| Size | Price | Stock | Qty |
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| Targets |
Etamicastat HCl targets dopamine-β-hydroxylase (DBH), the enzyme responsible for catalyzing the conversion of dopamine to norepinephrine. By inhibiting DBH, etamicastat reduces the biosynthesis of norepinephrine, a key neurotransmitter in the sympathetic nervous system. This leads to a decrease in sympathetic tone, which can lower blood pressure. The compound is peripherally selective, meaning it acts primarily outside the central nervous system, which may reduce central side effects.
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| ln Vitro |
Etamicastat inhibits the amplitude of hERG current wth an IC50 value of 44 μg/mL (141 μM)[2].
In vitro, etamicastat HCl is a potent and reversible inhibitor of dopamine beta-hydroxylase with an IC50 of 107 nM. It inhibits the amplitude of hERG current with an IC50 value of 44 μg/mL (141 μM). This indicates that at high concentrations, it may have some effect on cardiac potassium channels, but the IC50 for hERG is significantly higher than for DBH, suggesting a reasonable selectivity for the target enzyme. In cell-based assays, etamicastat can inhibit DBH activity in cells expressing the enzyme. |
| ln Vivo |
Intraperitoneally administered etamicastat (100 mg/kg) significantly lowers cardiac norepinephrine levels while concurrently raising dopamine levels [1]. Male Wistar rats given etamicastat (50 mg/kg; single oral dose) show moderate oral bioavailability (64%) and terminal elimination half-life (T1/2=3.7 h) [1].
In vivo, intraperitoneally administered etamicastat (100 mg/kg) significantly lowers cardiac norepinephrine levels while concurrently raising dopamine levels in NMRi mice. Chronic dopamine β-hydroxylase inhibition with etamicastat effectively decreases blood pressure, although it does not prevent the development of hypertension in the spontaneously hypertensive rat. Its cardiac safety profile has been evaluated in non-human primates and human volunteers. |
| Enzyme Assay |
Non-cellular in vitro assays for etamicastat HCl involve measuring its inhibition of DBH enzyme activity. A typical protocol uses purified recombinant human DBH enzyme. The enzyme is incubated with its substrate, dopamine, and varying concentrations of etamicastat HCl in a reaction buffer containing cofactors such as ascorbate and copper. The production of norepinephrine is measured using HPLC with electrochemical detection or a radiometric assay. The IC50 is determined from the concentration-response curve. For hERG inhibition, a patch-clamp assay using HEK293 cells expressing hERG channels is used.
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| Cell Assay |
Cellular assays for etamicastat HCl are performed using cell lines expressing DBH, such as neuroblastoma cells (e.g., SH-SY5Y) that can be differentiated to express the enzyme. Cells are treated with etamicastat at various concentrations for 24-48 hours. DBH activity is measured by incubating cell lysates with dopamine substrate and measuring the production of norepinephrine by HPLC. The inhibition of DBH activity is calculated relative to untreated controls. Cell viability is measured using an MTT assay to ensure that the observed effects are not due to cytotoxicity.
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| Animal Protocol |
Animal/Disease Models: NMRi mice [1]
Doses: 100 mg/kg Route of Administration: intraperitonealadministration Experimental Results: Caused a significant decrease in cardiac norepinephrine levels (36% of control), while increasing dopamine levels (850% of control) %). Animal/Disease Models: Male Wistar rat[1] Doses: 50 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: Oral administration at a dose of 10 mL/kg Experimental Results: Oral bioavailability (64%), Cmax (4.9 nM) and (T1/2=3.7 hrs (hrs (hours))). In vivo animal studies for etamicastat HCl are conducted in rodent models. In NMRi mice, etamicastat is administered intraperitoneally at 100 mg/kg. Cardiac norepinephrine and dopamine levels are measured by HPLC after sacrifice. In spontaneously hypertensive rats (SHR), etamicastat is administered orally to assess its effects on blood pressure. Blood pressure is measured using tail-cuff plethysmography. The compound's effects on heart rate and sympathetic nerve activity may also be assessed. |
| ADME/Pharmacokinetics |
Etamicastat HCl has a molecular weight of 347.81 and a molecular formula of C14H16ClF2N3OS. In male Wistar rats given etamicastat (50 mg/kg; single oral dose), it shows moderate oral bioavailability (64%) and a terminal elimination half-life (T1/2) of 3.7 hours. The Cmax after oral administration is 4.9 nM. It is a light yellow to yellow solid powder. The compound is soluble in DMSO. It is stored as a powder at -20°C for up to 3 years or at 4°C for up to 2 years.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for etamicastat HCl have been reported from preclinical and clinical studies. Its cardiac safety profile has been evaluated in non-human primates and human volunteers. The hERG IC50 is 44 μg/mL (141 μM), suggesting a reasonable safety margin for cardiac effects. As a research chemical, it is not intended for human use and is strictly for preclinical research purposes. Standard safety precautions should be followed when handling etamicastat HCl.
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| References |
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| Additional Infomation |
See also: Etamicastat (Note moved to).
Etamicastat HCl (BIA 5-453) is a potent, reversible, and peripherally selective dopamine-β-hydroxylase (DBH) inhibitor with an IC50 of 107 nM. It reduces the biosynthesis of norepinephrine and has been investigated as an oral antihypertensive agent for cardiovascular disease. Chronic DBH inhibition with etamicastat effectively decreases blood pressure. The compound has been studied in non-human primates and human volunteers. Etamicastat is not a clinically approved drug and has not entered clinical trials. Its primary application is in cardiovascular research. |
| Molecular Formula |
C14H16CLF2N3OS
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| Molecular Weight |
347.8088
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| Exact Mass |
347.067
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| CAS # |
677773-32-9
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| Related CAS # |
Etamicastat;760173-05-5
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| PubChem CID |
10450386
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.003
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
448
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1[C@H](COC2=C1C=C(C=C2F)F)N3C(=CNC3=S)CCN.Cl
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| InChi Key |
CKRDOSZCFINPAD-RFVHGSKJSA-N
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| InChi Code |
InChI=1S/C14H15F2N3OS.ClH/c15-9-3-8-4-11(7-20-13(8)12(16)5-9)19-10(1-2-17)6-18-14(19)21;/h3,5-6,11H,1-2,4,7,17H2,(H,18,21);1H/t11-;/m1./s1
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| Chemical Name |
4-(2-aminoethyl)-3-[(3R)-6,8-difluoro-3,4-dihydro-2H-chromen-3-yl]-1H-imidazole-2-thione;hydrochloride
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| Synonyms |
BIA5-453 BIA-5-453BIA 5-453 Etamicastat
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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 (e.g. under nitrogen), 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 : ~100 mg/mL (~287.51 mM)
H2O : ~16.67 mg/mL (~47.93 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.19 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 (7.19 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 (7.19 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 | 2.8751 mL | 14.3757 mL | 28.7513 mL | |
| 5 mM | 0.5750 mL | 2.8751 mL | 5.7503 mL | |
| 10 mM | 0.2875 mL | 1.4376 mL | 2.8751 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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