SB216763

Alias: SB216763; SB-216763; SB 216763
Cat No.:V0212 Purity: ≥98%
SB216763 is a novel, potent and selective GSK-3 (glycogen synthase kinase-3) inhibitor with anti-inflammatory activiity and neuro-protective effects as it canpromote DNA repair in ischemic retinal neurons.
SB216763 Chemical Structure CAS No.: 280744-09-4
Product category: GSK-3
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

SB216763 is a novel, potent and selective GSK-3 (glycogen synthase kinase-3) inhibitor with anti- inflammatory activiity and neuro-protective effects as it can promote DNA repair in ischemic retinal neurons. It has an IC50 of 34.3 nM for GSK-3β and an IC50 of 34.3 nM for GSK-3α. A multifunctional serine/threonine kinase called glycogen synthase kinase-3β (GSK-3β) is crucial for the necrosis and apoptosis of cardiomyocytes. When grown on mouse embryonic fibroblasts (MEFs), SB-216763, a glycogen synthase kinase-3 (GSK3) inhibitor, can keep mouse embryonic stem cells (mESCs) in a pluripotent state in the absence of exogenous leukemia inhibitory factor (LIF). Ex vivo PI3K pathway-mediated cell death can be prevented in neurones of the central and peripheral nervous systems by SB-216763 treatment.

Biological Activity I Assay Protocols (From Reference)
Targets
GSK-3α (IC50 = 34.3 nM); GSK-3β (IC50 = 34.3 nM)
ln Vitro
In HEK293 cells, SB-216763 (10–20 μM.) induces -catenin-mediated transcription in a dose-dependent manner. In long-term culture, SB-216763 (10, 15 and 20 μM) can keep mESCs with a pluripotent-like morphology. For more than a month, SB-216763 (10 μM) can keep J1 mESCs in a pluripotent state[2]. SB-216763 has an IC50 of 34 nM, which inhibits GSK-3[3]. Both human GSK-3α and GSK-3β are effectively inhibited by SB-216763[5].
ln Vivo
SB216763 (20 mg/kg, i.v.) significantly improves the survival of BLM-treated mice. Compared to BLM-treated mice, mice that were randomly assigned to receive BLM plus SB216763 exhibit a notable reduction. The severity of alveolitis caused by BLM is lessened by SB216763 (20 mg/kg, intravenously)[1]. When the rabbits' hearts are subjected to 30-min CAO, the infarct size is significantly reduced by SB 216763 (0.2 mg/kg, i.v.) with either 17β-E100 or Geni100[4
Enzyme 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 glycogen synthase region that the GS-2 peptide sequence corresponds to is one that GSK-3 phosphorylates. The addition of 0..34 μCi [33P]γ-ATP starts the assay. The total ATP concentration is 10 μM. After 30 minutes of incubation at room temperature, the assay is terminated by adding a third of the assay volume of 2.5% (v/v) H3PO4 containing 21 mM ATP. Samples are spotted onto P30 phosphocellulose mats and six times washed in 0.5% (v/v) H3PO4. Filter mats are placed inside sample bags containing Wallac betaplate scintillation fluid and sealed. By counting the mats in a Wallac microbeta scintillation counter, 33P incorporation into the substrate peptide is identified.
Cell Assay
MESCs maintained with LIF or 10 µM SB-216763 for more than a month are resuspended at 40,000 cells/mL in LIF-free mESC medium. The hanging drop method is used to prepare EBs. A 10-cm Petri dish lid is lined with 20 µL -L drops of mESCs. The lids are put on Petri dishes with 10 mL of HBSS, and the EBs are then allowed to form and grow for 4 days in the incubator. In a 24-well plate, 15-20 EBs are transferred to a well containing LIF-free mESC medium after 4 days. Every two days, the medium is changed, and aggregates of independently beating cells are counted and observed.
Animal Protocol
Four groups of mice (n=12/group) are formed as follows: Intrathecal saline plus vehicle (25 percent dimethyl sulfoxide, 25 percent polyethylene glycol, and 50 percent saline), intrathecal saline plus SB216763 (20 mg/kg) dissolved in vehicle, intrathecal BLM (3 U/kg) plus vehicle, and intrathecal BLM plus SB216763 (20 mg/kg) in vehicle are the four options. In another set of tests, mice (n=12/group) were given intratracheal saline + vehicle, intratracheal BLM, or intratracheal BLM + SB216763 to see how their cytokine expression was affected. BLM is injected intratracheally into mice (n=15/group) on day 0 to cause pulmonary fibrosis. SB216763 dissolved in vehicle or vehicle alone is given intravenously to BLM and saline-treated mice at day 0 and then twice weekly intraperitoneally until day 28. On days 2, 7, and 28, mice are killed by inhaling CO2. The cohorts of mice used in the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) experiments are as follows: saline-treated mice (n = 6), BLM-treated mice (n = 6), and BLM + SB216763-treated mice (n = 6).
References

