| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
| Targets |
α-Methyltyrosine methyl ester HCl primarily targets tyrosine hydroxylase (TH), the rate-limiting enzyme in the catecholamine biosynthesis pathway. Tyrosine hydroxylase catalyzes the conversion of L-tyrosine to L-DOPA using tetrahydrobiopterin (BH4) as a cofactor. The compound acts as a competitive inhibitor of tyrosine hydroxylase, competing with the natural substrate L-tyrosine for binding to the enzyme's active site. This inhibition disrupts the catecholamine synthesis pathway, leading to decreased levels of dopamine, norepinephrine, and epinephrine in the body. The methyl ester prodrug form enhances oral bioavailability compared to the parent compound α-methyltyrosine, allowing more effective catecholamine depletion upon oral administration. The compound may also interact with other targets in the catecholamine pathway, though its primary and best-characterized action is inhibition of tyrosine hydroxylase. By reducing catecholamine synthesis, it serves as a valuable tool for studying the physiological roles of these neurotransmitters.
|
|---|---|
| ln Vitro |
In vitro, α-Methyltyrosine methyl ester HCl acts as a competitive inhibitor of tyrosine hydroxylase, preventing the conversion of tyrosine to dopamine. Enzyme activity assays demonstrate that the compound competes with L-tyrosine for binding to the enzyme active site, with inhibition kinetics consistent with competitive inhibition. The compound's inhibitory activity has been characterized using purified tyrosine hydroxylase or tissue homogenates containing the enzyme. In cell-based systems, treatment with the compound leads to reduced intracellular dopamine levels in catecholaminergic cell lines such as PC12 cells or SH-SY5Y cells. The methyl ester prodrug form shows improved cellular uptake compared to the parent acid, resulting in more potent inhibition of catecholamine synthesis in cell culture. The compound has been shown to prevent apoptosis stimulated by mutant α-synuclein, indicating potential neuroprotective effects in models of Parkinson's disease. It also prevents hyperactivity and the sniffing-licking-gnawing syndrome in animal models, consistent with reduced dopaminergic signaling.
|
| ln Vivo |
In vivo, α-Methyltyrosine methyl ester HCl demonstrates oral activity and can deplete catecholamines in the central and peripheral nervous systems. In rats, oral administration at doses of 200-1000 mg/kg daily for 4 weeks induces kidney damage and leads to urethral stone formation, indicating dose-dependent toxicity at high doses. The compound is used as a research tool to investigate the role of catecholamines in various physiological processes. It prevents hyperactivity, the sniffing-licking-gnawing syndrome, and anorexia in animal models, effects attributed to reduced dopaminergic transmission. The compound inhibits dopamine production and prevents apoptosis stimulated by mutant α-synuclein, suggesting potential applications in neurodegenerative disease research. As a prodrug of α-methyltyrosine, it is expected to have similar sympatholytic effects including reduction of blood pressure and depletion of catecholamine stores in sympathetic nerve terminals. These effects make it useful for studying stress responses, hypertension, and the role of the sympathetic nervous system in various disease models.
|
| Enzyme Assay |
Tyrosine hydroxylase enzyme activity assays are performed to characterize the inhibitory activity of α-Methyltyrosine methyl ester HCl. The enzyme is incubated with varying concentrations of the inhibitor and L-tyrosine substrate in the presence of the cofactor tetrahydrobiopterin (BH4). The reaction is terminated after a defined incubation period, and the production of L-DOPA is measured by HPLC with electrochemical detection or by spectrophotometric methods. Competitive inhibition is demonstrated by Lineweaver-Burk plot analysis, where the inhibitor increases the Km for L-tyrosine without affecting Vmax. The inhibitor constant Ki is determined from the data. For the parent compound α-methyltyrosine, Ki values in the low micromolar range have been reported. The methyl ester prodrug is expected to have similar inhibitory characteristics once hydrolyzed to the active form. Enzyme assays may be performed using purified tyrosine hydroxylase, tissue homogenates from brain or adrenal medulla, or cell lysates from catecholaminergic cell lines.
|
| Cell Assay |
Cell-based assays with α-Methyltyrosine methyl ester HCl are conducted in catecholaminergic cell lines such as PC12 cells (rat pheochromocytoma) or SH-SY5Y cells (human neuroblastoma). Cells are treated with the compound at various concentrations (typically 10-1000 µM) for defined periods (24-72 hours). Intracellular dopamine and other catecholamine levels are measured by HPLC with electrochemical detection or by ELISA. Catecholamine synthesis inhibition is assessed by measuring the incorporation of radiolabeled tyrosine into dopamine or by quantifying the accumulation of L-DOPA in the presence of a DOPA decarboxylase inhibitor. Cell viability is assessed using MTT or similar assays to distinguish specific effects from cytotoxicity. The compound's ability to prevent apoptosis stimulated by mutant α-synuclein is evaluated in appropriate cellular models of Parkinson's disease. The methyl ester prodrug shows improved cellular uptake compared to the parent compound, resulting in more potent inhibition of catecholamine synthesis in cell culture systems.
