High purity SB216763 powder CAS 280744‑09‑4 GSK‑3α/GSK‑3β inhibitor Wnt β‑catenin pathway activator biochemical raw material

SB216763 CAS 280744‑09‑4 High‑Purity Powder Selective GSK‑3α/GSK‑3β Inhibitor Wnt‑Pathway Biochemical Reagent

High‑purity SB216763 powder CAS 280744‑09‑4 (chemical name:3‑(2,4‑dichlorophenyl)‑4‑(1‑methyl‑1H‑indol‑3‑yl)‑1H‑pyrrole‑2,5‑dione) is a potent, cell‑permeable and ATP‑competitive dual‑selective inhibitor for GSK‑3α and GSK‑3β isozymes. This pale‑yellow crystalline small‑molecule compound activates the Wnt/β‑catenin signalling pathway, shields nerve‑cell from apoptosis and sustains the pluripotency of embryonic stem‑cells. It is widely used in laboratory research including neural‑protection, tumour‑cell‑apoptosis testing, pulmonary‑fibrosis study, cardiac‑renal‑injury experiment and stem‑cell‑culture exploration. Every batch completes strict HPLC purity inspection, bulk‑order service and customizable‑packaging are available for global biochemistry and pharmacology‑research clients.

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SB216763 (CAS 280744-09-4) GSK-3 Inhibitor | ATP-Competitive GSK-3α/β Inhibitor, Wnt/β-Catenin Activator

SB216763 CAS 280744-09-4
Potent ATP-Competitive GSK-3α/β Inhibitor

A cell-permeable maleimide-class small molecule that inhibits glycogen synthase kinase-3 (GSK-3α and GSK-3β) with an IC50 of approximately 34 nM. SB216763 is the reference chemical tool for stabilizing β-catenin, activating Wnt/β-catenin transcription, reducing tau hyperphosphorylation, driving stem cell self-renewal, and stimulating glycogen synthesis. Structurally related to SB415286 and highly selective across the wider kinome.

GSK-3α/β Inhibitor ATP-Competitive Cell-Permeable Wnt/β-Catenin Activator Tau Research Stem Cell Self-Renewal Neuroprotective
Request a Quote Technical Specs
371.22
MW (C19H12Cl2N2O2)
~34 nM
IC50 vs GSK-3
≥98%
Purity (HPLC)

Molecular Information

Name: SB216763
CAS: 280744-09-4
Formula: C19H12Cl2N2O2
MW: 371.22 g/mol
Purity: ≥98% (HPLC)
SMILES: Clc1ccc(c(Cl)c1)
  C1=C(C(=O)NC1=O)
  c1cn(C)c2ccccc12
InChIKey: JCSGFHVFHSKIJH
  -UHFFFAOYSA-N
Appearance: Orange to red-orange
  crystalline powder
Solubility: DMSO (≥20 mg/mL)
Target: GSK-3α / GSK-3β
Storage: -20°C, desiccated, dark
🧪
CAS Number
280744-09-4
⚖️
Molecular Weight
371.22
🎯
Primary Target
GSK-3α/β
✅
Purity
≥98%

SB216763 Technical Specifications & QC Parameters

Complete physicochemical data and quality-control profile for research-grade SB216763 (CAS 280744-09-4)

📋 Physicochemical Properties

  • Product NameSB216763
  • IUPAC Name3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
  • CAS Number280744-09-4
  • SynonymsSB 216763 / GSK-3 Inhibitor XV
  • Molecular FormulaC19H12Cl2N2O2
  • Molecular Weight371.22 g/mol
  • Exact Mass370.027 Da
  • SMILESClc1ccc(c(Cl)c1)C1=C(C(=O)NC1=O)c1cn(C)c2ccccc12
  • InChIKeyJCSGFHVFHSKIJH-UHFFFAOYSA-N
  • AppearanceOrange to red-orange crystalline powder
  • Melting Point287-289°C (lit.)
  • Chemical ClassArylindolylmaleimide
  • MDL NumberMFCD09753369
  • Related AnalogueSB415286

