Glycogen synthase kinase 3β (GSK3β) is a multifunctional serine/threonine kinase that is a regulator of glycogen metabolism. Obviously, it plays a crucial role in regulating the production of cells, cytoskeletal proteins, and transcription factors, as well as in the transduction of proliferation signals. Particularly, the early interest of GSK3 β as a target of diabetes stems from its potential to regulate blood glucose levels. Importantly, GSK3β is activated through dephosphorylation of serine 9, while Akt is inactivated. Meanwhile, GSK3 plays a core role in the Wnt and β – catenin pathways. The Wnt/β-catenin pathway has been shown to affect hematopoietic stem cells (HSCs) and stem cell characteristics. Nonetheless, GSK3 has been studied as a target for the treatment of many diseases, including diabetes, inflammation, nervous system diseases and recent cancer. Today, we will introduce an irreversible GSK-3 inhibitor for hypoxic-ischemic brain injury research, Tideglusib.

Tideglusib is a GSK3β Inhibitor for Hypoxic-ischemic Brain Injury Research.

Above all, Tideglusib (NP031112) is an irreversible GSK3β inhibitor. Besides, Tideglusib has IC50s of 5 nM and 60 nM for GSK-3βWT and GSK-3βC199A, respectively.

Next in importance, incubation of both astrocyte and microglial cultures with Tideglusib completely abrogates the induction of TNF-α and COX-2 expression after glutamate treatment. Additionally, these effects of NP031112 are not caused by a loss of cell viability, because the 24 h exposure of astrocyte and microglial cells to this TDZD does not modify cell viability.

Once again, Injection of Tideglusib (NP031112) into the rat hippocampus dramatically reduces kainic acid-induced inflammation. However, Tideglusib has a neuroprotective effect in the damaged areas of the hippocampus.

All in all, Tideglusib is an irreversible GSK-3 inhibitor for hypoxic-ischemic brain injury research.


[1] Luna-Medina R, et al. J Neurosci, 2007, 27(21), 5766-5776.