title: Famotidine inhibits glycogen synthase kinase-3β: an investigation by docking simulation and experimental validation.
abstract: Famotidine was investigated as an inhibitor of glycogen synthase kinase-3β (GSK-3β) in an attempt to explain the molecular mechanism of its hypoglycemic side effects. The investigation included simulated docking experiments, in vitro enzyme inhibition assay, glycogen sparing studies using animal models and single dose oral glucose tolerance test (OGTT). Docking studies showed how famotidine is optimally fit within the binding pocket of GSK-3β via numerous attractive interactions with some specific amino acids. Experimentally, famotidine could inhibit GSK-3β (IC₅₀ = 1.44 μM) and increased significantly liver glycogen spares in fasting animal models. Moreover, a single oral dose of famotidine was shown to decrease the glycemic response curve after 75 g OGTT.
authors.affiliation: Faculty of Pharmacy, University of Jordan, Amman 11942, Jordan. mkmohammad@ju.edu.jo
authors.forename: Mohammad
authors.initials: M
authors.lastname: Mohammad
authors.forename: Ihab M
authors.initials: IM
authors.lastname: Al-Masri
authors.forename: Ala
authors.initials: A
authors.lastname: Issa
authors.forename: Mohamed A S
authors.initials: MA
authors.lastname: Al-Ghussein
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fararjeh
authors.forename: Hatim
authors.initials: H
authors.lastname: Alkhatib
authors.forename: Mutasem O
authors.initials: MO
authors.lastname: Taha
authors.forename: Yasser
authors.initials: Y
authors.lastname: Bustanji
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D015738:Famotidine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000032:analysis; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D015738:Famotidine; D006003:Glycogen; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3