Tideglusib
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MedKoo CAT#: 522498

CAS#: 865854-05-3

Description: Tideglusib, also known as NP031112, is a GSK-3 inhibitor, which is currently under clinical trial for Alzheimer's disease. Tideglusib protects neural stem cells against NMDA receptor overactivation. Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial. Tideglusib prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders.

Chemical Structure

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Tideglusib
CAS# 865854-05-3
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522498
Name: Tideglusib
CAS#: 865854-05-3
Chemical Formula: C19H14N2O2S
Exact Mass: 334.08
Molecular Weight: 334.393
Elemental Analysis: C, 68.25; H, 4.22; N, 8.38; O, 9.57; S, 9.59

Price and Availability

Size Price Availability Quantity
25mg USD 90 Ready to ship
50mg USD 150 Ready to ship
100mg USD 250 Ready to ship
200mg USD 450 Ready to ship
500mg USD 950 Ready to ship
1g USD 1700 Ready to ship
2g USD 3050 Ready to ship
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Synonym: NP031112; NP 031112; NP-031112; Tideglusib.

IUPAC/Chemical Name: 2-(1-naphthalenyl)-4-(phenylmethyl)-1,2,4-thiadiazolidine-3,5-dione

InChi Key: PMJIHLSCWIDGMD-UHFFFAOYSA-N

InChi Code: 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

SMILES Code: O=C(N1CC2=CC=CC=C2)N(C3=C4C=CC=CC4=CC=C3)SC1=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Irreversible GSK-3 inhibitor with IC50s of 5 nM and 60 nM for GSK-3βWT and GSK-3βC199A, respectively.
In vitro activity: A luciferase reporter containing βRARE sequence was constructed. This reporter was 9-cis-RA inducible in the presence of RXRα, which could be inhibited by overexpression of GSK-3β (Fig.5A). When Ser78 was mutated into Ala78 (RXRα/S78A), GSK-3β-mediated βRARE inhibition could be reactivated by 9-cis-RA (Fig.5A. 9-cis-RA could also restore βRARE activity via GSK-3β inhibition by tideglusib (Fig.5B). Such phenomenon was reproducible in SMMC7721 and Bel-7402 (Fig. S3B and S3C). An investigation was conducted whether GSK-3β could modulate the heterodimeric capacity of RXRα. As expected, 9-cis-RA could induce RXRα interaction with RARα. When overexpression of GSK-3β, 9-cis-RA-induced RXRα:RARα complex was dismantled (Fig.5C and D). Conversely, the complex could be reassembled when GSK-3β was knocked down by specific siRNA (Fig.5D) or inactivated by tideglusib (Fig. 5E, Fig. S3D and S3E). Reference: Theranostics. 2020; 10(3): 1230–1244. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956800/
In vivo activity: Consecutive intravaginal exposure of rabbits to tideglusib for 10 days did not result in significant microscopic abnormalities of vagina tissues. The light microscopy examination revealed intact vaginal epithelium, lack of leukocyte influx and slight vascular congestion in the representative vaginal sections of rabbits receiving gel alone (Fig. 1A) or gel with tideglusib (Fig. 1B). However, ulceration of the epithelial cell layers, vascular congestion, submucosal edema and increased leukocyte infiltration (Fig. 1C) were prominent in N-9 group (a positive control). Accordingly, the total pathological score of tideglusib group (3.4 ± 2.07) was lower than N-9 (7.8 ± 3.82) (p <.05) but not significantly different from negative control (1.4 ± 0.82), as shown in Table 1. Reference: Contracept X. 2019; 1: 100007. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286178/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 14.1 42.20
DMF 1.0 3.00
DMSO PBS (pH 7.2) (1:1) 0.5 1.50

