SB216763

Catalog No.S1075 Batch:S107501

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Technical Data

Formula

C19H12N2O2Cl2
Molecular Weight 371.22 CAS No. 280744-09-4
Solubility (25°C)* In vitro DMSO 23 mg/mL (61.95 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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.
Targets
GSK-3α [1]
(Cell-free assay)		 GSK-3β [1]
(Cell-free assay)
34.3 nM ~34.3 nM
In vitro SB 216763 displays similar potency for GSK-3β with 96% inhibition at 10 μM while exhibiting minimal activity against 24 other protein kinases including PKBα and PDK1 with IC50 of >10 μM. SB 216763 stimulates glycogen synthesis in human liver cells with EC50 of 3.6 μM, and induces dose-dependent transcription of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells with a maximum 2.5-fold induction at 5 μM. [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 μM in contrast with the effect of lithium chloride at which 10 mM is required. SB 216763 at 3 μM also completely prevents death of chicken dorsal root ganglion sensory neurones induced by LY-294002 regardless of NGF. SB 216763 treatment at 5 μM 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 β-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 μM 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-3β, 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-α 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]

Protocol (from reference)

Kinase Assay:[1]
  • 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-3α, 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, and 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. The total ATP concentration is 10 μM. 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.
Cell Assay:[3]
  • Cell lines

    BXPC-3, MIA-PaCa2, PANC1, ASPC1, and CFPAC cells

  • Concentrations

    Dissolved in DMSO, final concentrations ~50 μM

  • Incubation Time

    24, 48, and 72 hours

  • 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.
Animal Study:[4]
  • Animal Models

    C57BL/6N mice with lung inflammation and fibrosis induced by bleomycin (BLM)

  • Dosages

    20 mg/kg

  • Administration

    Intravenously

Customer Product Validation

Data from [Mol Cancer Ther, 2014, 13(1), 37-48]

Data from [Data independently produced by , , Cancer Res, 2018, doi:10.1158/0008-5472]

Data from [Data independently produced by , , Mol Cancer Ther, 2013, 13(2): 454-67 ]

Data from [Data independently produced by , , Am J Transl Res, 2016, 8(5):1985-97.]

Selleck's SB216763 has been cited by 93 publications

The ribosomal protein S6 kinase alpha-1 (RPS6KA1) induces resistance to venetoclax/azacitidine in acute myeloid leukemia [ Leukemia, 2023, 37(8):1611-1625] PubMed: 37414921
The ribosomal protein S6 kinase alpha-1 (RPS6KA1) induces resistance to venetoclax/azacitidine in acute myeloid leukemia [ Leukemia, 2023, 37(8):1611-1625] PubMed: 37414921
Kidins220 sets the threshold for survival of neural stem cells and progenitors to sustain adult neurogenesis [ Cell Death Dis, 2023, 14(8):500] PubMed: 37542079
The GSK3β/Mcl-1 axis is regulated by both FLT3-ITD and Axl and determines the apoptosis induction abilities of FLT3-ITD inhibitors [ Cell Death Discov, 2023, 9(1):44] PubMed: 36739272
Progranulin Protects against Hyperglycemia-Induced Neuronal Dysfunction through GSK3β Signaling [ Cells, 2023, 12(13)1803] PubMed: 37443837
Minichromosome maintenance 6 protects against renal fibrogenesis by regulating DUSP6-mediated ERK/GSK-3β/Snail1 signaling [ iScience, 2023, 26(10):107940] PubMed: 37810227
Dexmedetomidine Ameliorates Cardiac Ischemia/Reperfusion Injury by Enhancing Autophagy Through Activation of the AMPK/SIRT3 Pathway [ Drug Des Devel Ther, 2023, 17:3205-3218] PubMed: 37908314
ULK1-mediated metabolic reprogramming regulates Vps34 lipid kinase activity by its lactylation [ Sci Adv, 2023, 9(22):eadg4993] PubMed: 37267363
ULK1-mediated metabolic reprogramming regulates Vps34 lipid kinase activity by its lactylation [ Sci Adv, 2023, 9(22):eadg4993] PubMed: 37267363
Skp2 stabilizes Mcl-1 and confers radioresistance in colorectal cancer [ Cell Death Dis, 2022, 13(3):249] PubMed: 35301297

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.