SB 415286

SKU: orb1300580

Description

SB 415286 is a potent and selective ATP-competitive inhibitor of glycogen synthase kinase-3 (GSK-3), exhibiting IC₅₀ values of 78 nM and 31 nM for GSK-3α and GSK-3β, respectively. This cell-permeable compound is widely used in vitro and in vivo to investigate GSK-3's role in Wnt/β-catenin signaling, neurodegenerative diseases, and glucose metabolism.

Research Area

Cell Biology, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 264218-23-7
• MW: 359.72
• Purity: 99.56%
• Formula: C₁₆H₁₀ClN₃O₅
• SMILES: Oc1ccc(NC2=C(C(=O)NC2=O)c2ccccc2[N+]([O-])=O)cc1Cl
• Target: GSK-3,Apoptosis
• Solubility: DMSO:18 mg/mL (50.04 mM);Ethanol:9 mg/mL (25.02 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.56 mM)

Bioactivity

• Target IC50:
  GSK-3α:78 nM|GSK-3β:31 nM(ki)
• In Vivo:
  Administration of SB 415286 (~10 mg/kg twice daily) reduces the extent and degree of the trinitrobenzene sulphonic acid (TNBS)-provoked colonic inflammation in the rat, and reduces the fall in body weight, which is related to downregulation of NF-κB activity, involved in the generation of proinflammatory mediators. SB 415286 treatment at 1 mg/kg significantly delays the growth of Neuro-2A cells in vivo in nude mice.
• In Vitro:
  SB 415286 inhibits GSK3α in an ATP competitive manner with Ki of 31 nM and shows similar potency against GSK3β. SB 415286 has little or no activity against 24 other protein kinases with IC50 > 10 μ M. SB 415286 stimulates glycogen synthesis in the Chang human liver cell line with EC50 of 2.9 μM, and induces expression of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells. SB 415286 protects both central and peripheral nervous system neurones in culture from death induced by reduced PI3-kinase pathway activity in a concentration-dependent manner, which is correlated with inhibition of GSK-3 activity and modulation of GSK-3 substrates tau and β-catenin. In L6 myotubes, SB 415286 induces a much greater activation of GS (6.8-fold) compared to that elicited by insulin (4.2-fold) or Li (4-fold). SB 415286 (10 μM) inhibits rapamycin-induced down-regulation of cyclin D1, and blocks rapamycin and paclitaxel-induced apoptosis, suggesting a critical role for GSK3β in rapamycin-mediated paclitaxel-sensitization. SB 415286 prevents coxsackievirus-induced cell death in a dose-dependent manner via stabilization of β-catenin. SB 415286 exerts a protective effect on hydrogen peroxide-induced cell death in B65 rat neuroblastoma cells and neurons, while lithium does not attenuate the toxic effects of hydrogen peroxide. SB 415286 treatment potentiates TRAIL- and CH-11-induced apoptosis in HepG2 cells. Inhibition of GSK-3 by SB 415286 causes multiple myeloma (MM) cell growth arrest and apoptosis through the activation of the intrinsic pathway. SB 415286 decreases the viability of Neuro-2A cells, and induces the accumulation of cells in the G2/M phase of the cell cycle and subsequent apoptosis.
• Cell Research:
  Cells are exposed to different concentrations of SB 415286 for 48 or 72 hours in 96-flat well plates. After 48 or 72 hours, [3H]thymidine is added to the cultures (10 μCi/well) for the last 12 hours. The [3H]thymidine incorporation is evaluated by scintillation counting by using a top count β-counter. Apoptosis is assessed by annexin V/Propidium Iodide staining or by detection of mitochondrial membrane potential. Cell death is evaluated by the analysis of Forward/Side scatter fluorescence changes. Fluorescence Activated Cell Sorting (FACS) analysis is performed using a FACS-Calibur Cell Cytometer. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GSK-3α/β, GSK-3, GSK3, Glycogen synthase kinase-3, Glycogen synthase kinase 3, Inhibitor, inhibit, Apoptosis, SB 415286, SB415286, SB-415286

Compound Identifiers

PubChem CID

4210951