Losartan-d₆ hydrochloride  (Synonyms: 氯沙坦盐酸盐-d₆; DuP-753-d₆ hydrochloride)

Losartan-d₆ hydrochloride is deuterated labeled Losartan potassium (HY-17512A). Losartan potassium (DuP-753 potassium) is an angiotensin II receptor type 1 (AT1) antagonist, competing with the binding of angiotensin II to AT1 with an IC₅₀ of 20 nM.

氢、碳和其他元素的稳定重同位素已被纳入药物分子中，主要作为药物开发过程中定量的示踪剂。氘化引起了人们的关注，因为它可能影响药物的药代动力学和代谢谱^[1]。
Losartan potassium 竞争血管紧张素 II 与 AT1 受体的结合。抑制 50% 血管紧张素 II 结合的浓度 (IC₅₀) 为 20 nM^[2]。Losartan potassium (40 μM) 影响 I_SC 但阻止 ANGII 对 I_SC ^的影响[3]。Losartan potassium 显著降低子宫内膜癌细胞中 Ang II 介导的细胞增殖。与单独使用每种药物相比，Losartan potassium 和抗 miR-155 的组合具有显著更强的抗增殖作用^[4]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Losartan potassium (0.6 g/L，po) 处理的 Fbn1^C1039G/+ 小鼠显示相对于安慰剂处理的 Fbn1^{C1039G 远端空域口径减少/+} 。滴定 Losartan potassium 和普萘洛尔的剂量以达到可比较的血液动力学效果。pSmad2 核染色分析表明，Losartan potassium 拮抗 Fbn1^C1039G/+ 小鼠主动脉壁中的 TGF-β 信号传导。Losartan potassium 可以改善肺部的疾病表现，这一事件与改善的血流动力学似乎无关^[5]。Losartan potassium (10 mg/kg，动脉内注射) 使血液血管紧张素水平增加四到六倍。Losartan potassium (10 mg/kg，ip) 使血浆肾素水平增加 100 倍；血浆血管紧张素原水平降至对照的 24%；和血浆醛固酮水平没有变化^[6]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

465.41

C₂₂H₁₈D₆Cl₂N₆O

氯沙坦盐酸盐-d₆

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. Burnier, M. Angiotensin II type 1 receptor blockers. Circulation, 2001. 103(6): p. 904-12.  [Content Brief]

  [3]. Choi, C.H., et al. Angiotensin II type I receptor and miR-155 in endometrial cancers: synergistic antiproliferative effects of anti-miR-155 and losartan on endometrial cancer cells. Gynecol Oncol, 2012. 126(1): p. 124-31.  [Content Brief]

  [4]. Habashi, J.P., et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science, 2006. 312(5770): p. 117-21.  [Content Brief]

  [5]. Ashry, O., et al. Evidence for expression and function of angiotensin II receptor type 1 in pulmonary epithelial cells. Respir Physiol Neurobiol, 2014.  [Content Brief]

  [6]. Campbell, D.J., et al. Effects of losartan on angiotensin and bradykinin peptides and angiotensin-converting enzyme. J Cardiovasc Pharmacol, 1995. 26(2): p. 233-40.  [Content Brief]