Tideglusib (NP-12, NP031112) is a potent and irreversible small molecule

glycogen synthase kinase 3 Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. First discovered in 1980 as a regulatory kinase for its namesake, glycogen s ...

(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, the treatment was discontinued in 35% of all the active subjects, due to such adverse effects (del Ser et al., 2013).

Potential applications

Tideglusib is under investigation for multiple applications: *

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

and

progressive supranuclear palsy Progressive supranuclear palsy (PSP) is a late-onset degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty ...

. Both clinical trials were discontinued in 2011 (PSP) and 2012 (Alzheimer's disease) due to lack of efficacy * Tooth repair mechanisms that promotes

dentine Dentin () (American English) or dentine ( or ) (British English) ( la, substantia eburnea) is a calcified tissue of the body and, along with enamel, cementum, and pulp, is one of the four major components of teeth. It is usually covered by ena ...

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. * Tideglusib is being studied in Phase II clinical trials as a treatment for congenital/juvenile-onset

myotonic muscular dystrophy Myotonic dystrophy (DM) is a type of muscular dystrophy, a group of genetic disorders that cause progressive muscle loss and weakness. In DM, muscles are often unable to relax after contraction. Other manifestations may include cataracts, intell ...

type I.

References

Alzheimer's disease research 1-Naphthyl compounds Thiadiazoles {{nervous-system-drug-stub