🔬 Quality Control & Handling

  • Purity (HPLC)≥98%
  • FormCrystalline powder
  • Biological PotencyIC50 ≈ 34 nM (GSK-3); Ki ≈ 9 nM; ATP-competitive
  • Kinase Selectivity>10 µM against 24 other protein kinases
  • Cellular ActivityEC50 ≈ 3.6 µM (glycogen synthesis, Chang liver cells)
  • SolubilityDMSO ≥20 mg/mL (~54 mM); insoluble in water
  • Storage Condition-20°C, desiccated, protect from light
  • Stock Solution Storage-20°C to -80°C, aliquoted, avoid freeze-thaw
  • QC DocumentationCOA / HPLC / NMR / MS / MSDS
  • Pack Sizes1g / 5g / 10g / 100g / 1KG
  • Stock StatusIn Stock
  • Use StatementResearch use only; not for human or clinical use

Molecular Targets & Downstream Signalling Nodes

SB216763 occupies the ATP pocket of both GSK-3 isoforms, which propagates through a dense network of substrates controlling metabolism, transcription, cytoskeletal stability and cell fate

🎯 GSK-3α (GSK3A) 🎯 GSK-3β (GSK3B) 🧬 β-Catenin (CTNNB1) 🧠 Tau (MAPT) 🍬 Glycogen Synthase (GYS1) 🔁 Axin / APC Destruction Complex 📜 TCF/LEF Transcription 🧷 Cyclin D1 🔂 c-Myc ⚡ eIF2B 🛡️ Mitochondrial PTP 🔥 NF-κB / CREB Crosstalk

SB216763 Mechanism of Action: From ATP Pocket to Wnt Output

How a single ATP-competitive binding event converts into β-catenin stabilization, tau dephosphorylation and metabolic reprogramming

1

ATP-Competitive Binding

The dichlorophenyl-indolylmaleimide scaffold inserts into the highly conserved ATP-binding cleft of GSK-3α and GSK-3β, hydrogen-bonding to the hinge region and displacing ATP with nanomolar affinity (IC50 ≈ 34 nM, Ki ≈ 9 nM).

2

Loss of Substrate Phosphorylation

With catalysis blocked, GSK-3 can no longer phosphorylate its priming-dependent substrates: β-catenin (Ser33/37/Thr41), tau (Ser396/404, Thr231), glycogen synthase (site 3a-c), eIF2B, cyclin D1 and c-Myc.

3

β-Catenin Escapes Degradation

Unphosphorylated β-catenin is not recognised by β-TrCP, so it evades ubiquitination and proteasomal destruction. Cytosolic β-catenin accumulates within 1-4 hours of treatment in most cell types.

4

Wnt/β-Catenin Transcription

Stabilized β-catenin enters the nucleus, displaces Groucho from TCF/LEF and switches on the canonical Wnt programme (AXIN2, LGR5, CCND1, MYC) — a pharmacological mimic of Wnt3a ligand stimulation.

5

Tau Dephosphorylation & Neuroprotection

Reduced tau phosphorylation at GSK-3-dependent epitopes limits paired-helical-filament formation, restores microtubule binding, and protects primary neurons from PI3K-inhibition or trophic-withdrawal induced apoptosis.

6

Metabolic & Cytoprotective Output

Dephosphorylated glycogen synthase becomes active, increasing glycogen synthesis independently of insulin, while GSK-3 inhibition raises the threshold for mitochondrial permeability-transition-pore opening — the basis of GSK-3-mediated cardioprotection.

