Nepicastat (SYN-117) HCl

製品コードS2695 バッチS269502

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C14H15F2N3S.HCl
分子量 331.81 CAS No. 170151-24-3
Solubility (25°C)* 体外 DMSO 66 mg/mL (198.9 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

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生物活性

製品説明 Nepicastat (SYN-117) HCl 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. Phase 2.
in vitro In vitro, Nepicastat hydrochloride shows the selective and concentration-dependent inhibition effects on bovine and human dopamine-beta-hydroxylase activity with IC50 of 8.5 nM and 9.0 nM, respectively. While Nepicastat hydrochloride has negligible affinity for twelve other enzymes and thirteen neurotransmitter receptors. [1]
in vivo In the artery, left ventricle and cerebral cortex of spontaneously hypertensive rats (SHRs), Nepicastat hydrochloride reduces noradrenaline content, and increases dopamine content and dopamine/noradrenaline ratio in a dose-dependent manner. In addition, Nepicastat hydrochloride also produces the similar effects on noradrenaline, dopamine and dopamine/noradrenaline ratio in tissues and plasma of beagle dogs. [1] In inactin-anesthetized SHRs, Nepicastat hydrochloride (3 mg/kg, i.v.) produces the antihypertensive effects and causes a significant decrease in renal vascular resistance (38%) and an increase in renal blood flow (22%). [2] In dogs with chronic heart failure, low-dose Nepicastat hydrochloride (0.5 mg/kg) prevents left ventricular (LV) dysfunction and remodeling, and combination therapy of Nepicastat hydrochloride and enalapril results in additional improvements in all morphological features. [3] In rat brain, Nepicastat hydrochloride at a dose of 50 mg/kg ( i.p.) leads to the reduction of norepinephrine (NE) and blocks cocaine-primed reinstatement of cocaine seeking. [4]

プロトコル(参考用のみ)

キナーゼアッセイ In vitro studies
Bovine and human dopamine-beta-hydroxylase activity are assayed by measuring the conversion of tyramine to octopamine. Human dopamine-beta-hydroxylase is purified from the culture medium of the neuroblastoma cell line SK-N-SH. The assay is performed at pH 5.2 and 32°C in a medium containing 0.125 M sodium acetate, 10 mM fumarate, 0.5 ± 2 μM CuSO4, 0.1 mg/mL catalase, 0.1 mM tyramine and 4 mM ascorbate. In a typical assay, 0.5 ± 1 mu of enzyme are added to the reaction mixture and, subsequently, a substrate mixture containing catalase, tyramine and ascorbate is added to initiate the reaction (final volume of 0.2 mL). Samples are incubated with or without the appropriate concentration of nepicastat (RS-25560-197, S-enantiomer) or RS-25560-198 (R-enantiomer) at 37 °C for 30-40 minutes. The reaction is quenched by the stop solution containing 25 mM EDTA and 240 μM 3-hydroxytyramine (internal standard). The samples are analysed for octopamine by reverse phase high pressure liquid chromatography (h.p.l.c.) with ultraviolet (u.v.)-detection at 280 nM. The h.p.l.c. run is carried out at a flow rate of 1 mL/min with a LiChroCART 125-4 RP-18 column and isocratic elution with 10 mM acetic acid, 10 mM 1-heptane sulphonic acid, 12 mM tetrabutyl ammonium phosphate and 10% methanol. The remaining % activity is calculated based on controls (without RS 25560), corrected with internal standards and fitted to a non-linear four-parameter concentration-response curve. The activity of nepicastat at twelve selected enzymes and receptors is determined by use of established assays. Binding data are analysed by iterative curve-fitting to a four parameter logistic equation. Ki values are calculated from IC50 values by the Cheng-Pruso€ equation. Enzyme inhibitory activity is expressed as IC50 (concentration required to produce 50% inhibition of enzyme activity).
動物実験 動物モデル Spontaneously hypertensive rats (SHRs).
投薬量 ≤100 mg/kg
投与方法 Administered via p.o.

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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