title: Thienylhalomethylketones: Irreversible glycogen synthase kinase 3 inhibitors as useful pharmacological tools.
abstract: Thienylhalomethylketones, whose chemical, biological, and pharmaceutical data are here reported, are the first irreversible inhibitors of GSK-3beta described to date. Their inhibitory activity is likely related to the cysteine residue present in the ATP-binding site, which is proposed as a relevant residue for modulation of GSK-3 activity. The good cell permeability of the compounds allows them to be used in different cell models. Overall, the results presented here support the potential use of halomethylketones as pharmacological tools for the study of GSK-3beta functions and suggest a new mechanism for GSK-3beta inhibition that may be considered for further drug design.
authors.affiliation: Instituto de Química Médica-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Perez
authors.forename: Santiago
authors.initials: S
authors.lastname: Conde
authors.forename: Concepción
authors.initials: C
authors.lastname: Pérez
authors.forename: Carmen
authors.initials: C
authors.lastname: Gil
authors.forename: Diana
authors.initials: D
authors.lastname: Simon
authors.forename: Francisco
authors.initials: F
authors.lastname: Wandosell
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Moreno
authors.forename: José L
authors.initials: JL
authors.lastname: Gelpí
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Luque
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez
mesh_terms: D000818:Animals; D001665:Binding Sites; D002463:Cell Membrane Permeability; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D007659:Ketones; D047428:Protein Kinase Inhibitors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3