SB 415286

Names

[ Name ]:
SB 415286

[Synonym ]:
1H-Pyrrole-2,5-dione, 3-[(3-chloro-4-hydroxyphenyl)amino]-4-(2-nitrophenyl)-
3-[(3-Chloro-4-hydroxyphenyl)amino]-4-(2-nitrophenyl)-1H-pyrrol-2,5-dione
Tocris-1617
3-(3-chloro-4-hydroxyphenylamino)-4-(2-nitrophenyl)-1H-pyrrole-2,5-dione
3-[(3-Chloro-4-hydroxyphenyl)amino]-4-(2-nitrophenyl)-1H-pyrrole-2,5-dione
MFCD04039789
SB 415286

Biological Activity

[Description]:

SB 415286 is a potent and selective cell permeable inhibitor of GSK-3α, with an IC50 of 77.5 nM, and a Ki of 30.75 nM; SB 415286 is equally effective at inhibiting human GSK-3α and GSK-3β.

[Related Catalog]:

Signaling Pathways >> PI3K/Akt/mTOR >> GSK-3

Signaling Pathways >> Stem Cell/Wnt >> GSK-3

Research Areas >> Metabolic Disease

[Target]

hGSK-3α:77.5 nM (IC50)

hGSK-3β:77.5 nM (IC50)

[In Vitro]

SB 415286 (SB-415286) inhibits human GSK-3α with an IC50 of 77.5 nM, and a Ki of 30.75 nM. SB-415286 stimulates glycogen synthesis in the Chang human liver cell line with EC50 of 2.9 μM. SB-415286 stimulates glycogen synthase activity in Chang human liver cells. SB-415286 induces transcription of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells[1]. SB 415286 (SB-415286, 5-44 μM) attenuates B65 cell loss mediated by 1 mM H2O2. SB-415286 (5-44 μM) causes a significant dose-dependent decrease in the fluorescence intensity of DCF, and attenuates B65 ROS production as mediated by 1 mM H2O2. SB-415286 (5-44 μM) also attenuates ROS production in CGN mediated by 1 mM H2O2[2]. SB-415286 (50 µM) induces a substantial suppression of immunoprecipitated GSK3 activity by 97%[3].

[Kinase Assay]

GSK-3 kinase activity is measured, in the presence or absence of SB-216763 or SB-415286, in a reaction mixture containing final concentrations of: 1 nM human GSK-3α or rabbit GSK3α; 50 mM MOPS pH 7.0; 0.2 mM EDTA; 10 mM Mg-acetate; 7.5 mM β-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 ranges from 0 to 45 μM (Ki determinations). Following 30 min 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[1].

[Cell Assay]

B65 cells are used after 24 h of in vitro culture. CGN are used after 7-8 days in vitro. Lithium and SB-415286 are dissolved in culture media and DMSO, respectively, and added to the neuronal preparation at the precise concentrations, 1 h before addition H2O2 (50 μM to 1 mM). To assess the loss in cell viability, we use the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium] method. MTT is added to the cells at a final concentration of 250 μM and incubated for 1 h, allowing the reduction in MTT to produce a dark blue formazan product. Media are then removed, and cells are dissolved in dimethylsulfoxide. Formazan production is measured by the absorbency change at 595 nm using a microplate reader. Viability results are expressed as percentages. The absorbency measured from non-treated cells is taken to be 100%[2].

[References]

[1]. Coghlan MP, et al. Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol. 2000 Oct;7(10):793-803.

[2]. Pizarro JG, et al. Neuroprotective effects of SB-415286 on hydrogen peroxide-induced cell death in B65 rat neuroblastoma cells and neurons. Int J Dev Neurosci. 2008 May-Jun;26(3-4):269-76.

[3]. MacAulay K, et al. Use of lithium and SB-415286 to explore the role of glycogen synthase kinase-3 in the regulation of glucose transport and glycogen synthase. Eur J Biochem. 2003 Sep;270(18):3829-38.

[Related Small Molecules]

CHIR-99021 (CT99021) | SB216763 | TWS119 | LY2090314 | Tideglusib | BIO | Kenpaullone | AR-A014418 | AZD1080 | CHIR-98014 | AZD2858 | Indirubin-3'-monoxime | Bikinin | RGB-286638 | TDZD-8

Chemical & Physical Properties

[ Density]:
1.6±0.1 g/cm3

[ Boiling Point ]:
595.8±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₆H₁₀ClN₃O₅

[ Molecular Weight ]:
359.721

[ Flash Point ]:
314.1±30.1 °C

[ Exact Mass ]:
359.030884

[ PSA ]:
124.25000

[ LogP ]:
2.06

[ Appearance of Characters ]:
yellow to orange

[ Vapour Pressure ]:
0.0±1.7 mmHg at 25°C

[ Index of Refraction ]:
1.746

[ Storage condition ]:
−20°C

[ Water Solubility ]:
DMSO: 16 mg/mL

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
S26-S36

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

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