Tideglusib (CAS 865854-05-3) GSK-3β Inhibitor | Irreversible Non-ATP-Competitive, Alzheimer's & Wnt/β-Catenin Research Compound

Tideglusib CAS 865854-05-3
Irreversible, Non-ATP-Competitive GSK-3β Inhibitor (NP-031112 / NP-12)

Tideglusib (CAS 865854-05-3), also NP-031112 / NP-12, is an irreversible, non-ATP-competitive inhibitor of glycogen synthase kinase-3 beta (GSK-3β) with an IC50 of ~5 nM (WT) that covalently targets Cys199. It reduces tau phosphorylation and activates Wnt/β-catenin. Molecular formula C19H14N2O2S, MW 334.4. Research-grade with COA.

GSK-3β Tideglusib NP-031112 Tau Phosphorylation Wnt/β-catenin Alzheimer's Neuroprotection TDZD

Request a Quote Technical Specs

334.4

MW (C19H14N2O2S)

~5 nM

GSK-3β IC50

Irreversible

Cys199 covalent

Molecular Information

Name: Tideglusib
CAS: 865854-05-3
Formula: C19H14N2O2S
MW: 334.4 g/mol
Class: Thiadiazolidinedione (TDZD)
Core: 4-benzyl-2-(naphthalen-1-yl)-1,2,4-thiadiazolidine-3,5-dione
Target: GSK-3β
IC50: ~5 nM (WT)
MP: 148-150 C
Appearance: White to off-white solid
Synonyms: NP-031112 / NP-12
Storage: -20 C

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CAS Number

865854-05-3

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Molecular Weight

334.4

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Primary Activity

GSK-3β Inhibitor

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Purity

≥98%

Product Technical Specifications

Complete physicochemical properties and QC parameters for Tideglusib (CAS 865854-05-3)

📋 Physicochemical Properties

Product NameTideglusib
IUPAC Core4-benzyl-2-(naphthalen-1-yl)-1,2,4-thiadiazolidine-3,5-dione
CAS Number865854-05-3
SynonymsNP-031112; NP-12; NP031112
Molecular FormulaC19H14N2O2S
Molecular Weight334.4 g/mol
SourceSynthetic small molecule (Zeltia / Noscira)
AppearanceWhite to off-white solid
Melting Point148-150 C
Water SolubilityLow (sparingly soluble)
Organic SolubilityDMSO; DMSO/organic vehicle
Compound ClassThiadiazolidinedione / irreversible GSK-3β inhibitor
HS Code2934.99

🔬 Quality Control & Handling

Purity (HPLC)≥98%
FormSolid powder
Primary TargetGSK-3β (glycogen synthase kinase 3 beta)
Pathway ReadoutReduced p-GSK-3 substrates (tau); ↑ β-catenin / AXIN2; Wnt activation
SelectivityNon-ATP-competitive; irreversible (Cys199 covalent)
Storage Condition-20 C, sealed, protect from light
Solution StabilityAliquot DMSO stocks; avoid freeze-thaw
ShippingBlue ice / cold chain recommended
QC DocumentationCOA / HPLC / NMR / MS / MSDS
Pack Sizes1g / 5g / 10g / 100g / 1KG
Stock StatusIn Stock
Use StatementResearch use only; not for human/clinical use

Key Molecular Targets & Pathway Nodes

Tideglusib's primary node is GSK-3β, a serine/threonine kinase positioned at the intersection of tau pathology, Wnt signaling and apoptosis — but its non-ATP, covalent mechanism is unusual.

🧬 GSK-3β (GSK3B) 🧬 GSK-3α 🧱 Tau Protein (p-Tau) 🔗 Wnt/β-Catenin 🧱 AXIN2 🧱 APC / Destruction Complex 🧠 Amyloid-β Production 🛡️ Apoptosis Pathways 🔥 NF-κB / Inflammatory 🦴 Osteogenesis 🧬 Glycogen Synthase ⚡ Cys199 Active-Site Covalent

How Tideglusib Works: Covalent, Non-ATP GSK-3β Blockade

Tideglusib locks GSK-3β irreversibly by covalently modifying Cys199, so target engagement outlasts plasma exposure

Non-ATP-Competitive, Covalent Binding

Unlike typical kinase inhibitors that compete for ATP, tideglusib enters the GSK-3β active site and forms a covalent bond with Cys199. The dissociation rate (koff) is near zero, so inhibition is irreversible and sustained even after plasma clearance.

Reduced Tau Phosphorylation & Neuroprotection

GSK-3β is the major tau kinase; its blockade lowers pathologic tau hyperphosphorylation and reduces apoptotic death in neurons and neuroblastoma models. This underpins tideglusib's interest in Alzheimer's and tauopathy research.

Wnt/β-Catenin Activation

By inhibiting GSK-3β within the destruction complex, tideglusib stabilizes β-catenin and drives Wnt target-gene transcription (e.g., AXIN2). This makes it a potent Wnt activator — used in regenerative, odontogenic and osteogenic studies, and a contrast to ATP-competitive inhibitors like CHIR99021.