[1]. 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (SB216763), a glycogen synthase kinase-3 inhibitor, displays therapeutic properties in a mouse model of pulmonary inflammation and fibrosis. J.Pharmacol.Exp.Ther.2010

[2]. Glycogen synthase kinase 3 (GSK3) inhibitor, SB-216763, promotes pluripotency in mouse embryonic stem cells.PLoS One. 2012;7(6):e39329. Epub 2012 Jun 26.

[3]. The first synthesis of [(11)C]SB-216763, a new potential PET agent for imaging of glycogen synthase kinase-3 (GSK-3).Bioorg Med Chem Lett. 2011 Jan 1;21(1):245-9. Epub 2010 Nov 11.

[4]. The ceiling effect of pharmacological postconditioning with the phytoestrogen genistein is reversed by the GSK3beta inhibitor SB 216763 [3-(2,4-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione] through mitochondrial ATP-dependent potassium channel opening.

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

[6]. Inhibition of glycogen synthase kinase 3beta ameliorates triptolide-induced acute cardiac injury by desensitizing mitochondrial permeability transition. Toxicol Appl Pharmacol. 2016 Dec 15;313:195-203.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C19H12CL2N2O2
Molecular Weight
371.2168
Exact Mass
370.02758
Elemental Analysis
C, 61.47; H, 3.26; Cl, 19.10; N, 7.55; O, 8.62
CAS #
280744-09-4
Appearance
Solid powder
SMILES
CN1C=C(C2=CC=CC=C21)C3=C(C(=O)NC3=O)C4=C(C=C(C=C4)Cl)Cl
InChi Key
JCSGFHVFHSKIJH-UHFFFAOYSA-N
InChi Code
InChI=1S/C19H12Cl2N2O2/c1-23-9-13(11-4-2-3-5-15(11)23)17-16(18(24)22-19(17)25)12-7-6-10(20)8-14(12)21/h2-9H,1H3,(H,22,24,25)
Chemical Name
3-(2,4-dichlorophenyl)-4-(1-methylindol-3-yl)pyrrole-2,5-dione
Synonyms
SB216763; SB-216763; SB 216763
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~23 mg/mL (~62.0 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 11mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.6938 mL 13.4691 mL 26.9382 mL
5 mM 0.5388 mL 2.6938 mL 5.3876 mL
10 mM 0.2694 mL 1.3469 mL 2.6938 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Biological Data
  • SB216763

  • SB216763

    SB216763 reduced the magnitude of BLM-induced alveolitis. Mice were treated with saline, BLM + vehicle, or BLM + SB216763 (20 mg/kg; n = 12/group) as described under Materials and Methods. J Pharmacol Exp Ther. 2010 Mar;332(3):785-94

  • SB216763

    Histologic examination of the lungs in BLM-induced pulmonary fibrosis. On day 28, mice treated with BLM + vehicle, BLM + SB216763, or saline were sacrificed, and histologic examination was performed by H&E staining (A–F) and Masson''''s trichrome staining (G–I); J Pharmacol Exp Ther. 2010 Mar;332(3):785-94

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