Tideglusib (NP-12, NP031112) is a potent and irreversible[1] small molecule
glycogen synthase kinase 3 (GSK-3) inhibitor.
Other GSK inhibitors
There are few classes of GSK-inhibitors, including lithium
(Martinez et al., 2011), the small peptide L803mts10, and members
of the thiazolidinedione family, containing inhibitors of GSK-3, such as TDZD-8 (Shapira et al., 2007) or
Tideglusib® (Noscira, Madrid, and Spain), the latter having an
irreversible inhibitory effect on GSK-3 (Dominguez et al., 2012). The
inhibition of the GSK-3 pathways through distinct mechanisms has
been associated with a wide range of adverse reactions, ranging
from mild, such as vertigo—or diarrhea (del Ser et al., 2013)—to
very severe, such as hypoglycemia—or tumorigenesis (Martinez
et al., 2011). The use of Tideglusib specifically was associated with
mild-moderate adverse reactions, which included transient increases
in serum creatine kinase, ALT—or gGT—diarrhea, nausea, cough,
fatigue, and headache (del Ser et al., 2013). In a phase-IIa clinical
trial for Alzheimer's disease, the treatment was discontinued,
due to lack of efficacy (del Ser et al., 2013).
Potential applications
Tideglusib is or has been under investigation for multiple applications:
Tooth repair mechanisms that promotes
dentine reinforcement of a sponge structure until the sponge biodegrades, leaving a solid dentine structure. In 2016, the results of animal studies were reported in which 0.14 mm holes in mouse teeth were permanently filled.[7][8]
nothing is being studied in Phase II clinical trials as a treatment for congenital/juvenile-onset
myotonic muscular dystrophy type I.[9]
^Del Ser T (2010). "Phase IIa clinical trial on Alzheimer's disease with NP12, a GSK3 inhibitor". Alzheimer's & Dementia. 6 (4): S147.
doi:
10.1016/j.jalz.2010.05.455.
S2CID54293332.
^del Ser T, Steinwachs KC, Gertz HJ, Andrés MV, Gómez-Carrillo B, Medina M, et al. (2013). "Treatment of Alzheimer's disease with the GSK-3 inhibitor tideglusib: a pilot study". Journal of Alzheimer's Disease. 33 (1): 205–15.
doi:
10.3233/JAD-2012-120805.
PMID22936007.
S2CID21892732.