⚖️ Tideglusib vs CHIR99021 vs Lithium

Tideglusib (this product)GSK-3β IC50 ~5 nM; irreversible, non-ATP (Cys199)
CHIR99021ATP-competitive GSK-3 inhibitor; reversible
LithiumWeak, non-selective GSK-3 inhibitor; high mM
Shared TargetAll inhibit GSK-3β / β-catenin pathway
Key DistinctionTideglusib is covalent & sustained
Wnt ActivationTideglusib ~7.5x stronger AXIN2 induction than CHIR99021 in hDPSCs

♻️ Downstream Biological Consequences

KinaseGSK-3β activity abolished (covalent)
CytoskeletonReduced tau hyperphosphorylation
TranscriptionStabilized β-catenin; ↑ AXIN2
Wnt OutputEnhanced Wnt/β-catenin signaling
Cell FateNeuroprotection; osteo-/odontogenic differentiation
InflammationAttenuated glial TNF-α / COX-2

Research Applications & Models

From tau-pathology research to a standout Wnt activator, tideglusib bridges neurodegeneration and regenerative biology.

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Alzheimer's & Tauopathy Models

A leading irreversible GSK-3β inhibitor for reducing tau phosphorylation and probing tau-pathology mechanisms in neuronal and transgenic models.

GSK-3β / Tau

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Wnt/β-Catenin & Regeneration

Potent Wnt activator used in bone, dental-pulp (hDPSCs) and tissue-regeneration studies where β-catenin stabilization drives differentiation.

Wnt / β-catenin

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Neuroprotection

Studied for glutamate-excitotoxicity and apoptotic protection in cortical neurons, astrocytes and microglia.

Neuroprotection

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Inflammation & Glia

Investigated for suppression of glial activation (TNF-α, COX-2) in neuroinflammatory models.

Glia / Inflammation

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GSK-3 Biology

A fiducial covalent GSK-3β probe distinguishing ATP-competitive vs non-ATP, irreversible mechanisms.

Kinase mechanism

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Osteogenesis & Development

Used to dissect GSK-3/ Wnt roles in developmental and skeletal biology.

Development

Key Literature & Landmark Publications

The enzymology, irreversibility and clinical translation of tideglusib.

Domínguez JM, et al. Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. J Biol Chem. 2012;287(2):893-904.

doi: 10.1074/jbc.M111.314781

Lovestone S, et al. A phase II trial of tideglusib in Alzheimer's disease. J Alzheimers Dis. 2015;45(1):75-88.

doi: 10.3233/JAD-141659

Selleck / kinase profile: tideglusib irreversibly inhibits GSK-3 (IC50 60 nM, cell-free).

Landmark reference

del Ser T, et al. Tideglusib, a GSK-3 inhibitor, in progressive supranuclear palsy. (Phase II).

Landmark reference

Medina M, et al. GSK-3β and tau: tideglusib mechanism in neurodegeneration. (Review).

Landmark reference

Available Sizes & Ordering

Research-grade Tideglusib (CAS 865854-05-3) with full QC documentation; standard packs and bulk custom quantities supported.

Tier	Pack Size	Stock Status	Suitable For	Lead Time
Standard	1g	In Stock	GSK-3β / tau & Wnt assays	Cold chain
Medium	5g	In Stock	Neurodegeneration & regeneration models	Cold chain
Large	10g	In Stock	Long-term in vivo & formulation studies	Cold chain
Bulk	100g	In Stock	Formulation & process development	Quote to confirm
Industrial	1KG	Made to order	Pilot/production scale, CMO supply	Batch delivery

💡 Reference sizes shown above; for exact pricing and availability please contact us for a quote. Bulk orders qualify for tiered discounts.

Frequently Asked Questions (FAQ)

What is tideglusib and what does it do?

Tideglusib (CAS 865854-05-3), also NP-031112 / NP-12, is an irreversible, non-ATP-competitive inhibitor of GSK-3β (IC50 ~5 nM, wild-type; ~60 nM in cell-free kinase assay). It covalently modifies Cys199 in the active site, reducing tau phosphorylation and activating Wnt/β-catenin. Formula C19H14N2O2S, MW 334.4.

How is tideglusib different from CHIR99021 or lithium?

CHIR99021 and lithium are reversible, ATP-competitive (or non-selective) GSK-3 inhibitors, whereas tideglusib binds covalently and irreversibly. Because its koff is near zero, target engagement persists long after plasma clearance — enabling sustained pathway modulation with infrequent dosing. Tideglusib also induces AXIN2 ~7.5x more strongly than CHIR99021 in dental-pulp stem cells.

What is the mechanism in Alzheimer's / tau research?

GSK-3β is the principal tau kinase; hyperactive GSK-3β drives pathologic tau phosphorylation in tauopathies. Tideglusib blocks this, lowering p-tau and protecting neurons from apoptosis, which is why it advanced to Phase II trials in Alzheimer's disease and progressive supranuclear palsy.

What are the key experimental readouts?

Readouts include tau phosphorylation (AT8/AT270 Western), β-catenin stabilization and AXIN2 mRNA (qPCR) for Wnt activation, GSK-3 activity assays, and neuroprotection/apoptosis endpoints. Because binding is covalent, target engagement can be confirmed by washout-resistant inhibition.

How soluble is tideglusib and how should it be prepared?

Tideglusib is soluble in DMSO but sparingly water-soluble. For cell assays prepare a concentrated DMSO stock and dilute into medium (final DMSO <=0.1% v/v); for in vivo use validated vehicles (e.g., corn oil, DMSO mixes). Store the solid at -20 C, desiccated and protected from light; aliquot stocks.

Is QC documentation provided?

Every batch ships with a Certificate of Analysis (COA) including HPLC purity, NMR structural confirmation and MS data. MSDS/SDS and Certificates of Origin are available on request. Sample evaluation is available for qualified institutions — please contact us.

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