Thienylhalomethylketones: Irreversible glycogen synthase kinase 3 inhibitors as useful pharmacological tools

TitleThienylhalomethylketones: Irreversible glycogen synthase kinase 3 inhibitors as useful pharmacological tools
Publication TypeJournal Article
Year of Publication2009
AuthorsPerez, DI, Conde S, Perez C, Gil C, Simon D, Wandosell F, Moreno FJ, Gelpi JL, Luque FJ, Martinez A
JournalBioorganic & medicinal chemistry
Volume17
Issue19
Pagination6914 - 6925
Date Published2009/10/01/
Keywords&, 3/antagonists, Animals;, Binding, Cell, Glycogen, Humans;, Inhibitors/chemical, inhibitors;, Ketones/chemical, Kinase, Membrane, Permeability;, Protein, Relationship, Sites;, Structure-Activity, Synthase, synthesis/pharmacology;
AbstractThienylhalomethylketones, 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.