Tideglusib

Tideglusib
Identifiers
	IUPAC name 4-Benzyl-2-(naphthalen-1-yl)-1,2,4-thiadiazolidine-3,5-dione;
PubChem CID	11313622;
ChemSpider	9488589;
CompTox Dashboard (EPA)	DTXSID90235682 ;
Chemical and physical data
Formula	C19H14N2O2S
Molar mass	334.392 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C3SN(c1cccc2c1cccc2)C(=O)N3Cc4ccccc4;
	InChI InChI=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;

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

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

^ 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 3256883. PMID 22102280.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ 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.
^ 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 3204427. PMID 22065134.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ ^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.
^ "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.
^ 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 3256883. PMID 22102280.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ Gallagher, James (2017-01-09). "'Tooth repair drug' may replace fillings". BBC News. Retrieved 2017-01-09.
^ "AMO-2". AMO Pharmaceuticals. Retrieved 9/21/2017. {{cite web}}: Check date values in: |accessdate= (help)

This drug article relating to the nervous system is a stub. You can help Wikipedia by expanding it.

[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 3256883. PMID 22102280.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[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 3204427. PMID 22065134.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[trial-4] 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 3256883. PMID 22102280.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[7] Gallagher, James (2017-01-09). "'Tooth repair drug' may replace fillings". BBC News. Retrieved 2017-01-09.

[8] "AMO-2". AMO Pharmaceuticals. Retrieved 9/21/2017. {{cite web}}: Check date values in: |accessdate= (help)

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]