antihyperglycaemic drugs, has received particular attention. Glycogen phosphorylase (GP) is the key enzyme for glycogen degradation. Approximately 90 – 95% of all diabetes mellitus diagnoses are classified as type 2 / non-insulin dependant diabetes mellitus (NIDDM).1 Currently in Australia, diabetes 2019 Apr 3;24(7):1322. doi: 10.3390/molecules24071322. The protein glycogen phosphorylase has been linked to type 2 diabetes, indicating the importance of this target to human health. to form the phosphorylated This substance, [R- (R*,S*)]-5-chloro- N - [3- (dimethylamino)-2-hydroxy-3-oxo-1- (phenylmethyl)propyl]-1H-indole-2-carboxamide (CP-91149), inhibited HLGPa with an IC 50 of 0.13 μM in the presence of 7.5 mM glucose. Advances in glycogen phosphorylase inhibitor design. Such inhibitors may be of use for therapy of the non-insulin dependent form of diabetes (NIDDM or Type II diabetes). Nagy L, Béke F, Juhász L, Kovács T, Juhász-Tóth É, Docsa T, Tóth A, Gergely P, Somsák L, Bai P. PLoS One. Mini Rev Med Chem. Keywords: Since glucose production in the liver has been shown to increase in type 2 diabetes patients, inhibiting the release of glucose from the liver's glycogen's supplies appears to be a valid approach. eCollection 2020. Synthesis, Kinetic and Conformational Studies of 2-Substituted-5-(β-d-glucopyranosyl)-pyrimidin-4-ones as Potential Inhibitors of Glycogen Phosphorylase. Curr Opin Investig Drugs. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Mavreas KF, Neofytos DD, Chrysina ED, Venturini A, Gimisis T. Molecules. 2008 Apr;9(4):379-95. Glycogen phosphorylase inhibitor is a cell-permeable acyl urea first identified as an inhibitor of human liver glycogen phosphorylase (IC 50 = 53 nM). Clipboard, Search History, and several other advanced features are temporarily unavailable. 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