| Size | Price | |
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| 500mg | ||
| 1g | ||
| Other Sizes |
Nepicastat (SYN-117 and RS-25560-197) is a potent and selective inhibitor of both bovine and human dopamine-β-hydroxylase with IC50 of 8.5 nM and 9 nM, with negligible affinity for twelve other enzymes and thirteen neurotransmitter receptors. Dopamine beta-hydroxylase is an enzyme that catalyzes the conversion of dopamine to norepinephrine.Nepicastat has been studied as a possible treatment for congestive heart failure, and appears to be well tolerated.
| ln Vivo |
A dose-dependent reduction in norepinephrine, an increase in dopamine, and a dopamine/norepinephrine ratio in arteries (mesenteric or renal arteries) are produced by nepirestat (3–100 mg/kg; PO; three times 12 hours apart) [3].
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| Animal Protocol |
Animal/Disease Models: 15-16weeks old male spontaneously hypertensive rats (SHRs) [3] Usage and
Doses: po (po (oral gavage)) three consecutive doses, 12 hrs (hrs (hours)) apart: 3, 10, 30, 100 mg/kg Experimental Results: Arterial (mesenteric or There was a dose-dependent decrease in norepinephrine content and an increase in dopamine content and an increase in the dopamine/norepinephrine ratio in the kidney), left ventricle, and cerebral cortex. |
| References |
[1]. Beliaev A, et al. Synthesis and biological evaluation of novel, peripherally selective chromanyl imidazolethione-based inhibitors of dopamine beta-hydroxylase.J Med Chem. 2006 Feb 9;49(3):1191-7.
[2]. Stanley WC, et al. Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine-beta-hydroxylase.Br J Pharmacol. 1997 Aug;121(8):1803-9. [3]. Stanley WC, et al. Cardiovascular effects of nepicastat (RS-25560-197), a novel dopamine beta-hydroxylase inhibitor. J Cardiovasc Pharmacol. 1998 Jun;31(6):963-70. [4]. Sabbah HN, et al. Effects of dopamine beta-hydroxylase inhibition with nepicastat on the progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure. |
| Additional Infomation |
Nepicastat is a member of the class of 1,3-dihydroimidazole-2-thiones that is 1,3-dihydro-2H-imidazole-2-thione in which one of the nitrogens is substituted by a 5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl group while the carbon adjacent to it is substituted by an aminomethyl group (the S enantiomer). It is a potent and selective inhibitor of both bovine and human dopamine beta-hydroxylase, an enzyme that catalyzes the conversion of dopamine to norepinephrine. It has a role as an EC 1.14.17.1 (dopamine beta-monooxygenase) inhibitor. It is a member of tetralins, an organofluorine compound, a primary amino compound and a member of 1,3-dihydroimidazole-2-thiones.
Nepicastat has been investigated for the treatment of Cocaine Dependence and Posttraumatic Stress Disorder. |
| Molecular Formula |
C14H15N3F2S
|
|---|---|
| Molecular Weight |
295.3508
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| Exact Mass |
295.095
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| CAS # |
173997-05-2
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| Related CAS # |
Nepicastat hydrochloride;170151-24-3
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| PubChem CID |
9796181
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
401.8±55.0 °C at 760 mmHg
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| Flash Point |
196.8±31.5 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.665
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| LogP |
2.31
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
429
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| Defined Atom Stereocenter Count |
1
|
| SMILES |
FC1=CC(F)=C2CC[C@@H](CC2=C1)N3C(CN)=CNC3=S
|
| InChi Key |
YZZVIKDAOTXDEB-JTQLQIEISA-N
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| InChi Code |
InChI=1S/C14H15F2N3S/c15-9-3-8-4-10(1-2-12(8)13(16)5-9)19-11(6-17)7-18-14(19)20/h3,5,7,10H,1-2,4,6,17H2,(H,18,20)/t10-/m0/s1
|
| Chemical Name |
4-(aminomethyl)-3-[(2S)-5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]-1H-imidazole-2-thione
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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 : ≥ 48 mg/mL (~162.52 mM)
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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 | 3.3858 mL | 16.9291 mL | 33.8581 mL | |
| 5 mM | 0.6772 mL | 3.3858 mL | 6.7716 mL | |
| 10 mM | 0.3386 mL | 1.6929 mL | 3.3858 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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