Losartan Carboxylic Acid (EXP-3174)

製品コードS5980 バッチS598001

印刷

化学情報

Chemical Structure Synonyms E-3174 Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C22H21ClN6O2
分子量 436.89 CAS No. 124750-92-1
Solubility (25°C)* 体外 DMSO 87 mg/mL (199.13 mM)
Ethanol 87 mg/mL (199.13 mM)
Water 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 Losartan Carboxylic Acid (E-3174, EXP-3174), an active carboxylic acid metabolite of Losartan, is a non-peptide angiotensin II (AT1) receptor antagonist. Losartan Carboxylic Acid inhibits the specific binding of [125I]-angiotensin II to VSMC with IC50 of 1.1 nM.
in vitro

In vitro, losartan competes with the binding of angiotensin II to AT1 receptors; the concentration that inhibits 50% of the binding of angiotensin II (IC50) is 20 nmol/L[2]. Losartan increases AMPK phosphorylation in a time- and dose-dependent manner in VSMCs. It also increases ACC phosphorylation, a major downstream target protein in the AMPK signaling cascade, and LKB1 phosphorylation, which is an upstream kinase of AMPK. Losartan increases p53 and p21 expression in a time-dependent manner, whereas the levels of p27 are not changed. Losartan suppresses Ang II-induced Rb phosphorylation, as well as cyclin D and cyclin E expression which are required for cell cycle progression. The mechanism of growth suppression by losartan is therefore G0/G1 cell cycle arrest which is reversed by AMPK inhibition, such as compound C or AMPK siRNA, but not by apoptosis[3].
in vivo

Losartan has a major active metabolite, EXP 3174. Administered intravenously, EXP3174 is 10 to 20 times more potent than losartan and has a longer duration of action than losartan. However, the oral bioavailability of EXP 3174 is very low. Losartan has a bioavailability of about 33%, the half-life averages 2 h (6-9 hours), and the rate of protein binding is 98.7% when dosed at 50-100 mg/d[2]. Treatment with losartan ameliorates the loss in the number and function of endothelial progenitor cells (EPCs) in hypertensive rats[4].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 VSMCs
濃度 0, 1, 5, 10 μM
反応時間 48 h
実験の流れ

Cells were treated with Ang II or 15% FBS in the presence or absence of indicated concentration of losartan for 48 hrs. Cell proliferation was determined by the MTT assay.
動物実験 動物モデル 12-week-old male Wistar-Kyoto (WKY) rats and SHR-SP
投薬量 10 mg/kg/day
投与方法 oral

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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