Chemistry:Tideglusib
From HandWiki
Tideglusib (NP-12, NP031112) is a potent and irreversible[1] small molecule glycogen synthase kinase 3 (GSK-3) inhibitor.[2]
Clinical trials
Tideglusib has been evaluated in clinical trials for:
- 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[3][4][5][6][1]
- Congenital/juvenile-onset myotonic muscular dystrophy type I.[7]
Research
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.[8][9]
- Preclinical in vitro studies were carried out for neuroblastoma and ovarian cancer with significant ROS-induced apoptosis.[10][11]
- Arrhythmogenic right ventricular cardiomyopathy as of 2025.[12]
References
- ↑ 1.0 1.1 "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.
- ↑ "GSK-3 Inhibitors: A Double-Edged Sword? - An Update on Tideglusib". Drug Research 68 (8): 436–443. August 2018. doi:10.1055/s-0044-100186. PMID 29388174.
- ↑ "Phase IIa clinical trial on Alzheimer's disease with NP12, a GSK3 inhibitor". Alzheimer's & Dementia 6 (4): S147. 2010. 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): 205–215. 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.
- ↑ "AMO-2". https://www.amo-pharma.com/amo_02.htm.
- ↑ "Promotion of natural tooth repair by small molecule GSK3 antagonists". Scientific Reports 7. January 2017. doi:10.1038/srep39654. PMID 28067250. Bibcode: 2017NatSR...739654N.
- ↑ "'Tooth repair drug' may replace fillings". BBC News. 2017-01-09. https://www.bbc.co.uk/news/uk-38524566.
- ↑ "Correlative Studies Unravelling the Possible Mechanism of Cell Death in Tideglusib-Treated Human Ovarian Teratocarcinoma-Derived PA-1 Cells". Journal of Environmental Pathology, Toxicology and Oncology 36 (4): 321–344. 2017. doi:10.1615/JEnvironPatholToxicolOncol.2017025018. PMID 29431064.
- ↑ "Tideglusib induces apoptosis in human neuroblastoma IMR32 cells, provoking sub-G0/G1 accumulation and ROS generation". Environmental Toxicology and Pharmacology 46: 194–205. September 2016. doi:10.1016/j.etap.2016.07.013. PMID 27490211.
- ↑ "TaRGETed Therapy with Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy". https://www.phri.ca/research/target-2/.
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