Research Applications of the GSK-3 Inhibitor SB216763

From Alzheimer's tau pathology to pluripotent stem cell culture, SB216763 is a workhorse probe wherever GSK-3 sits at the centre of the pathway

🧠

Alzheimer's Disease & Tau Pathology

GSK-3β is the principal tau kinase generating hyperphosphorylated tau in neurofibrillary tangles. SB216763 lowers phospho-tau at Ser396/404 and Thr231 in neuronal cultures and transgenic models, making it a standard positive control in tau-directed drug discovery and neurodegeneration research.

Neurodegeneration
🧬

Wnt/β-Catenin Signalling Activation

Used as a small-molecule Wnt agonist to stabilize β-catenin and drive TCF/LEF reporter activity (TOPflash) without recombinant Wnt ligand. Ideal for developmental biology, organoid patterning, and dissecting canonical versus non-canonical Wnt outputs.

Wnt Agonist
🌱

Stem Cell Self-Renewal & Pluripotency

GSK-3 inhibition is one half of the classic "2i" ground-state condition for mouse embryonic stem cells. SB216763 sustains pluripotency marker expression (Oct4, Nanog, Sox2), supports clonal survival, and is applied in iPSC reprogramming, cardiomyocyte differentiation and intestinal organoid protocols.

Stem Cell Biology
🍬

Insulin Signalling & Glucose Metabolism

Relieves inhibitory phosphorylation of glycogen synthase and suppresses hepatic gluconeogenic gene expression (G6Pase, PEPCK), increasing glycogen deposition in liver and skeletal muscle cells. A key tool in type 2 diabetes and insulin-resistance research.

Metabolic Research
🔬

Cancer Biology & Tumour Signalling

GSK-3 acts as a context-dependent tumour suppressor or promoter. SB216763 is used to interrogate β-catenin-driven proliferation, cyclin D1/c-Myc turnover, NF-κB survival signalling in pancreatic and leukaemic cells, and GSK-3 dependence in MLL-rearranged leukaemia.

Oncology
🧘

Mood Disorders & Lithium-Mimetic Biology

Because lithium's therapeutic action is partly attributed to GSK-3 inhibition, SB216763 serves as a selective pharmacological surrogate to test the GSK-3 hypothesis of bipolar disorder and depression in behavioural paradigms and circadian rhythm studies.

Psychiatry
❤️

Cardioprotection & Ischemia-Reperfusion

GSK-3β inhibition at reperfusion desensitizes the mitochondrial permeability transition pore and limits infarct size. SB216763 is widely used in Langendorff-perfused heart and cardiomyocyte hypoxia/reoxygenation models of ischemic conditioning.

Cardiovascular
🦴

Bone, Fibrosis & Regeneration

Canonical Wnt activation promotes osteoblast differentiation and bone formation, while GSK-3 modulation influences fibroblast activation and wound repair. SB216763 supports osteogenesis, chondrogenesis and tissue-regeneration studies.

Regenerative Medicine
🛡️

Inflammation & Immune Modulation

GSK-3 inhibition shifts the CREB/NF-κB balance in monocytes and macrophages, reducing IL-6, IL-12 and TNF-α while raising IL-10. SB216763 is applied in innate-immunity, sepsis and neuroinflammation (microglia) models.

Immunology

Key Publications Citing SB216763

Foundational papers on the discovery, selectivity and biological application of this GSK-3 inhibitor