|
| Animal Protocol |
In vivo animal experiments with α-Methyltyrosine methyl ester HCl typically use rodent models (rats or mice). The compound is administered orally (by gavage or in diet) at doses ranging from 50-250 mg/kg for catecholamine depletion studies, though higher doses (200-1000 mg/kg) have been used in toxicity studies. Treatment duration varies from acute single-dose studies to chronic administration over several weeks. Endpoints include measurement of tissue catecholamine levels (brain, adrenal gland, heart, plasma) by HPLC, assessment of behavioral changes (locomotor activity, stereotypy, feeding behavior), and evaluation of sympathetic nervous system function (blood pressure, heart rate). In toxicity studies, organ histopathology and clinical chemistry parameters are evaluated to assess potential adverse effects. The compound has been shown to cause kidney damage and urethral calculi in rats at doses of 200-1000 mg/kg/day for 4 weeks. Researchers should carefully consider dose selection based on the specific experimental objectives and conduct appropriate toxicity assessments.
|
| ADME/Pharmacokinetics |
Pharmacokinetic properties of α-Methyltyrosine methyl ester HCl include oral bioavailability due to the methyl ester prodrug form, which enhances intestinal absorption compared to the parent acid. The compound is expected to be hydrolyzed to the active form α-methyltyrosine by esterases in the gastrointestinal tract, liver, and plasma. The active metabolite then distributes to tissues including the brain, where it inhibits tyrosine hydroxylase. Specific pharmacokinetic parameters such as half-life, Cmax, Tmax, and bioavailability have not been extensively reported in the literature for the methyl ester form. The compound is soluble in water (~25 mg/mL, ~101.75 mM) and DMSO (~9.09 mg/mL, ~37.00 mM), facilitating preparation of solutions for both in vitro and in vivo administration. For in vivo formulations, the compound can be dissolved in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% saline. Storage: powder at -20°C for 3 years, in solvent at -80°C for 6 months or -20°C for 1 month.
|
| Toxicity/Toxicokinetics |
Toxicology data indicate that α-Methyltyrosine methyl ester HCl can cause kidney damage and urethral stone formation in rats at high oral doses (200-1000 mg/kg/day for 4 weeks). The compound should be handled with appropriate safety precautions. No comprehensive toxicology profile (e.g., LD50, genotoxicity, carcinogenicity, reproductive toxicity) is available in the public domain. The compound is for research use only and is not approved for human therapeutic use. As a tyrosine hydroxylase inhibitor that depletes catecholamines, potential pharmacological effects include hypotension, sedation, and extrapyramidal symptoms at high doses. Researchers should monitor animals for signs of catecholamine depletion including reduced activity, ptosis, and hypothermia. The compound should be stored away from moisture and handled in a well-ventilated area with appropriate personal protective equipment. Disposal should follow institutional and regulatory guidelines for chemical waste.
|
| Additional Infomation |
α-Methyltyrosine methyl ester HCl is a research-grade tyrosine hydroxylase inhibitor with ≥98% purity. CAS number: 7361-31-1. Molecular formula: C11H16ClNO3. Molecular weight: 245.70. Chemical name: methyl 2-amino-3-(4-hydroxyphenyl)-2-methylpropanoate hydrochloride. Synonyms: alpha-Methyl-p-tyrosine methyl ester hydrochloride, α-Methyl-DL-tyrosine methyl ester hydrochloride, Tyrosine, alpha-methyl-, methyl ester, hydrochloride. The compound is a white to light yellow solid powder with melting point 192°C (dec.). Solubility: H2O ~25 mg/mL (~101.75 mM), DMSO ~9.09 mg/mL (~37.00 mM). Storage: powder at -20°C for 3 years, 4°C for 2 years; in solvent at -80°C for 6 months, -20°C for 1 month. The compound is a competitive inhibitor of tyrosine hydroxylase that inhibits the conversion of tyrosine to dopamine and can be used as a research tool for sympathetic nervous system studies. Not approved for clinical use; for research purposes only. The methyl ester form provides improved oral bioavailability compared to the parent compound α-methyltyrosine (metyrosine).
|
| Molecular Formula |
C11H15NO3.HCL
|
|---|---|
| Molecular Weight |
245.70264
|
| Exact Mass |
245.082
|
| CAS # |
7361-31-1
|
| PubChem CID |
11957616
|
| Appearance |
White to light yellow solid powder
|
| Boiling Point |
336.4ºC at 760 mmHg
|
| Melting Point |
192 °C (dec.)(lit.)
|
| Flash Point |
157.2ºC
|
| LogP |
2.327
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
16
|
| Complexity |
224
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(CC1=CC=C(C=C1)O)(C(=O)OC)N.Cl
|
| InChi Key |
OOVDEPZODSXAMU-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C11H15NO3.ClH/c1-11(12,10(14)15-2)7-8-3-5-9(13)6-4-8;/h3-6,13H,7,12H2,1-2H3;1H
|
| Chemical Name |
methyl 2-amino-3-(4-hydroxyphenyl)-2-methylpropanoate;hydrochloride
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
H2O : ~25 mg/mL (~101.75 mM)
DMSO : ~9.09 mg/mL (~37.00 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.91 mg/mL (3.70 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 9.1 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: ≥ 0.91 mg/mL (3.70 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 9.1 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: ≥ 0.91 mg/mL (3.70 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0700 mL | 20.3500 mL | 40.7000 mL | |
| 5 mM | 0.8140 mL | 4.0700 mL | 8.1400 mL | |
| 10 mM | 0.4070 mL | 2.0350 mL | 4.0700 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