Preparing Stock Solutions

The following data is based on the product molecular weight 334.39 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Armagan G, Keser A, Atalayın Ç, Dagcı T. Tideglusib protects neural stem cells against NMDA receptor overactivation. Pharmacol Rep. 2015 Oct;67(5):823-31. doi: 10.1016/j.pharep.2015.01.007. Epub 2015 Jan 23. PMID: 26398371. 2. Bahmad HF, Chalhoub RM, Harati H, Bou-Gharios J, Assi S, Ballout F, Monzer A, Msheik H, Araji T, Elajami MK, Ghanem P, Chamaa F, Kadara H, Abou-Antoun T, Daoud G, Fares Y, Abou-Kheir W. Tideglusib attenuates growth of neuroblastoma cancer stem/progenitor cells in vitro and in vivo by specifically targeting GSK-3β. Pharmacol Rep. 2021 Feb;73(1):211-226. doi: 10.1007/s43440-020-00162-7. Epub 2020 Oct 8. PMID: 33030673. 3. Wang H, Huang S, Yan K, Fang X, Abussaud A, Martinez A, Sun HS, Feng ZP. Tideglusib, a chemical inhibitor of GSK3β, attenuates hypoxic-ischemic brain injury in neonatal mice. Biochim Biophys Acta. 2016 Oct;1860(10):2076-85. doi: 10.1016/j.bbagen.2016.06.027. Epub 2016 Jul 1. PMID: 27378458. 4. Li J, Ma S, Chen J, Hu K, Li Y, Zhang Z, Su Z, Woodgett JR, Li M, Huang Q. GSK-3β Contributes to Parkinsonian Dopaminergic Neuron Death: Evidence From Conditional Knockout Mice and Tideglusib. Front Mol Neurosci. 2020 Jun 3;13:81. doi: 10.3389/fnmol.2020.00081. PMID: 32581704; PMCID: PMC7283909.
In vitro protocol: 1. Armagan G, Keser A, Atalayın Ç, Dagcı T. Tideglusib protects neural stem cells against NMDA receptor overactivation. Pharmacol Rep. 2015 Oct;67(5):823-31. doi: 10.1016/j.pharep.2015.01.007. Epub 2015 Jan 23. PMID: 26398371. 2. Bahmad HF, Chalhoub RM, Harati H, Bou-Gharios J, Assi S, Ballout F, Monzer A, Msheik H, Araji T, Elajami MK, Ghanem P, Chamaa F, Kadara H, Abou-Antoun T, Daoud G, Fares Y, Abou-Kheir W. Tideglusib attenuates growth of neuroblastoma cancer stem/progenitor cells in vitro and in vivo by specifically targeting GSK-3β. Pharmacol Rep. 2021 Feb;73(1):211-226. doi: 10.1007/s43440-020-00162-7. Epub 2020 Oct 8. PMID: 33030673.
In vivo protocol: 1. Wang H, Huang S, Yan K, Fang X, Abussaud A, Martinez A, Sun HS, Feng ZP. Tideglusib, a chemical inhibitor of GSK3β, attenuates hypoxic-ischemic brain injury in neonatal mice. Biochim Biophys Acta. 2016 Oct;1860(10):2076-85. doi: 10.1016/j.bbagen.2016.06.027. Epub 2016 Jul 1. PMID: 27378458. 2. Li J, Ma S, Chen J, Hu K, Li Y, Zhang Z, Su Z, Woodgett JR, Li M, Huang Q. GSK-3β Contributes to Parkinsonian Dopaminergic Neuron Death: Evidence From Conditional Knockout Mice and Tideglusib. Front Mol Neurosci. 2020 Jun 3;13:81. doi: 10.3389/fnmol.2020.00081. PMID: 32581704; PMCID: PMC7283909.

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1: Koros C, Stamelou M. Interventions in progressive supranuclear palsy. Parkinsonism Relat Disord. 2015 Sep 25. pii: S1353-8020(15)00424-1. doi: 10.1016/j.parkreldis.2015.09.033. [Epub ahead of print] PubMed PMID: 26459661.

2: Sun A, Li C, Chen R, Huang Y, Chen Q, Cui X, Liu H, Thrasher JB, Li B. GSK-3β controls autophagy by modulating LKB1-AMPK pathway in prostate cancer cells. Prostate. 2015 Oct 6. doi: 10.1002/pros.23106. [Epub ahead of print] PubMed PMID: 26440826.

