Item no. |
S1472-10 |
Manufacturer |
Selleckchem
|
CASRN |
202825-46-5 |
Amount |
10 mg |
Category |
|
Type |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
PNU-151774E,FCE28073, MAO-B;MAO |
Similar products |
Safinamide |
Available |
|
Administration |
Inject intraperitoneally in a single dose |
Animal Models |
DA-depleted C57BL mice |
Chemical Name |
(S)-2-(4-(3-fluorobenzyloxy)benzylamino)propanamide, methanesulfonate |
Clinical Trials |
Safinamide is currently in a Phase II clinical trial in Parkinson's Disease. |
Description |
Safinamide Mesylate is mesylate salt of Safinamide, which selectively and reversibly inhibits MAO-B with IC50 of 0.45 uM. |
Dosages |
20 mg/kg |
Features |
5000-fold more potent in inhibiting MAO-B versus MAO-A |
Formulation |
sterile 0.9% sodium chloride solution |
IC50 |
0.45 uM [3], 0.45 uM [3], 0.45 uM [3], 0.45 uM [3], 0.45 uM [3], 0.45 uM [3] |
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 uM. 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 23 uM. Safinamide inhibits glutamate release induced by depolarizing conditions in rat hippocampal synaptosomes with IC50 of 9 uM. Safinamide incubated 1 hour before veratridine reduces the neuron damage with an IC50 1.4 uM 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 uM. 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] |
Kinase Assay |
[3], Enzyme Activity Assay, The enzyme activities are assessed with a radioenzymatic assay using the selective substrates 14C-phenylethylamine (PEA) for MAO-B. The mitochondrial pellet (500 ug protein) is resuspended in 200 uL of 0.1 M phosphate buffer, pH 7.40, and is added to 50 uL of the solution of safinamide or of buffer and incubated for 30 min at 37 C (preincubation). Then the substrate in 50 uL of 0.5 uM 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. |
Molecular Weight (MW) |
398, 45 |
Picture ChemicalStructure Description |
Safinamide Mesylate (FCE28073) Chemical Structure |
Solubility (25C) |
DMSO 80 mg/mL, Water 80 mg/mL, Ethanol 13 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.
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