Tideglusib

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Tideglusib
Tideglusib2DACS.svg
Tideglusib-ball-and-stick-model.png
Identifiers
PubChem CID
ChemSpider
Chemical and physical data
Formula C19H14N2O2S
Molar mass 334.392 g/mol
3D model (JSmol)

Tideglusib (NP-12, NP031112) is a potent, selective and irreversible[1] small molecule non-ATP-competitive glycogen synthase kinase 3 (GSK-3) inhibitor.

Potential applications[edit]

Tideglusib is under investigation for multiple applications:

  • Alzheimer's disease and progressive supranuclear palsy. As of 2017 it was undergoing Phase IIa[2] and IIb clinical trials.[3][4][5][6] The first trial to be published (in English) was Phase II and demonstrated that tideglusib was well tolerated, except for some moderate, asymptomatic, fully reversible increases in liver enzymes (≥2.5x ULN; where ULN=Upper Limit of Normal).[4]
  • Tooth repair mechanisms that promotes dentine reinforcement of a sponge structure until the sponge biodegrades, leaving a solid dentine structure. In 2016 it was successfully trialled for permanently filling 0.14mm holes in mouse teeth.[7]
  • Autism spectrum disorders in adolescents.

Furthermore, recent research has shown Tideglusib to be a promising treatment for Congenital/Juvenile-Onset Myotonic Muscular Dystrophy Type I, with Phase II clinical trials (under the aegis of AMO Pharmaceuticals) nearing completion.[8]

References[edit]

  1. ^ Domínguez, JM; Fuertes, A; Orozco, L; del Monte-Millán, M; Delgado, E; Medina, M (January 2012). "Evidence for Irreversible Inhibition of Glycogen Synthase Kinase-3 by Tideglusib" (PDF). The Journal of Biological Chemistry. 287 (2): 893–904. doi:10.1074/jbc.M111.306472. PMC 3256883Freely accessible. PMID 22102280. 
  2. ^ Teodoro Del Ser (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. 
  3. ^ Eldar-Finkelman, H; Martinez, A (2011). "GSK-3 Inhibitors: Preclinical and Clinical Focus on CNS". Frontiers in Molecular Neuroscience. 4: 32. doi:10.3389/fnmol.2011.00032. PMC 3204427Freely accessible. PMID 22065134. 
  4. ^ a b Del Ser, T; Steinwachs, KC; Gertz, HJ; Andrés, MV; Gómez-Carrillo, B; Medina, M; Vericat, JA; Redondo, P; 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. PMID 22936007. 
  5. ^ "FDA Grants Fast Track Status to Tideglusib (ZentylorTM) for Progressive Supranuclear Palsy". PR Newswire Europe Including UK Disclose. 10 September 2010. Retrieved 11 August 2013. 
  6. ^ Dominguez, JM; Fuertes, A; Orozco, L; Del Monte-Millan, M; Delgado, E; Medina, M (2011). "Evidence for Irreversible Inhibition of Glycogen Synthase Kinase-3 by Tideglusib". Journal of Biological Chemistry. 287 (2): 893–904. doi:10.1074/jbc.M111.306472. PMC 3256883Freely accessible. PMID 22102280. 
  7. ^ Gallagher, James (2017-01-09). "'Tooth repair drug' may replace fillings". BBC News. Retrieved 2017-01-09. 
  8. ^ "AMO-2". AMO Pharmaceuticals. Retrieved 2017-09-21.