Chemistry:Tideglusib
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| Formula | C19H14N2O2S |
| Molar mass | 334.39 g·mol−1 |
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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:
- Alzheimer's disease and progressive supranuclear palsy. Both clinical trials were discontinued in 2011 (PSP) and 2012 (Alzheimer's disease) due to lack of efficacy[2] [3][4][5][6]
- 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]
References
- ↑ "Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib". The Journal of Biological Chemistry 287 (2): 893–904. January 2012. doi:10.1074/jbc.M111.306472. PMID 22102280.
- ↑ Del Ser, Teodoro (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.
- ↑ "GSK-3 Inhibitors: Preclinical and Clinical Focus on CNS". Frontiers in Molecular Neuroscience 4: 32. 2011. doi:10.3389/fnmol.2011.00032. PMID 22065134.
- ↑ "Treatment of Alzheimer's disease with the GSK-3 inhibitor tideglusib: a pilot study". Journal of Alzheimer's Disease 33 (1): 205–15. 2013. doi:10.3233/JAD-2012-120805. PMID 22936007.
- ↑ "FDA Grants Fast Track Status to Tideglusib (ZentylorTM) for Progressive Supranuclear Palsy". PR Newswire Europe Including UK Disclose. 10 September 2010. https://www.prnewswire.com/news-releases/fda-grants-fast-track-status-to-tideglusib-zentylortm-for-progressive-supranuclear-palsy-102561614.html.
- ↑ "Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib". The Journal of Biological Chemistry 287 (2): 893–904. January 2012. doi:10.1074/jbc.M111.306472. PMID 22102280.
- ↑ "Promotion of natural tooth repair by small molecule GSK3 antagonists". Scientific Reports 7: 39654. January 2017. doi:10.1038/srep39654. PMID 28067250. Bibcode: 2017NatSR...739654N.
- ↑ Gallagher, James (2017-01-09). "'Tooth repair drug' may replace fillings". BBC News. https://www.bbc.co.uk/news/uk-38524566.
- ↑ "AMO-2". http://www.amo-pharma.com/amo_02.htm.
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