| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Targets |
U-0521 specifically targets catechol-O-methyltransferase (COMT), an enzyme responsible for the methylation of catecholamines (dopamine, norepinephrine, epinephrine) and catecholestrogens. By competitively binding to the active site, it prevents the transfer of a methyl group from S-adenosylmethionine (SAM) to the catechol substrate. This inhibition leads to increased levels of catecholamines in synaptic clefts and tissues. It shows selectivity for the soluble form of COMT (S-COMT) over the membrane-bound form (MB-COMT) to some extent, though it is less potent than entacapone. Its primary use is to modulate dopaminergic transmission in experimental models of Parkinson's disease and depression.
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| ln Vitro |
U-0521 has an IC50 of 6 x10-6 M and suppresses RBC COMT activity in a dose-dependent manner[1].
In vitro, U-0521 inhibits COMT activity with an IC50 of approximately 10 µM in rat liver and brain homogenates. It effectively prevents the O-methylation of dopamine and DOPA, as demonstrated in various enzyme assays. When added to neuronal cultures, it increases the extracellular concentration of dopamine by reducing its metabolism, thereby potentiating dopaminergic signaling. It has also been shown to enhance the anti-proliferative effects of catecholestrogens in cancer cell lines by inhibiting their methylation and subsequent inactivation. Its inhibitory effect is reversible and competitive with respect to the catechol substrate. |
| ln Vivo |
U-0521 (ip; 0-250 mg/kg; 10 minutes) inhibits COMT activity in a dose-dependent manner. Enzyme activity can be inhibited by 50% at 90 mg/kg, and maximum inhibition of 90% can be achieved at 250 mg/kg [1].
In vivo, U-0521 has been administered to rodents to study its effects on behavior and neurochemistry. For example, when given intraperitoneally (20-50 mg/kg), it increases brain dopamine levels and potentiates the locomotor-stimulating effects of L-DOPA. In animal models of depression, it has shown antidepressant-like activity by increasing central noradrenergic and dopaminergic transmission. However, its short half-life and limited blood-brain barrier penetration limit its utility compared to newer COMT inhibitors. In cardiovascular studies, it potentiates the vasoconstrictor effects of norepinephrine by preventing its metabolic clearance. |
| Enzyme Assay |
The inhibitory activity of U-0521 is assessed using a standard COMT enzyme assay. Typically, COMT (purified from rat liver or recombinant) is incubated with a catechol substrate (e.g., 3,4-dihydroxybenzoic acid or dopamine) and S-adenosylmethionine (SAM) as the methyl donor. The reaction is carried out at 37°C in Tris buffer at pH 7.4. Varying concentrations of U-0521 are added, and the formation of the methylated product (e.g., 3-O-methyl-dopamine or vanillic acid) is measured by HPLC with electrochemical or UV detection. The IC50 or Ki is calculated from the inhibition curve. For kinetic analysis, substrate and SAM concentrations are varied to determine the mode of inhibition.
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| Cell Assay |
In cellular models, U-0521 is used to study COMT activity in intact cells, such as SH-SY5Y neuroblastoma cells or primary cortical neurons. Cells are pre-incubated with U-0521 (10-100 µM) for 30 minutes, then exposed to a catecholamine (e.g., dopamine) for a defined period. The extracellular levels of dopamine and its methylated metabolites (3-methoxytyramine) are quantified by HPLC or ELISA. The reduction in metabolite formation indicates effective COMT inhibition. Additionally, changes in cellular signaling pathways (e.g., cAMP or ERK) downstream of dopamine receptors can be measured to assess functional consequences of the increased dopamine availability.
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| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (180-250 g) [1]
Doses: 0-250 mg/kg Route of Administration: intraperitoneal (ip) injection; 10 minutes Experimental Results: Inhibited COMT activity in a dose-dependent manner. The enzyme activity inhibition rate is 50% at 90 mg/kg, and the maximum enzyme activity inhibition rate at 250 mg/kg is 90%. In animal studies, U-0521 is typically administered via intraperitoneal injection at doses ranging from 10 to 50 mg/kg, often dissolved in saline or DMSO. For behavioral pharmacology, mice or rats are treated prior to behavioral testing (e.g., open-field test or forced swim test). For neurochemical measurements, animals are sacrificed at specific time points, and brain regions (striatum, prefrontal cortex) are dissected and homogenized. Dopamine and its metabolites are extracted and analyzed by HPLC-ECD. The effect of U-0521 on the pharmacokinetics of co-administered L-DOPA is also assessed by measuring plasma and brain levels of L-DOPA and its metabolites. |
| ADME/Pharmacokinetics |
U-0521 is rapidly absorbed after intraperitoneal administration but undergoes extensive first-pass metabolism, resulting in a short half-life (approximately 30-60 minutes in rats). Its bioavailability is low when given orally (<10%). It is primarily metabolized by conjugation and eliminated in urine. Its brain penetration is limited due to the presence of a catechol moiety, which is subject to efflux transport and rapid methylation. However, at higher doses, sufficient brain concentrations can be achieved to inhibit COMT. For research purposes, it is often administered via intracerebroventricular injection to bypass peripheral metabolism and achieve direct central effects.
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| Toxicity/Toxicokinetics |
U-0521 is relatively well-tolerated in animal studies at doses up to 50 mg/kg, with no severe acute toxicity reported. Chronic administration studies are limited. As a COMT inhibitor, it may potentiate the cardiovascular effects of catecholamines, leading to hypertension or tachycardia at high doses. It is not intended for human use, and its safety profile has not been systematically evaluated in clinical trials. In vitro, it shows low cytotoxicity at concentrations below 100 µM. However, like many catechols, it may undergo auto-oxidation to generate reactive quinones, which could contribute to oxidative stress.
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| References | |
| Additional Infomation |
U 0521 belongs to the acetophenone class of compounds.
U-0521 is a classic research tool first developed in the 1970s for studying catecholamine metabolism. It has been superseded by more potent and orally bioavailable COMT inhibitors like entacapone and tolcapone, which have reached clinical use for Parkinson's disease. Despite this, U-0521 remains useful in academic research due to its well-characterized pharmacology and low cost. It is often employed in combination with L-DOPA to enhance its central effects in experimental models of parkinsonism. It is not approved by any regulatory agency and is sold only for laboratory research purposes. |
| Molecular Formula |
C10H12O3
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|---|---|
| Molecular Weight |
180.20048
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| Exact Mass |
180.079
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| CAS # |
5466-89-7
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| PubChem CID |
21632
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| Appearance |
White to off-white solid powder
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| Density |
1.191g/cm3
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| Boiling Point |
372.2ºC at 760mmHg
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| Flash Point |
193.1ºC
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| Index of Refraction |
1.565
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| LogP |
1.936
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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 |
2
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| Heavy Atom Count |
13
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| Complexity |
189
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VDQLKIBLTMPAHI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H12O3/c1-6(2)10(13)7-3-4-8(11)9(12)5-7/h3-6,11-12H,1-2H3
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| Chemical Name |
1-(3,4-dihydroxyphenyl)-2-methylpropan-1-one
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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 |
| 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 : ~100 mg/mL (~554.94 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (13.87 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 25.0 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: ≥ 2.5 mg/mL (13.87 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 25.0 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: ≥ 2.5 mg/mL (13.87 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 | 5.5494 mL | 27.7469 mL | 55.4939 mL | |
| 5 mM | 1.1099 mL | 5.5494 mL | 11.0988 mL | |
| 10 mM | 0.5549 mL | 2.7747 mL | 5.5494 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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