3: Eschlböck S, Krismer F, Wenning GK. Interventional trials in atypical parkinsonism. Parkinsonism Relat Disord. 2015 Sep 25. pii: S1353-8020(15)00429-0. doi: 10.1016/j.parkreldis.2015.09.038. [Epub ahead of print] PubMed PMID: 26421389.

4: Armagan G, Keser A, Atalayın Ç, Dagcı T. Tideglusib protects neural stem cells against NMDA receptor overactivation. Pharmacol Rep. 2015 Oct;67(5):823-31. doi: 10.1016/j.pharep.2015.01.007. Epub 2015 Jan 23. PubMed PMID: 26398371.

5: Poewe W, Mahlknecht P, Krismer F. Therapeutic advances in multiple system atrophy and progressive supranuclear palsy. Mov Disord. 2015 Sep 15;30(11):1528-38. doi: 10.1002/mds.26334. Epub 2015 Jul 30. Review. PubMed PMID: 26227071.

6: Moretti DV. Are there treatments for atypical parkinsonism? An update on actual options. Rev Neurosci. 2015 Oct 1;26(5):547-53. doi: 10.1515/revneuro-2015-0008. PubMed PMID: 26098698.

7: Lovestone S, Boada M, Dubois B, Hüll M, Rinne JO, Huppertz HJ, Calero M, Andrés MV, Gómez-Carrillo B, León T, del Ser T; ARGO investigators. A phase II trial of tideglusib in Alzheimer's disease. J Alzheimers Dis. 2015;45(1):75-88. doi: 10.3233/JAD-141959. PubMed PMID: 25537011.

8: Tolosa E, Litvan I, Höglinger GU, Burn D, Lees A, Andrés MV, Gómez-Carrillo B, León T, Del Ser T; TAUROS Investigators. A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy. Mov Disord. 2014 Apr;29(4):470-8. doi: 10.1002/mds.25824. Epub 2014 Feb 14. PubMed PMID: 24532007.

9: Höglinger GU, Huppertz HJ, Wagenpfeil S, Andrés MV, Belloch V, León T, Del Ser T; TAUROS MRI Investigators. Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial. Mov Disord. 2014 Apr;29(4):479-87. doi: 10.1002/mds.25815. Epub 2014 Jan 31. PubMed PMID: 24488721.

10: Morales-Garcia JA, Luna-Medina R, Alonso-Gil S, Sanz-Sancristobal M, Palomo V, Gil C, Santos A, Martinez A, Perez-Castillo A. Glycogen synthase kinase 3 inhibition promotes adult hippocampal neurogenesis in vitro and in vivo. ACS Chem Neurosci. 2012 Nov 21;3(11):963-71. doi: 10.1021/cn300110c. Epub 2012 Sep 24. PubMed PMID: 23173075; PubMed Central PMCID: PMC3503340.

11: del Ser T, Steinwachs KC, Gertz HJ, Andrés MV, Gómez-Carrillo B, Medina M, Vericat JA, Redondo P, Fleet D, León T. Treatment of Alzheimer's disease with the GSK-3 inhibitor tideglusib: a pilot study. J Alzheimers Dis. 2013;33(1):205-15. doi: 10.3233/JAD-2012-120805. PubMed PMID: 22936007.

12: Domínguez JM, Fuertes A, Orozco L, del Monte-Millán M, Delgado E, Medina M. Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904. doi: 10.1074/jbc.M111.306472. Epub 2011 Nov 18. PubMed PMID: 22102280; PubMed Central PMCID: PMC3256883.

13: Martinez A, Gil C, Perez DI. Glycogen synthase kinase 3 inhibitors in the next horizon for Alzheimer's disease treatment. Int J Alzheimers Dis. 2011;2011:280502. doi: 10.4061/2011/280502. Epub 2011 Jun 30. PubMed PMID: 21760986; PubMed Central PMCID: PMC3132520.

14: Luna-Medina R, Cortes-Canteli M, Sanchez-Galiano S, Morales-Garcia JA, Martinez A, Santos A, Perez-Castillo A. NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders. J Neurosci. 2007 May 23;27(21):5766-76. PubMed PMID: 17522320.