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| 25mg |
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| Targets |
Mofegiline HCl targets monoamine oxidase B (MAO-B), an enzyme responsible for the oxidative deamination of monoamine neurotransmitters. The compound is a potent and irreversible inhibitor of MAO-B, with an IC₅₀ of 3.6 nM for the rat brain mitochondrial enzyme. It exhibits selectivity for MAO-B over MAO-A (IC₅₀ = 680 nM). Additionally, Mofegiline inhibits vascular adhesion protein-1 (VAP-1/SSAO), an enzyme involved in leukocyte adhesion and transmigration, with an IC₅₀ of 20 nM for the human enzyme. The compound's primary target is MAOB (gene).
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| ln Vitro |
Rat brain mitochondrial MAO is inhibited by murfegiline hydrochloride (MDL72974A) in a concentration- and time-dependent manner[1]. In the rat striatum, murfegiline hydrochloride (MDL72974A) has a poor effect[2] but reduces [3H]GBR-12935 (1 nM) binding (IC50 >100 μM) and [3H]dopamine (15 nM) uptake (IC50 of 31.8 μM). The aortas of dogs, rats, cows, and humans are all susceptible to SSAO inhibition by murfegiline hydrochloride (MDL72974A), with IC50 values of 2 nM, 5 nM, 80 nM, and 20 nM, respectively [3].
In vitro, Mofegiline potently inhibits MAO-B activity in rat brain mitochondrial preparations, demonstrating an IC₅₀ of 3.6 nM. It is selective for MAO-B over MAO-A, with an approximately 189-fold difference in potency. Mofegiline also inhibits human SSAO/VAP-1 with an IC₅₀ of 20 nM. The compound's irreversible inhibition of MAO-B leads to increased levels of monoamine neurotransmitters in the brain. Its in vitro activity has been well-characterized in enzyme inhibition assays using mitochondrial preparations. |
| ln Vivo |
Murfegiline hydrochloride (MDL72974A) has the capacity to block MPTP in a mouse neurotoxicity model and inhibit MAO-B activity in vitro in a rat model (1.25 mg/kg; i.p.; 18 hours prior to MPTP treatment) [1].
In vivo, Mofegiline has been shown to reduce MPTP-induced decreases in striatal levels of dopamine, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in mice when administered at a dose of 1.25 mg/kg. This protective effect is attributed to its inhibition of MAO-B, which prevents the conversion of MPTP to its neurotoxic metabolite. The compound was studied for its potential effects against Parkinson's disease and Alzheimer's disease. Mofegiline's ability to cross the blood-brain barrier and inhibit brain MAO-B makes it a valuable tool for studying neuroprotective strategies. |
| Enzyme Assay |
In vitro enzyme assays for Mofegiline typically involve measuring the inhibition of MAO-B activity using mitochondrial preparations. A typical protocol: rat brain mitochondria are isolated and incubated with varying concentrations of Mofegiline (0.1 nM to 10 μM) in assay buffer. The reaction is initiated by the addition of a substrate such as kynuramine or benzylamine, and the production of the oxidative deamination product is monitored spectrophotometrically. IC₅₀ values are calculated from inhibition curves. For SSAO/VAP-1 inhibition assays, recombinant human SSAO is used with a fluorogenic substrate, and fluorescence is measured over time. Each concentration is tested in triplicate, and experiments are repeated at least three times. Positive controls include deprenyl (for MAO-B) or other known MAO inhibitors.
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| Cell Assay |
In vitro cell-based assays for Mofegiline are performed using neuronal cell lines or primary neuronal cultures to assess neuroprotective effects. A typical protocol: cells are pre-treated with Mofegiline at concentrations ranging from 0.1 to 10 μM for 1-2 hours, then exposed to a neurotoxic insult such as MPTP or MPP⁺. Cell viability is assessed using MTT or LDH release assays. MAO-B activity in cell lysates is measured by fluorometric or colorimetric assays. Neurotransmitter levels in cell culture supernatants can be measured by HPLC. Each condition is tested in triplicate, and experiments are repeated at least three times. Positive controls include deprenyl or other MAO-B inhibitors.