Coghlan MP, Culbert AA, Cross DAE, et al. Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chemistry & Biology. 2000;7(10):793-803. [Original discovery of SB216763 and SB415286]
doi: 10.1016/S1074-5521(00)00025-9
Cross DAE, Culbert AA, Chalmers KA, et al. Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death. Journal of Neurochemistry. 2001;77(1):94-102.
doi: 10.1046/j.1471-4159.2001.t01-1-00251.x
Lochhead PA, Coghlan M, Rice SQJ, Sutherland C. Inhibition of GSK-3 selectively reduces glucose-6-phosphatase and phosphoenolpyruvate carboxykinase gene expression. Diabetes. 2001;50(5):937-946.
doi: 10.2337/diabetes.50.5.937
Bain J, Plater L, Elliott M, et al. The selectivity of protein kinase inhibitors: a further update. Biochemical Journal. 2007;408(3):297-315. [Kinome-wide selectivity profiling]
doi: 10.1042/BJ20070797
Kirby LA, Schott JT, Noble BL, et al. Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells. PLoS ONE. 2012;7(6):e39329.
doi: 10.1371/journal.pone.0039329
Carmichael J, Sugars KL, Bao YP, Rubinsztein DC. Glycogen synthase kinase-3β inhibitors prevent cellular polyglutamine toxicity caused by the Huntington's disease mutation. Journal of Biological Chemistry. 2002;277(37):33791-33798.
doi: 10.1074/jbc.M204861200

SB216763 Pack Sizes & Ordering Information

Research-grade SB216763 (CAS 280744-09-4) supplied with full QC documentation — available in 1g / 5g / 10g / 100g / 1KG

TierPack SizeStock StatusTypical Use CaseShipping Notes
Standard1 gIn StockEnzyme assays, cell-based Wnt reporter screens, dose-response workSame/next-day dispatch; ambient shipping, foil pouch
Medium5 gIn StockPrimary neuron and stem cell culture, multi-week in vitro programmesSame/next-day dispatch; desiccant included
Large10 gIn StockRodent in vivo pharmacology, multi-lab collaborations, HTS libraries1-2 business days; amber container, light-protected
Bulk100 gIn StockFormulation development, large animal cohorts, process R&DQuote to confirm; double-bagged HDPE drum, cool shipping option
Industrial1 KGMade to orderPilot-scale synthesis, CRO/CMO supply agreements, contract manufacturingBatch delivery on campaign schedule; export documents and COA per lot

💡 Reference pack sizes shown above; for current pricing, lot availability and bulk SB216763 quotations please contact us for a quote. Tiered discounts apply to 100 g and 1 KG orders.

SB216763 Frequently Asked Questions (FAQ)

