| CAS NO: | 333745-53-2 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
| Molecular Weight (MW) | 474.07 |
|---|---|
| Formula | C22H19ClN2O6S |
| CAS No. | 333745-53-2 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: ≥ 150 mg/mL |
| Water: <1 mg/mL | |
| Ethanol: <1 mg/mL | |
| Solubility (In vivo) | C1=C(NC(CN(C2=CC(Cl)=CC=C2OC)S(C2=CC=CC=C2)(=O)=O)=O)C=C2OCOC2=C1 |
| Synonyms | LX-2343; LX 2343; LX2343 |
| In Vitro | In vitro activity: Intracellular ROS assay, the production of intracellular ROS was measured by fluorescence microscopy (Olympus Company, Tokyo, Japan) using an oxidation-sensitive probe, 20,70-dichlorofluorescein diacetate (DCFH-DA) (Beyotime Company, Haimen, China). After exposing either the SH-SY5Y or the primary neuronal cells to STZ (0.8 mmol/L or 0.4 mmol/L, respectively) with different concentrations of LX2343 (5, 10, or 20 μmol/L) for 8 h, the ROS level was measured according to the manufacturer's protocol. Kinase Assay: GSK-3β enzymatic activity assay, GSK-3β inhibition by LX2343 was evaluated by performing an ELISA according to the published approach. Briefly, recombinant human GSK-3β (Invitrogen, Grand Island, NY, USA) was added to the reactions with the substrate-recombinant human TAU-441 (Merck Millipore, Darmstadt, Germany) in a 5:1 ratio. The reaction buffer contained 40 mmol/L HEPES, 5 mmol/L MgCl2, 1 mmol/L EDTA, 50 mg/mL of heparin and 100, 30, or 10 μmol/L ATP, and had a pH of 7.2. The reaction mixture was incubated at 37 °C for 1 h. The amount of phosphorylated TAU-441 was measured using a human Tau [pS396] ELISA kit (Invitrogen, Grand Island, NY, USA). Cell Assay: The viability of the cultured cells was determined by assaying the reduction of MTT to formazan. SH-SY5Y or neuronal cells were seeded overnight in 48-well plates at a density of 105 cells/well in 100 μL medium. The cells were then incubated with different concentrations of LX2343 (5, 10, or 20 μmol/L) and STZ (0.8 mmol/L for SH-SY5Y cells, 0.4 mmol/L for neuronal cells) for 24 h and washed twice with PBS, followed by the addition of MTT (0.5 mg/mL). After incubation at 37 °C for 4 h, 200 μL DMSO was added to dissolve the formazan crystals, and the absorbance at 490 nm was measured using an M5 spectrophotometer (Molecular Devices, Sunnyvale, CA, USA). |
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| In Vivo | Forty adult male Sprague Dawley (SD) rats weighing 140–160 g were used in the study. The rats were randomly divided into four groups (ten in each group) and maintained under standard conditions at room temperature (22 °C) with a 12 h light/dark cycle. The animals were purchased from Slac Laboratory Animal Co Ltd (Shanghai, China). The rats in the first group (V) treated with vehicle did not have surgery because previous studies and our results (Supplementary Figure S1A-S1B) both demonstrated that there was no significant difference in the behavior and cognitive function of control rats (without surgery) and that of sham rats (recipients of an ICV injection of vehicle). The rats in the second group (SV) were injected with ICV-STZ (3 mg/kg bilaterally) and vehicle, and the rats in the third (SL) and fourth (SH) groups were injected with ICV-STZ and different doses of LX2343 (7 and 21 mg/kg, respectively). LX2343 was dissolved in 3% DMSO and 5% Tween-80. Before surgery, pre-administration of LX2343 was carried out for 2 weeks. The treatment was maintained for 21 consecutive days after surgery. The brief surgical procedure was performed as follows. Rats were anesthetized with 10% chloral hydrate intraperitoneally and placed on a stereotaxic frame. Holes were drilled in the skull on both sides over the lateral ventricles according to the following coordinates: 0.8 mm posterior to the bregma, 1.5 mm lateral to the saggital suture, and 3.6 mm beneath the surface of the brain. The lesion groups received a bilateral ICV injection of STZ (3 mg/kg, 10 μL/each side). STZ was dissolved in artificial CSF (147 mmol/L NaCl, 2.9 mmol/L KCl, 1.6 mmol/L MgCl2, 1.7 mmol/L CaCl2, and 2.2 mmol/L dextrose). All microinjections were performed slowly at a speed of 2 μL/min, and the needle remained in position for more than 2 min to prevent reflux along the injection tract. |
| Animal model | Male Sprague Dawley (SD) rats |
| Formulation & Dosage | 7 and 21 mg/kg; 3% DMSO and 5% Tween-80; IV injection |
| References | Acta Pharmacol Sin. 2017 Aug;38(8):1104-1119. |
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