Enalaprilat Dihydrate

製品コードS1657 バッチS165702

化学情報

	Synonyms	MK-422 Dihydrate	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₈H₂₄N₂O₅.2H₂O
	分子量	348.4	CAS No.	84680-54-6
Solubility (25°C)*	体外	DMSO	70 mg/mL (200.91 mM)
		Water	5 mg/mL (14.35 mM)
		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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Enalaprilat (MK-422) is an angiotensin-converting enzyme (ACE) inhibitor with IC50 of 1.94 nM.
in vitro	Enalaprilat has high affinity for human endothelial ACE with IC50 of 1.94 nM in vitro binding assay by displacing a saturating concentration of [^125I]351A, a radiolabeled lisinopril analogue from ACE binding sites, and shows bradykinin/angiotensin I selectivity ratio of 1.00 calculated from double displacement experiments. ^[1] Enalaprilat has the strong inhibitory effect on Aβ42-to-Aβ40-converting activity found in the N-domain of ACE, exhibiting a 10-fold lower IC50 (0.003~0.01 μM) than captopril (0.03~0.1 μM). ^[2] Enalaprilat (100 nM) blocks protein kinase C epsilon by directly activating bradykinin B1 receptor at the canonical Zn²⁺ binding site, leading to prolonged nitric oxide (NO) production in cytokine-treated human lung microvascular endothelial cells. ^[3] Enalaprilat attenuates the IGF-I induced neonatal rat cardiac fibroblast growth (30% reduction) in a concentration-dependent fashion, with IC50 of 90 mM. ^[4]
in vivo	Enalaprilat has unfavourable ionisation characteristics to allow sufficient potency for oral administration, thus Enalaprilat is only suitable for intravenous administration, which is overcome by the esterification with ethanol to produce Enalapril. Administration of Enalaprilat induces a significant reduction of MAP at 70 minutes compared with the placebo group during haemorrhagic shock in rats, and results in a 50% reduction of CO, a general tendency of EB extravasation which is significant in the kidney and lungs, and a significant increase in ileal EB extravasation (53%). ^[5] Enalaprilat has no effect in nonhypertrophied hearts, but significantly attenuates the greater increase in left ventricular end-diastolic pressure in hypertrophied hearts compared with no drug. ^[6]
特徴	The 1st dicarboxylate-containing ACE inhibitor developed to overcome captopril limitations.

プロトコル(参考用のみ)

キナーゼアッセイ	Single displacement binding assay
キナーゼアッセイ	The binding assay is based on the competitive displacement of [^125I]351A by Enalaprilat performed on whole endothelial cells. Subconfluent HUVECs in 6-well plates are rinsed with 2 mL binding buffer (140 mM NaCl, 2.7 mM KCl, 1.8 mM CaCl₂, 1.03 mM MgCl₂, 0.42 mM NaH₂PO₄, 10 mM HEPES, 2 mM sodium pyruvate and 5 mM glucose, pH 7.4), and the culture medium is replaced with 2.5 mL fresh binding buffer containing 5% fetal bovine serum (FBS). The Enalaprilat (2.5-12.5 μL, 0.1-50 nM) or equivalent volumes of diluent are added to the binding buffer. A saturating amount of [^125I]351A (10 μL, typically 10⁶ cpm) is then added to each sample and the plates are incubated at 37 °C for 2 hours in a thermostatic bath. The cells are then rinsed twice with 1.5 mL binding buffer. Finally, the cells are extracted with 0.5 mL NaOH 1 N, incubated for 5 minutes, and the radioactivity is counted with a gamma counter. The ratio of specific [^125I]351A bound to total bound activity (B/B0) is calculated, and the inhibitory potency of Enalaprilat expressed as the concentration of ACE inhibitors able to displace 50% of the bound radioligand, i.e. the IC50.
細胞アッセイ	細胞株	Rat cardiac fibroblasts cell lines
	濃度	Dissolved in DMSO, final concentrations 1 nM - 10 μM
	反応時間	24 hours
	実験の流れ	After 24 hours incubation in serum-free medium (DMEM), cells are stimulated with IGF-I (1-100 nM) and coincubated with Enalaprilat (1 nM-10 μM) for 24 hours. Cellular proliferation is assessed by 5-bromo-2'-deoxyuridine (BrdU) incorporation during the last 4 hours of the 24 hours incubation period using a colorimetric immunoassay. The extinctions are measured at 450 nm in an ELISA plate reader. All values consist of an n=9.
動物実験	動物モデル	Male Sprague–Dawley rats
	投薬量	1 mg/kg
	投与方法	I.V. bolus

参考

+ 展开

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Pulmonary midkine inhibition ameliorates sepsis induced lung injury [ J Transl Med, 2021, 19(1):91]	PubMed: 33639987
Establishment of a Drug Screening Model for Cardiac Complications of Acute Renal Failure [ Biomolecules, 2021, 11(9)1370]	PubMed: 34572583
Functional Study of Carboxylesterase 1 Protein Isoforms. [ Proteomics, 2019, 19(4):e1800288]	PubMed: 30520264
A Comprehensive Functional Assessment of Carboxylesterase 1 Nonsynonymous Polymorphisms. [ Drug Metab Dispos, 2017, 45(11):1149-1155]	PubMed: 28838926
Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation. [ Drug Metab Dispos, 2016, 44(4):554-9]	PubMed: 26817948

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。