What is SB216763 and why is it so widely used?
SB216763 is a cell-permeable, ATP-competitive inhibitor of glycogen synthase kinase-3 built on an arylindolylmaleimide scaffold (C19H12Cl2N2O2, MW 371.22). It inhibits GSK-3 with an IC50 of roughly 34 nM while showing no meaningful activity against 24 other protein kinases at 10 µM. That combination of nanomolar potency, cell permeability, chemical stability and clean selectivity has made it the default GSK-3 tool compound in Wnt signalling, tau biology, stem cell culture and metabolic research since its publication in Chemistry & Biology in 2000.
Is SB216763 selective for GSK-3α or GSK-3β?
It inhibits both isoforms essentially equally. The original IC50 of 34.3 nM was measured against human GSK-3α, and the compound produced comparable inhibition of GSK-3β in parallel assays. This is expected: GSK-3α and GSK-3β share ~98% sequence identity in their kinase domains, so ATP-site binders rarely discriminate between them. If you need isoform-specific conclusions, combine SB216763 with genetic approaches such as isoform-selective siRNA or knock-in kinase-dead alleles.
How does SB216763 activate Wnt/β-catenin signalling?
GSK-3 is the catalytic engine of the β-catenin destruction complex (Axin–APC–CK1α–GSK-3). Blocking GSK-3 prevents phosphorylation of β-catenin at Ser33, Ser37 and Thr41, the phosphodegron recognised by the β-TrCP E3 ligase. β-catenin therefore escapes ubiquitination, accumulates in the cytosol, enters the nucleus and converts TCF/LEF factors from repressors to activators — reproducing the transcriptional signature of Wnt3a treatment (AXIN2, LGR5, CCND1, MYC induction) without any recombinant ligand.
Does SB216763 cross the blood-brain barrier?
SB216763 is a small, lipophilic, non-charged maleimide, and central effects have been reported after systemic dosing in rodent studies of tau phosphorylation, neuroprotection, cerebral ischaemia and behavioural despair — consistent with brain penetration. Reported brain exposure is nonetheless modest and strongly vehicle-dependent, so many groups either use DMSO/PEG-based intraperitoneal formulations or deliver the compound directly by intracerebroventricular or intrathecal injection when high, sustained central target engagement is essential. Always verify target engagement with a phospho-substrate readout such as phospho-glycogen synthase or phospho-tau in your own model.
How does SB216763 compare with lithium?
Lithium is an indirect, low-affinity GSK-3 inhibitor that works largely by competing with Mg2+ and requires millimolar concentrations; at those concentrations it also inhibits inositol monophosphatase, IMPase-family phosphomonoesterases and other Mg2+-dependent enzymes, so lithium phenotypes cannot be cleanly attributed to GSK-3. SB216763 is a direct, ATP-competitive inhibitor active in the nanomolar range with a defined selectivity profile. For mechanistic work, SB216763 is the more rigorous choice; lithium remains useful as a clinically anchored comparator.
How does SB216763 differ from SB415286 and CHIR99021?
SB415286 is the anilinomaleimide sister compound from the same GlaxoSmithKline programme (IC50 ≈ 78 nM) and is somewhat more water-tolerant. CHIR99021 is an aminopyrimidine with higher potency (IC50 in the low nanomolar range) and is the GSK-3 inhibitor used in the canonical "2i" stem cell medium. SB216763 sits between them: potent, very well characterised in the literature, cheaper at scale, and with a decade-plus of comparative data — which is why it is often chosen as the reference GSK-3 inhibitor for orthogonal confirmation.
What concentrations of SB216763 are typically used?
Typical cell culture concentrations range from 1-20 µM, with 3-10 µM being the most common working window for β-catenin stabilization and phospho-substrate readouts; the reported cellular EC50 for stimulating glycogen synthesis in Chang liver cells is about 3.6 µM. Biochemical kinase assays use nanomolar concentrations. For rodent studies, published intraperitoneal doses commonly fall in the 0.2-10 mg/kg range depending on model and vehicle. Always run a dose-response and include a vehicle-matched DMSO control.
How should I prepare and store SB216763 solutions?
Dissolve in DMSO to make a concentrated stock (≥20 mg/mL, roughly 54 mM, is achievable; 10-50 mM stocks are typical). Warm briefly to 37 °C and vortex if needed. Dilute into aqueous medium immediately before use and keep the final DMSO ≤0.1% v/v for most cell types. Store the solid at -20 °C, desiccated and protected from light; store aliquoted DMSO stocks at -20 °C (short term) or -80 °C (long term) and avoid repeated freeze-thaw cycles. Because SB216763 is a coloured maleimide, avoid prolonged exposure to strong light and to thiol-rich buffers.
What controls should I include when using SB216763?
Best practice is to (1) include a vehicle-only DMSO control at matched concentration; (2) confirm target engagement by immunoblotting for phospho-glycogen synthase (Ser641), phospho-β-catenin (Ser33/37/Thr41) or total β-catenin; (3) confirm the phenotype with a structurally unrelated GSK-3 inhibitor such as CHIR99021 or SB415286; and (4) where possible, corroborate with genetic GSK-3 knockdown or a β-catenin-dependent TCF/LEF reporter (TOPflash/FOPflash) pair.
What QC documentation is supplied, and can I order bulk quantities?
Every lot ships with a Certificate of Analysis (COA) including HPLC purity (≥98%), 1H NMR structural confirmation and MS identity data; MSDS/SDS, solubility datasheets and Certificates of Origin are available on request. Pack sizes run from 1 g through 5 g, 10 g, 100 g and 1 KG, with the 1 KG tier produced to order on a campaign basis. For custom purity specifications, alternative packaging or repeat-supply agreements, please contact our technical sales team.

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