tideglusib   Click here for help

GtoPdb Ligand ID: 6929

Synonyms: NP031112
Compound class: Synthetic organic
Comment: Tideglusib is a small molecule non-ATP-competitive, irreversible glycogen synthase kinase 3 (GSK-3β) inhibitor [2] that has been investigated as a potential treatment for Alzheimer's disease and paralysis supranuclear palsy [4]. Low-dose tideglusib has been reported to induce natural reparative dentine formation, as a novel approach to treating tooth decay [5].

In vitro and in vivo, tideglusib (and analogues) has shown anti-staphylococcal activity, via inhibition of Staphylococcus aureus sortase A (SrtA; a virulence factor of Gram-positive pathogens) [6].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 2
Hydrogen bond donors 0
Rotatable bonds 3
Topological polar surface area 71.72
Molecular weight 334.08
XLogP 4.07
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES O=c1sn(c(=O)n1Cc1ccccc1)c1cccc2c1cccc2
Isomeric SMILES O=c1sn(c(=O)n1Cc1ccccc1)c1cccc2c1cccc2
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
InChI Key PMJIHLSCWIDGMD-UHFFFAOYSA-N
References
1. del Ser T, Steinwachs KC, Gertz HJ, Andrés MV, Gómez-Carrillo B, Medina M, Vericat JA, Redondo P, Fleet D, León T. (2013)
Treatment of Alzheimer's disease with the GSK-3 inhibitor tideglusib: a pilot study.
J Alzheimers Dis, 33 (1): 205-15. [PMID:22936007]
2. Domínguez JM, Fuertes A, Orozco L, del Monte-Millán M, Delgado E, Medina M. (2012)
Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib.
J Biol Chem, 287 (2): 893-904. [PMID:22102280]
3. Luna-Medina R, Cortes-Canteli M, Sanchez-Galiano S, Morales-Garcia JA, Martinez A, Santos A, Perez-Castillo A. (2007)
NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders.
J Neurosci, 27 (21): 5766-76. [PMID:17522320]
4. Martinez A, Gil C, Perez DI. (2011)
Glycogen synthase kinase 3 inhibitors in the next horizon for Alzheimer's disease treatment.
Int J Alzheimers Dis, 2011: 280502. [PMID:21760986]
5. Neves VC, Babb R, Chandrasekaran D, Sharpe PT. (2017)
Promotion of natural tooth repair by small molecule GSK3 antagonists.
Sci Rep, 7: 39654. [PMID:28067250]
6. Yang T, Zhang T, Guan XN, Dong Z, Lan L, Yang S, Yang CG. (2020)
Tideglusib and Its Analogues As Inhibitors of Staphylococcus aureus SrtA.
J Med Chem, 63 (15): 8442-8457. [PMID:32639734]