Home PI3K/Akt/mTOR GSK-3 inhibitor - Apoptosis related activator SB415286

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SB415286 GSK-3 inhibitor

Cat.No.S2729

SB415286 is a potent GSK3α inhibitor with IC50/Ki of 78 nM/31 nM with equally effective inhibition of GSK-3β. This compound causes MM cell growth arrest and apoptosis.
SB415286 GSK-3 inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 359.72

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: S272901 DMSO]72 mg/mL]false]Ethanol]72 mg/mL]false]Water]Insoluble]false Purity: 99.74%
99.74

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CHO cells Function assay Stimulation of glycogen synthase in CHO cells expressing human insulin receptor, EC50=45.6 μM
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight 359.72 Formula

C16H10ClN3O5

 Storage (From the date of receipt)
CAS No. 264218-23-7 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1=CC=C(C(=C1)C2=C(C(=O)NC2=O)NC3=CC(=C(C=C3)O)Cl)[N+](=O)[O-]

Solubility

In vitro
Batch:

DMSO : 72 mg/mL (200.15 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 72 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
GSK-3α [1]
(Cell-free assay)
78 nM
GSK-3β [1]
(Cell-free assay)
~78 nM
In vitro

SB 415286 inhibits GSK3α in an ATP competitive manner with Ki of 31 nM and shows similar potency against GSK3β. This compound has little or no activity against 24 other protein kinases with IC50 > 10 μ M. It 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. [1] It 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. [2] In L6 myotubes, this chemical induces a much greater activation of GS (6.8-fold) compared to that elicited by insulin (4.2-fold) or Li (4-fold). [3] This compound (10 μM) inhibits rapamycin-induced down-regulation of cyclin D1, and blocks rapamycin and -induced apoptosis, suggesting a critical role for GSK3β in rapamycin-mediated -sensitization. [4] It prevents coxsackievirus-induced cell death in a dose-dependent manner via stabilization of β-catenin. [5] This chemical 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. [7] Its treatment potentiates TRAIL- and CH-11-induced apoptosis in HepG2 cells. [8] Inhibition of GSK-3 by this compound causes multiple myeloma (MM) cell growth arrest and apoptosis through the activation of the intrinsic pathway. [9] It 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. [10]
Kinase Assay
GSK-3 activity assay
GSK-3 kinase activity is measured, in the presence of various concentrations of SB 415286, in a reaction mixture containing final concentrations of: 1 nM human GSK3α or rabbit GSK3α; 50 mM MOPS pH 7.0; 0.2 mM EDTA; 10 mM Mg-acetate; 7.5 mM L-mercaptoethanol; 5% (w/v) glycerol; 0.01% (w/v) Tween-20; 10% (v/v) DMSO; 28 μM GS-2 peptide substrate. The GS-2 peptide sequence corresponds to a region of glycogen synthase that is phosphorylated by GSK-3. The assay is initiated by the addition of 0.34 μCi [33P]γ-ATP (IC50 determinations) or 2.7 μCi [33P]γ-ATP (Ki determinations). The total ATP concentration is 10 μM (IC50 determinations) or ranged from 0 to 45 μM (Ki determinations). Following 30 minutes incubation at room temperature the assay is stopped by the addition of one third assay volume of 2.5% (v/v) H3PO4 containing 21 mM ATP. Samples are spotted onto P30 phosphocellulose mats and these are washed six times in 0.5% (v/v) H3PO4. The filter mats are sealed into sample bags containing Wallac betaplate scintillation fluid. 33P incorporation into the substrate peptide is determined by counting the mats in a Wallac microbeta scintillation counter.
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. [6] Treatment with this compound at 1 mg/kg significantly delays the growth of Neuro-2A cells in vivo in nude mice. [10]
References
  • [4] https://pubmed.ncbi.nlm.nih.gov/15753396/
  • [5] https://pubmed.ncbi.nlm.nih.gov/15905881/
  • [6] https://pubmed.ncbi.nlm.nih.gov/16314851/
  • [7] https://pubmed.ncbi.nlm.nih.gov/18342477/
  • [8] https://pubmed.ncbi.nlm.nih.gov/18938143/
  • [9] https://pubmed.ncbi.nlm.nih.gov/20920357/
  • [10] https://pubmed.ncbi.nlm.nih.gov/21161565/

Applications

Methods Biomarkers Images PMID
Western blot β-catenin / XIAP / Bcl-2 GSK-3β / p53 S2729-WB1 21161565

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