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2000
Volume 10, Issue 12
  • ISSN: 1389-5575
  • E-ISSN: 1875-5607

Abstract

Glycogen Phosphorylase (GP) is an important target for the development of anti-hyperglycaemic drugs. GP is an enzyme which is moderated allosterically with multiple ligand binding sites where inhibitors can potentially modulate enzyme activity. The search for potent and isoform selective inhibitors of GP is ongoing with an increasing focus on allosteric inhibition. In this review, the structural diversity, and enzyme interactions of the most recent inhibitors, and in particular allosteric inhibitors, of GP at the different key binding sites are explored. A range of inhibitors of GP, with known as well as unknown binding site or mechanism is presented.

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/content/journals/mrmc/10.2174/138955710793177340
2010-10-01
2025-12-14
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  • Article Type:
    Research Article
Keyword(s): 23-hydroxybetulinic acid derivatives; 3,4-dichlorophenyl moiety; 5-benzylidene-thiazolidine-2,4-diones; 6-chloroindole moiety; allos-teric indole site; allosteric activator; allosteric indole inhibitors; allosteric inhibition; allosteric regulation; amide linker; AMP-allosteric site; anti-hyperglycaemic drugs; antitumour drugs; aspartic acid; Bayer diacid; benzamide derivatives; blood glucose levels; C-alkanoyl glycosides; channel of GP; chlorobenzamide; CP-320,626; CP-526,423; dephosphorylation; facile aminolysis reaction; flavones; flavopiridol; gallic acid; GlaxoSmithKline; glucose-1-phosphate; glucose-6-phosphate; glycogen metabolism; Glycogen phosphorylase; glycogen storage site; glycogen-associated protein phosphatase 1; glycogenolysis; GP molecule; Heterocyclic amides; heterocyclic scaffold; human brain glycogen phosphorylase; human liver glycogen phosphorylase; human muscle glycogen phosphorylase; hy-drophobic pocket; indirubin derivatives; inhibitor; isoenzymes; liver X receptor; matched molecular pair analysis; naphthalene moiety; non-indole compounds; OH group; oleanolic acid; pentacyclic triterpenoids maslinic acid; phenyl diacid; phosphate binding site; phosphate recognition site; phosphorylase kinase; phosphorylation; phosphorylation state; protein phosphatase 1; PURINE NUCLEOSIDE SITE INHIBITORS; purine site inhibitors; pyridoxal-5'-phosphate (PLP); rHLGPa; RMGPb-asiatic acid; structure activity relation-ship; structure based drug design; thalidomide; thieno[2,3-b]pyrrole group; Thieno[2,3-b]pyrroles; van der Waals interac-tions; Waals interactions
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