SB 415286 is a potent and selective cell-permeable, ATP-competitive GSK3α inhibitor with an IC50 and a Ki of 78 and 31 nM, respectively. SB 415286 competes with ATP. SB 415286 has minimal activity against 24 other protein kinases (IC50 > 10 μ M). SB 415286 stimulates glycogen synthesis, gene transcription and is neuroprotective. As a result of GSK3 inhibition, SB 415286 stimulates glycogen synthesis in the Chang human liver cell line with an EC50 value of 2.9 µM. SB 415286 also protects primary neurons from death induced by the PI3-kinase pathway. In L6 myotubes, SB 415286 induced a much greater activation of GS (6.8-fold) . In adipocytes, SB 415286 caused a comparable activation of GS despite a substantial differentiation-linked reduction in GSK3 expression ( approximately 85%) indicating that GSK3 remains an important determinant of GS activation in fat cells. SB 415286 induced expression of a beta-catenin-LEF/TCF regulated reporter gene in HEK293 cells.
|Cell lines||OPM-2, RPMI-8226, U-266, and INA-6|
|Preparation method||Exposing cells to different concentrations of SB 415286 for 48 or 72 hours in 96-flat well plates. 48 or 72 hours later, [3H]thymidine is added to the cultures (10 μCi/well) for the last 12 hours. Using a top count β-counter to evaluate the [3H]thymidine incorporation by scintillation counting .Assessing apoptosis by annexin V/Propidium Iodide staining or by detection of mitochondrial membrane potential. Evaluating cell death by the analysis of Forward/Side scatter fluorescence changes. Fluorescence Activated Cell Sorting (FACS) analysis is performed .|
|Concentrations||Dissolved in DMSO, final concentrations ~10 μM|
|Incubation time||48, or 72 hours|
|Animal models||Male Wistar rats with acute colitis provoked by trinitrobenzene sulphonic acid (TNBS)|
|Formulation||Dissolved in DMSO|
|Dosages||~1 mg/kg mg/kg|
|Administration||Administered subcutaneously twice daily|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 70 mg/mL|
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