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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 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.
| Targets |
GSK-3α (IC50 = 34.3 nM); GSK-3β (IC50 = 34.3 nM)
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| 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].
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| 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
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| 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.
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| 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.
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| 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).
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| References |
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| Additional Infomation |
3-(2,4-dichlorophenyl)-4-(1-methyl-3-indolyl)pyrrole-2,5-dione is a member of indoles and a member of maleimides.
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| Molecular Formula |
C19H12CL2N2O2
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|---|---|
| Molecular Weight |
371.2168
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| Exact Mass |
370.027
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| Elemental Analysis |
C, 61.47; H, 3.26; Cl, 19.10; N, 7.55; O, 8.62
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| CAS # |
280744-09-4
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| Related CAS # |
280744-09-4
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| PubChem CID |
176158
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| Appearance |
Orange to red solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
598.1±50.0 °C at 760 mmHg
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| Melting Point |
287-288.6ºC(lit.)
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| Flash Point |
315.5±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.702
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| LogP |
4.79
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
621
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C([H])=C(C([H])=C([H])C=1C1C(N([H])C(C=1C1=C([H])N(C([H])([H])[H])C2=C([H])C([H])=C([H])C([H])=C12)=O)=O)Cl
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| InChi Key |
JCSGFHVFHSKIJH-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
3-(2,4-dichlorophenyl)-4-(1-methylindol-3-yl)pyrrole-2,5-dione
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| Synonyms |
SB216763; SB-216763; 3-(2,4-Dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione; SB-216763; SB216763; 3-(2,4-dichlorophenyl)-4-(1-methylindol-3-yl)pyrrole-2,5-dione; 1H-Pyrrole-2,5-dione, 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-; MFCD09753369; SB 216763
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: ~23 mg/mL (~62.0 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.73 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 1% DMSO+30% polyethylene glycol+1% Tween 80: 11mg/mL |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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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 |
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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