tideglusib

Description: Tideglusib (formerly known as NP031112, NP12) is a novel, potent, irreversible, non-ATP-competitive and chemical inhibitor of GSK-3beta (glycogen synthase kinase-3beta) with potential neuroprotective effects and may be used as an anti-AD (Alzheimer disease) agent. It inhibits GSK-3beta with an IC50 of 60 nM in cell-free assay; Tideglusib is currently undergoing phase II clinical trials for Alzheimer disease and progressive supranuclear palsy. Tideglusib inhibits GSK-3beta irreversibly, as shown by the lack of recovery in enzyme function after the unbound Tideglusib was removed from the reaction medium; Also, its dissociation rate constant is non-significantly different from zero. In addition, tideglusib failed to inhibit a variety of kinases that contain a Cys homologous to Cys-199 in their active site, suggesting that its inhibition of GSK-3beta obeys to a specific mechanism and is not a consequence of nonspecific reactivity.

References: J Biol Chem. 2012 Jan 6; 287(2):893-904; J Neurosci. 2007 May 23; 27(21):5766-76.