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| 10mg |
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| 25mg |
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| 250mg |
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Purity: ≥98%
SB415286 is a novel, potent, selective, cell permeable and ATP-competitive GSK3α (glycogen synthase kinase-3alpha) inhibitor with potential anti-inflammatory activity. It has an equal inhibitory effect on GSK3α and an IC50/Ki of 78 nM/31 nM. In human liver cells, SB-415286 reduced GSK-3β activity, increased glycogen synthesis, and induced the expression of a reporter gene controlled by catenin-LEF/TCF in HEK293 cells. It can stop the cell death brought on by suppressed PI3k pathway activity in primary neurons. Additional research revealed that SB-415286's decreased GSK3β activity could prevent the rapamycin-mediated down-regulation of cyclin D1, cell cycle arrest, and chemosensitivity. A multifunctional serine/threonine kinase called glycogen synthase kinase-3 (GSK-3) is crucial for the necrosis and apoptosis of cardiomyocytes.
| Targets |
hGSK-3α (IC50 = 77.5 nM); hGSK-3β (IC50 = 77.5 nM)
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|---|---|
| ln 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. In HEK293 cells, SB-415286 activates the transcription of a reporter gene controlled by the β-catenin-LEF/TCF pathway[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].
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| ln Vivo |
SB 415286 (10 mg/kg twice daily) administration decreases the intensity and severity of the rat colonic inflammation caused by trinitrobenzene sulphonic acid (TNBS), as well as the loss of body weight, which is linked to the downregulation of NF-B activity, which is involved in the production of proinflammatory mediators. In vivo growth of Neuro-2A cells in nude mice is markedly slowed down by SB 415286 treatment at 1 mg/kg.
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| Enzyme 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 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 (IC50 determinations) or 2.7 μCi [33P]γ-ATP (Ki determinations). starts the assay. The total ATP concentration is 10 μM (based on IC50 calculations) or 0 to 45 μM (based on Ki calculations). After 30 minutes of room temperature incubation, the assay is terminated by adding a third of the assay volume of 2.5% (v/v) H3PO4 containing 21 mM ATP. After being spotted onto P30 phosphocellulose mats, samples are washed six times in 0.5% (v/v) H3PO4 before being analyzed. In sample bags containing Wallac betaplate scintillation fluid, the filter mats are sealed. By counting the mats in a Wallac microbeta scintillation counter, one can determine the amount of 33P incorporated into the substrate peptide[1].
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| Cell Assay |
B65 cells are used after 24 h of in vitro culture. CGN are used 7-8 days after in vitro creation. One hour before adding H2O2, lithium and SB-415286 are added to the neuronal preparation at the exact concentrations (50 M to 1 mM) after being dissolved in culture media and DMSO, respectively. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium] method is used to measure the loss in cell viability. MTT is added to the cells at a final concentration of 250 M, and after 1 hour of incubation, a dark blue formazan product is produced as a result of MTT's reduction. Following the removal of the media, the cells are dissolved in dimethylsulfoxide. Utilizing a microplate reader, the amount of formazan produced is determined by the change in absorbency at 595 nm. Results are presented as percentages of viability. The absorbency measured from non-treated cells is taken to be 100%[2].
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| Animal Protocol |
Male Wistar rats with acute colitis provoked by trinitrobenzene sulphonic acid (TNBS)
~1 mg/kg Administered subcutaneously twice daily |
| References |
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| Additional Infomation |
SB 415286 is a member of the class of maleimides carrying 3-chloro-4-hydroxyphenylamino and 2-nitrophenyl substituents at positions 3 and 4 respectively. It has a role as an EC 2.7.11.26 (tau-protein kinase) inhibitor, an antioxidant, a neuroprotective agent and an apoptosis inducer. It is a member of maleimides, a member of phenols, a member of monochlorobenzenes, a substituted aniline, a secondary amino compound and a C-nitro compound.
3-(3-chloro-4-hydroxyphenylamino)-4-(4-nitrophenyl)-1H-pyrrole-2,5-dione has been reported in Penicillium with data available. |
| Molecular Formula |
C16H10CLN3O5
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|---|---|
| Molecular Weight |
359.7207
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| Exact Mass |
359.03
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| Elemental Analysis |
C, 53.42; H, 2.80; Cl, 9.85; N, 11.68; O, 22.24
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| CAS # |
264218-23-7
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| Related CAS # |
264218-23-7
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| PubChem CID |
4210951
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
595.8±50.0 °C at 760 mmHg
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| Flash Point |
314.1±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.746
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| LogP |
2.06
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
617
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C(C([H])=C([H])C(=C1[H])N([H])C1C(N([H])C(C=1C1=C([H])C([H])=C([H])C([H])=C1[N+](=O)[O-])=O)=O)O[H]
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| InChi Key |
PQCXVIPXISBFPN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H10ClN3O5/c17-10-7-8(5-6-12(10)21)18-14-13(15(22)19-16(14)23)9-3-1-2-4-11(9)20(24)25/h1-7,21H,(H2,18,19,22,23)
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| Chemical Name |
3-(3-chloro-4-hydroxyanilino)-4-(2-nitrophenyl)pyrrole-2,5-dione
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| Synonyms |
SB-415286; SB415286; SB 415286
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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: 72~100 mg/mL (200.2~278 mM)
Ethanol: ~72 mg/mL (~200.2 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.95 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 (6.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7799 mL | 13.8997 mL | 27.7994 mL | |
| 5 mM | 0.5560 mL | 2.7799 mL | 5.5599 mL | |
| 10 mM | 0.2780 mL | 1.3900 mL | 2.7799 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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