受注:045-509-1970 |
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Synonyms | PNU-151774E,FCE28073 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C17H19FN2O2.CH4O3S |
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分子量 | 398.45 | CAS No. | 202825-46-5 | ||||
Solubility (25°C)* | 体外 | DMSO | 80 mg/mL (200.77 mM) | ||||
Water | 80 mg/mL (200.77 mM) | ||||||
Ethanol | 13 mg/mL (32.62 mM) | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | Safinamide Mesylate (PNU-151774E, FCE28073) is mesylate salt of Safinamide, selectively and reversibly inhibits MAO-B with IC50 of 98 nM, exhibits 5918-fold selectivity against MAO-A. Phase 3. |
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in vitro | Safinamide is a highly selective MAO-B inhibitor in rat brain mitochondria, with an IC50 of 98 nM. safinamide inhibits MAO-B in human brain with an IC50 of 9 nM. Safinamide has high affinity for the Na+ channel-binding site II in rat cortical membranes, with an IC50 of 8 μM. Safinamide inhibits the fast Na+ currents in a concentration- and state-dependent manner in rat cortical neurons. Safinamide blocks N-Type Ca2+ currents in rat cortical neurons with IC50 of 23 μM. Safinamide inhibits glutamate release induced by depolarizing conditions in rat hippocampal synaptosomes with IC50 of 9 μM. Safinamide incubated 1 hour before veratridine reduces the neuron damage with an IC50 1.4 μM through blockade of opening voltage-dependent Na+ and Ca2+ channels in rat primary cortical neurons. [1] Safinamide binds to human MAO B with a Ki of 0.5 μM. Safinamide binds to human MAO B in an extended conformation occupying both flavin and entrance cavity. [2] |
in vivo | Safinamide orally administrated dose-dependently inhibits mouse brain MAO-B with IC50 of 0.6 mg/kg, and MAO-B activity recovers quickly, starting from 8 hours. Safinamide significantly inhibits cell body degeneration in the substantia nigra pars compacta. Safinamide intraperitoneally administered 15 minutes before kainic acid protects against hippocampal neuron loss, starting at 10 mg/kg showing neuroprotective properties. Safinamide intraperitoneally administrated at dose of 100 mg/kg shows a relevant neurorescuing effect on hippocampal neurons when given 3 hours after ischemia. Safinamide has a high oral bioavailability (80-92%), is rapidly absorbed in plasma after reaching the peak within 0.5-2 hours declines, with a terminal half-life of about 3, 7, and 13 hours in mice, rats, and monkeys, respectively. [1] |
特徴 | Greater than 5,000-fold potency in inhibiting MAO-B vs. MAO-A. |
キナーゼアッセイ | Enzyme Activity Assay | |
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The enzyme activities are assessed with a radioenzymatic assay using the selective substrates 14C-phenylethylamine (PEA) for MAO-B. The mitochondrial pellet (500 μg protein) is resuspended in 200 μL of 0.1 M phosphate buffer, pH 7.40, and is added to 50 μL of the solution of safinamide or of buffer and incubated for 30 min at 37 °C (preincubation). Then the substrate in 50 μL of 0.5 μM 14CPEA is added and the assay mixture is incubated at 37 °C for 10 min. The reaction is stopped by adding 0.2 mL of perchloric acid. After centrifugation, the acidic radioactive metabolites are extracted with 3 mL of toluene and the radioactivity of the organic phase is measured by liquid scintillation spectrometry at 90% efficiency. The enzymatic activity is expressed as nanomoles of substrate transformed per milligram of protein per minute (nmol mg-1 min-1). Safinamide inhibition curves are obtained from five to eight different concentrations (10-10-10-5 M), each in duplicate, and the IC50 is determined using nonlinear regression analysis. | ||
動物実験 | 動物モデル | DA-depleted C57BL mice |
投薬量 | 20 mg/kg | |
投与方法 | Inject intraperitoneally in a single dose |
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長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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