SB216763

ArtNr	S1075-10
Hersteller	Selleckchem
CAS-Nr.	280744-09-4
Menge	10 mg
Quantity options	10 mg 100 mg 1 g 10 g 10 mM/1 mL 5 mg 50 mg 5 g
Kategorie	Oncology Neuroscience Neuroinflammation Metabolism Diabetes Glucose Homeostasis Cholesterol & Lipid Metabolism Molecular Targets for Neuroscience Targets for Rodent Neurosciences Neural Signaling Enzymes Other Fatty Acid Enzymes Inhibitors & Compound Libraries Small Molecules By Organ Lung Cancer Pancreatic Cancer
Typ	Inhibitors
Specific against	other
Smiles	CN1C=C(C2=CC=CC=C21)C3=C(C(=O)NC3=O)C4=C(C=C(C=C4)Cl)Cl
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	GSK-3alpha,GSK-3
Similar products	SB
Lieferbar
Storage Conditions	2 years -80 in solvent
Molecular Weight	371, 22
Administration	Intravenously
Animal Models	C57BL/6N mice with lung inflammation and fibrosis induced by bleomycin (BLM)
Cell lines	BXPC-3, MIA-PaCa2, PANC1, ASPC1, and CFPAC cells
Concentrations	Dissolved in DMSO, final concentrations ca.50 uM
Dosages	20 mg/kg
Formulation	Dissolved in DMSO, and diluted in saline
IC50	34.3 nM [1], 34.3 nM [1], 34.3 nM [1], 34.3 nM [1], 34.3 nM [1], 34.3 nM [1]
In vitro	SB 216763 displays similar potency for GSK-3beta with 96% inhibition at 10 uM while exhibiting minimal activity against 24 other protein kinases including PKBalpha and PDK1 with IC50 of >10 uM. SB 216763 stimulates glycogen synthesis in human liver cells with EC50 of 3.6 uM, and induces dose-dependent transcription of a beta-catenin-LEF/TCF regulated reporter gene in HEK293 cells with a maximum 2.5-fold induction at 5 uM. [1] SB 216763 protects the cerebellar granule neurones from apoptotic cell death induced by LY-294002 or potassium-deprivation in a concentration-dependent manner, with a maximal neuroprotection at 3 uM in contrast with the effect of lithium chloride at which 10 mM is required. SB 216763 at 3 uM also completely prevents death of chicken dorsal root ganglion sensory neurones induced by LY-294002 regardless of NGF. SB 216763 treatment at 5 uM markedly inhibits the GSK-3-dependent phosphorylation of neuronal-specific microtubule-associated protein tau in cerebellar granule neurones or recombinant tau in HEK293 cells, and induces increased levels of cytoplasmic beta-catenin in both cells mimicking the effect of Wnt-mediated inhibition of GSK-3. [2] In pancreatic cancer cell lines including BXPC-3, MIA-PaCa2, PANC1, ASPC1, and CFPAC, SB 216763 treatment at 25-50 uM reduces cell viability in a dose-dependent manner, and leads to significant increase in apoptosis by 50% at 72 hours due to the specific down regulation of GSK-3beta, while has no effect in HMEC or WI38 cell lines. [3]
In vivo	Administration of SB 216763 at 20 mg/kg significantly prevents lung inflammation and the subsequent fibrosis in bleomycin (BLM)-induced pulmonary inflammation and fibrosis model in mice by significantly blocking the production of inflammatory cytokines MCP-1 and TNF-alpha by macrophages, and significantly improves the survival of BLM-treated mice. SB 216763 treatment causes a significant reduction in BLM-induced alveolitis by inhibiting alveolar epithelial cell damage. [4]
Incubation Time	24, 48, and 72 hours
Kinase Assay	GSK-3 activity assay, GSK-3 kinase activity is measured, in the presence of various concentrations of SB 216763, in a reaction mixture containing final concentrations of 1 nM human GSK-3alpha, 50 mM MOPS pH 7.0, 0.2 mM EDTA, 10 mM Mg-acetate, 7.5 mM beta-mercaptoethanol, 5% (w/v) glycerol, 0.01% (w/v) Tween-20, 10% (v/v) DMSO, and 28 uM 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 uCi [33P]gamma-ATP. The total ATP concentration is 10 uM. 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 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.
Method	Cells are exposed to various concentrations of SB 216763 for 24, 48 and 72 hours. Relative cell viability is measured using the MTS assay. Apoptotic cells are determined by staining with Hoechst.
Solubility (25C)	DMSO 23 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Information	SB216763 is a potent and selective GSK-3 inhibitor with IC50 of 34.3 nM for GSK-3α and equally effective at inhibiting human GSK-3β. SB216763 activates autophagy.
Chemical Name	3-(2, 4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2, 5-dione

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