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| Targets |
U-14624 targets the enzyme dopamine beta-hydroxylase (DBH). DBH is responsible for converting dopamine to norepinephrine (noradrenaline) in the catecholamine synthesis pathway. By inhibiting DBH, U-14624 prevents the formation of norepinephrine, leading to a decrease in its levels. This reduces sympathetic nervous system outflow, which can lower blood pressure and has anti-inflammatory effects. It also suppresses the activities of aminopyrine N-demethylase, aniline hydroxylase, and p-nitroanisole O-demethylase.
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| ln Vitro |
In vitro, U-14624 is a potent dopamine beta-hydroxylase inhibitor. Its activity is typically measured by incubating a source of DBH (e.g., bovine adrenal medulla homogenate) with its substrate (dopamine) in the presence of oxygen and cofactors (e.g., ascorbate, fumarate). The production of norepinephrine is quantified by HPLC, and the concentration of U-14624 that inhibits 50% of the activity (IC₅0) is determined. The exact IC₅0 value for DBH is not widely listed but is in the low micromolar range. It also suppresses other drug-metabolizing enzymes, though DBH is its primary target.
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| ln Vivo |
U-14624 (50 mg/kg; ip; daily for 5-7 days) inhibits the activities of aminopyrine N-demethylase, aniline hydroxylase and p-nitroanisole O-demethylase in rats[2].
U-14624 is an orally active compound. In vivo, it is used to suppress the conversion of dopamine to norepinephrine. This results in a lowering of norepinephrine levels in the central and peripheral nervous systems, leading to a reduction in sympathetic tone. This makes it a valuable research tool for studying hypertension, where decreased sympathetic activity can lower blood pressure. It is also used to explore the role of norepinephrine in inflammation and neurological disorders. |
| Enzyme Assay |
A standard non-cellular assay to measure DBH activity relies on the quantification of the norepinephrine product. Bovine adrenal medulla extract (source of DBH) is incubated in a buffer containing dopamine hydrochloride, ascorbic acid (as a cofactor), catalase, fumarate, and U-14624 (0.01-100 uM). After incubation at 37degC, the reaction is terminated by adding perchloric acid. The norepinephrine produced is extracted and quantified by HPLC with electrochemical detection (HPLC-ECD). The IC₅0 is calculated.
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| Cell Assay |
For cellular assays, human neuroblastoma SH-SY5Y cells, which endogenously express DBH, are used. Cells are differentiated and then treated with U-14624 (0.1-10 uM) for 24 hours. Cells are lysed, and the levels of dopamine and norepinephrine are measured by HPLC-ECD. U-14624 treatment should result in a dose-dependent decrease in norepinephrine levels and a corresponding increase in dopamine levels.
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| Animal Protocol |
Animal/Disease Models: 150-260 g, Male Sprague-Dawley rats[2]
Doses: 25 mg/kg Route of Administration: I.p.; daily for 3 days Experimental Results: Prolonged the time required for clearance of pentobarbital from both the plasma and brain, slept significantly longer. Animal/Disease Models: 150-260 g, Male Sprague-Dawley rats[2] Doses: 50 mg/kg Route of Administration: I.p.; daily for 5-7 days Experimental Results: Suppressed the activities of aminopyrine N-demethylase, aniline hydroxylase and p-nitroanisole O-demethylase enzymes. U-14624 is used to study the role of norepinephrine in cocaine addiction. Rats are trained to self-administer cocaine. The rats are then pretreated with U-14624 (orally, 0.5-20 mg/kg). The effect on cocaine-seeking behavior is measured. By inhibiting DBH and lowering norepinephrine levels, the compound can reduce the reinforcing effects of cocaine, as measured by a reduction in lever presses for cocaine. This has implications for treating substance use disorders. |
| ADME/Pharmacokinetics |
The compound has a low molecular weight (MW 235.3) and is orally active, suggesting good oral bioavailability and blood-brain barrier penetration. It is not a drug, so detailed human PK data is limited. Its half-life in rodents is likely moderate (2-6 hours), making it suitable for in vivo dosing studies. For storage, it should be kept as a powder at -20degC, protected from light. It is soluble in DMSO and ethanol.
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| Toxicity/Toxicokinetics |
U-14624 is a research chemical; its toxicological profile has not been fully characterized. As an inhibitor of catecholamine synthesis, potential side effects in research animals include sedation, hypotension, and other symptoms associated with reduced sympathetic tone. It should be handled with standard laboratory precautions (gloves, lab coat, goggles). It is not for human consumption. Keep away from strong oxidizing agents.
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| References |
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| Additional Infomation |
Dopamine β-hydroxylase inhibitor.
U-14624 is a specific chemical probe that has been instrumental in understanding the central and peripheral roles of norepinephrine. The ability to orally inhibit DBH makes it a powerful tool for behavioral studies. It is also known as "Fusaric acid analog" or "DBH Inhibitor 1". It is distinct from disulfiram, which also inhibits DBH but has other mechanisms. This product is for research use only. |
| Molecular Formula |
C10H9N3S2
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|---|---|
| Molecular Weight |
235.33
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| Exact Mass |
235.024
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| CAS # |
14901-16-7
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| PubChem CID |
719408
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.466g/cm3
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| Boiling Point |
370.8ºC at 760mmHg
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| Melting Point |
183-185 °C (dec.)(lit.)
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| Flash Point |
178.1ºC
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| Vapour Pressure |
1.08E-05mmHg at 25°C
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| Index of Refraction |
1.803
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| LogP |
3.098
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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 |
15
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| Complexity |
217
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(NC(NC2=NC=CS2)=S)C=CC=CC=1
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| InChi Key |
GCZZOZBWAZHCAN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H9N3S2/c14-9(13-10-11-6-7-15-10)12-8-4-2-1-3-5-8/h1-7H,(H2,11,12,13,14)
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| Chemical Name |
1-phenyl-3-(1,3-thiazol-2-yl)thiourea
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~50 mg/mL (~212.47 mM; with heating and sonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2494 mL | 21.2468 mL | 42.4935 mL | |
| 5 mM | 0.8499 mL | 4.2494 mL | 8.4987 mL | |
| 10 mM | 0.4249 mL | 2.1247 mL | 4.2494 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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