Tideglusib
{{Short description|Chemical compound}}
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{{Drugbox
| drug_name =
| IUPAC_name = 4-Benzyl-2-(naphthalen-1-yl)-1,2,4-thiadiazolidine-3,5-dione
| image = Tideglusib2DACS.svg
| width = 200
| image2 = Tideglusib-ball-and-stick-model.png
| width2 = 200
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| CAS_number = 865854-05-3
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = Q747Y6TT42
| ATCvet =
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| PubChem = 11313622
| ChEBI = 147398
| ChemSpiderID = 9488589
| DrugBank =
| C=19 | H=14 | N=2 | O=2 | S=1
| smiles = O=C3SN(c1cccc2c1cccc2)C(=O)N3Cc4ccccc4
| StdInChI = 1S/C19H14N2O2S/c22-18-20(13-14-7-2-1-3-8-14)19(23)24-21(18)17-12-6-10-15-9-4-5-11-16(15)17/h1-12H,13H2
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Tideglusib (NP-12, NP031112) is a potent and irreversible{{cite journal | vauthors = Domínguez JM, Fuertes A, Orozco L, del Monte-Millán M, Delgado E, Medina M | title = Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib | journal = The Journal of Biological Chemistry | volume = 287 | issue = 2 | pages = 893–904 | date = January 2012 | pmid = 22102280 | pmc = 3256883 | doi = 10.1074/jbc.M111.306472 | doi-access = free }} small molecule glycogen synthase kinase 3 (GSK-3) inhibitor.{{cite journal | vauthors = Mathuram TL, Reece LM, Cherian KM | title = GSK-3 Inhibitors: A Double-Edged Sword? - An Update on Tideglusib | journal = Drug Research | volume = 68 | issue = 8 | pages = 436–443 | date = August 2018 | pmid = 29388174 | doi = 10.1055/s-0044-100186 }}
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{{cite journal | doi = 10.1016/j.jalz.2010.05.455 | title = Phase IIa clinical trial on Alzheimer's disease with NP12, a GSK3 inhibitor | year = 2010 | vauthors = Del Ser T | s2cid = 54293332 | journal = Alzheimer's & Dementia | volume = 6 | issue = 4 | pages = S147}} {{cite journal | vauthors = Eldar-Finkelman H, Martinez A | title = GSK-3 Inhibitors: Preclinical and Clinical Focus on CNS | journal = Frontiers in Molecular Neuroscience | volume = 4 | pages = 32 | year = 2011 | pmid = 22065134 | pmc = 3204427 | doi = 10.3389/fnmol.2011.00032 | doi-access = free }}{{cite journal | vauthors = del Ser T, Steinwachs KC, Gertz HJ, Andrés MV, Gómez-Carrillo B, Medina M, Vericat JA, Redondo P, Fleet D, León T | title = Treatment of Alzheimer's disease with the GSK-3 inhibitor tideglusib: a pilot study | journal = Journal of Alzheimer's Disease | volume = 33 | issue = 1 | pages = 205–215 | year = 2013 | pmid = 22936007 | doi = 10.3233/JAD-2012-120805 | s2cid = 21892732 }}{{cite web | title = FDA Grants Fast Track Status to Tideglusib (ZentylorTM) for Progressive Supranuclear Palsy | url = https://www.prnewswire.com/news-releases/fda-grants-fast-track-status-to-tideglusib-zentylortm-for-progressive-supranuclear-palsy-102561614.html | publisher = PR Newswire Europe Including UK Disclose | date = 10 September 2010 | id = {{ProQuest|750175748}} }}
- Congenital/juvenile-onset myotonic muscular dystrophy type I.{{cite web|title=AMO-2|url=http://www.amo-pharma.com/amo_02.htm|website=AMO Pharmaceuticals|access-date=2017-09-21}}
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.{{cite journal | vauthors = Neves VC, Babb R, Chandrasekaran D, Sharpe PT | title = Promotion of natural tooth repair by small molecule GSK3 antagonists | journal = Scientific Reports | volume = 7 | pages = 39654 | date = January 2017 | pmid = 28067250 | pmc = 5220443 | doi = 10.1038/srep39654 | bibcode = 2017NatSR...739654N }}{{Cite news |url=https://www.bbc.co.uk/news/uk-38524566 |title='Tooth repair drug' may replace fillings | vauthors = Gallagher J |date=2017-01-09 |newspaper=BBC News |access-date=2017-01-09}}
- Preclinical in vitro studies were carried out for neuroblastoma and ovarian cancer with significant ROS-induced apoptosis.{{cite journal | vauthors = Mathuram TL, Ravikumar V, Reece LM, Sasikumar CS, Cherian KM | title = Correlative Studies Unravelling the Possible Mechanism of Cell Death in Tideglusib-Treated Human Ovarian Teratocarcinoma-Derived PA-1 Cells | journal = Journal of Environmental Pathology, Toxicology and Oncology | volume = 36 | issue = 4 | pages = 321–344 | date = 2017 | pmid = 29431064 | doi = 10.1615/JEnvironPatholToxicolOncol.2017025018 }}{{cite journal | vauthors = Mathuram TL, Ravikumar V, Reece LM, Karthik S, Sasikumar CS, Cherian KM | title = Tideglusib induces apoptosis in human neuroblastoma IMR32 cells, provoking sub-G0/G1 accumulation and ROS generation | journal = Environmental Toxicology and Pharmacology | volume = 46 | pages = 194–205 | date = September 2016 | pmid = 27490211 | doi = 10.1016/j.etap.2016.07.013 }}
- Arrhythmogenic Right Ventricular Cardiomyopathy as of 2025.https://www.phri.ca/research/target-2/