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| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (150-400 g)[1]
Doses: Group 1: 0.1-2.5 mg/kg; Group 2: 0.05-5 mg/kg Route of Administration: po (oral gavage); single dose for group 1, as for group 2, one time/day for 14 days Experimental Results:demonstrated the inhibition effect on rat brain MAO-A and MAO-B with EC50s of 8 mg/kg and 0.18 mg/kg, respectively, in group 1. Resulted more potent efficacy on MAO-A inhibition in a daily dosed-manner (group 2) than single dose (group 1) manner, indicating a long half-life of Mofegiline hydrochloride. Animal/Disease Models: Mate SwissWebster (CF-W) mice (25-30 g)[1] Doses: 1.25 mg/kg Route of Administration: intraperitoneal (ip) injection; 18 hrs (hrs (hours)) prior to administration of MPTP (20 mg/kg; i.p.; 4 times for two-hourly intervals, for 8 days) Experimental Results:Rescued MPTP-induced decreases in striatal levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in mice. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (150-400 g) injected with Tyramine (HY-W007606) (1.25-80 μg/kg; i.v.)[1] Doses: Group 1: 1.8, 9 mg/kg; Group 2: 0.1, 1 mg/kg Route of Administration: po (oral gavage); single dose for group 1, as for group 2, one time/day for 14 days Experimental Results:Did not Dramatically potentiate the cardiovascular effects of intraduodenally administered Tyramine (HY-W007606) in anaesthetised rats. In vivo animal studies for Mofegiline are conducted in mouse models of MPTP-induced neurotoxicity. A typical protocol: male C57BL/6 mice are administered Mofegiline via intraperitoneal injection at doses of 0.5-5 mg/kg, 30-60 minutes before MPTP administration (20-30 mg/kg, IP). After 7-14 days, mice are euthanized, and striatal tissues are dissected for neurotransmitter analysis by HPLC-ECD. Tyrosine hydroxylase immunohistochemistry is performed to assess dopaminergic neuron survival. Behavioral tests such as the rotarod test or open field test may be conducted to assess motor function. Efficacy is assessed by comparing dopamine levels and neuronal survival between treatment and vehicle control groups. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Mofegiline HCl have been partially characterized. The compound is soluble in water (up to 30 mg/ml). As an irreversible MAO-B inhibitor, its pharmacodynamic effects outlast its presence in plasma. The compound is administered orally or intraperitoneally in preclinical studies. Its ability to cross the blood-brain barrier is demonstrated by its in vivo neuroprotective effects. Specific pharmacokinetic parameters such as half-life, volume of distribution, and clearance are not widely reported in the literature. The compound should be stored at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
Toxicological data for Mofegiline HCl are limited to observations from preclinical studies. At therapeutic doses in animal models, the compound is generally well-tolerated. As a MAO-B inhibitor, it may have potential for drug-drug interactions with serotonergic agents. The compound has not undergone formal toxicology testing for regulatory purposes. Standard laboratory safety precautions should be followed when handling Mofegiline HCl: use of personal protective equipment (gloves, safety goggles, lab coat) and handling in a well-ventilated fume hood. The compound should be stored at -20°C for long-term stability. Researchers should consult the safety data sheet (SDS) before handling.
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| References |
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| Additional Infomation |
Additional information for Mofegiline HCl: The compound has a CAS number of 120635-25-8. Its molecular formula is C₁₁H₁₃F₂N·HCl and molecular weight is 233.68 g/mol. The IUPAC name is (2E)-2-(fluoromethylidene)-4-(4-fluorophenyl)butan-1-amine; hydrochloride. Synonyms include MDL 72974A. Purity is typically ≥95%. The compound is an irreversible inhibitor of MAO-B and SSAO/VAP-1. It was studied for Parkinson's disease and Alzheimer's disease. It is for research use only and is not approved for clinical applications. No FDA approvals exist.
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| Molecular Formula |
C11H14CLF2N
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| Molecular Weight |
233.6868
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| Exact Mass |
233.078
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| CAS # |
120635-25-8
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| PubChem CID |
6446650
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| Appearance |
White to off-white solid powder
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| Boiling Point |
322.7ºC at 760 mmHg
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| Flash Point |
149ºC
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| Vapour Pressure |
0.00232mmHg at 25°C
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| LogP |
4.072
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
15
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| Complexity |
184
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC=C1CC/C(=C\F)/CN)F.Cl
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| InChi Key |
QUCNNQHLIHGBIA-HCUGZAAXSA-N
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| InChi Code |
InChI=1S/C11H13F2N.ClH/c12-7-10(8-14)2-1-9-3-5-11(13)6-4-9;/h3-7H,1-2,8,14H2;1H/b10-7+;
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| Chemical Name |
(2E)-2-(fluoromethylidene)-4-(4-fluorophenyl)butan-1-amine;hydrochloride
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| Synonyms |
MDL 72974A MDL72974A MDL-72974A
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~110 mg/mL (~470.71 mM)
H2O : ~25 mg/mL (~106.98 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (11.77 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 27.5 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: ≥ 2.75 mg/mL (11.77 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 27.5 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. View More
Solubility in Formulation 3: ≥ 2.75 mg/mL (11.77 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10 mg/mL (42.79 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2792 mL | 21.3959 mL | 42.7917 mL | |
| 5 mM | 0.8558 mL | 4.2792 mL | 8.5583 mL | |
| 10 mM | 0.4279 mL | 2.1396 mL | 4.2792 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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