Losartan Carboxylic Acid (EXP-3174)

製品コードS5980 バッチS598001

印刷

化学情報

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

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <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の活性カルボン酸代謝物であるLosartan Carboxylic Acid (E-3174, EXP-3174) は、非ペプチド性のアンジオテンシンII (AT1) 受容体拮抗薬です。Losartan Carboxylic Acidは、[125I]-アンジオテンシンIIのVSMCへの特異的結合をIC50 1.1 nMで阻害します。
in vitro	Losartan Carboxylic Acid (EXP-3174) competes in vitro with the binding of angiotensin II to AT1 receptors, with an IC50 of 20 nmol/L. It increases AMPK phosphorylation in a time- and dose-dependent manner in VSMCs, as well as ACC phosphorylation—a major downstream target protein in the AMPK signaling cascade—and LKB1 phosphorylation, an upstream kinase of AMPK. This compound also elevates p53 and p21 expression in a time-dependent manner, while p27 levels remain unchanged. It suppresses Ang II-induced Rb phosphorylation, along with cyclin D and cyclin E expression, which are essential for cell cycle progression. The mechanism of growth suppression by losartan involves G0/G1 cell cycle arrest, reversible through AMPK inhibition (e.g., compound C or AMPK siRNA), but not via apoptosis.
in vivo	Losartan has a major active metabolite, EXP 3174. Administered intravenously, this compound is 10 to 20 times more potent than losartan and has a longer duration of action. 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. Treatment with losartan ameliorates the loss in the number and function of endothelial progenitor cells (EPCs) in hypertensive rats.

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	In the presence or absence of indicated concentrations of Losartan Carboxylic Acid (EXP-3174), cells were treated with Ang II or 15% FBS 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

参考

https://pubmed.ncbi.nlm.nih.gov/8385175/
https://pubmed.ncbi.nlm.nih.gov/11171802/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997415/

https://pubmed.ncbi.nlm.nih.gov/18250561/

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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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