Cerivastatin-d₃ sodium  (Synonyms: 西立伐他汀钠-d₃)

Cerivastatin-d₃ sodium is deuterated labeled Cerivastatin sodium (HY-109523). Cerivastatin sodium is a synthetic lipid-lowering agent and a highly potent, well-tolerated and orally active HMG-CoA reductase inhibitor, with a Ki of 1.3 nM/L. Cerivastatin sodium reduces low-density lipoprotein cholesterol levels. Cerivastatin sodium also inhibits proliferation and invasiveness of MDA-MB-231 cells, mainly by RhoA inhibition, and has anti-cancer effect^[1][2].

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]。
Cerivastatin sodium (5-50 ng/mL；3 天；MDA-MB-231 细胞) 处理诱导 MDA-MB-231 细胞增殖的剂量依赖性降低 (在 25 ng/mL 时抑制高达 40%)^[2]。
Cerivastatin sodium (25 ng/mL；18-36 小时；MDA-MB-231 细胞) 处理 36 小时后诱导细胞周期停滞在 G 1/S 期.较短的孵育时间 (18 小时) 未观察到这种停滞^[2]。
Cerivastatin sodium (25 ng/mL；18 小时；MDA-MB-231 细胞) 处理诱导显著的 p21^Waf1/Cip1 水平增加^[2]。
Cerivastatin sodium (25 ng/mL；12 小时；MDA-MB-231 细胞) 处理增加MDA-MB-231 细胞中的 p21 转录本^[2]。
Cerivastatin sodium (10-25 ng/mL；18 小时) 通过 Matrigel 抑制 MDA-MB-231 细胞的侵袭^[2]。
Cerivastatin sodium (25 ng/mL；18-36 小时) 使 RhoA 和 Ras 从细胞膜离域到胞质溶胶并诱导形态学变化^[2]。
Cerivastatin sodium (25 ng/mL；4-36 小时) 以 RhoA 抑制依赖性方式诱导 NFκB 失活，导致尿激酶和金属蛋白酶 9 表达降低，同时增加 IκB^[2]。

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

Cerivastatin sodium 吸收良好，在口服给药后 1-3 小时内达到最大血浆浓度。在循环中，Cerivastatin sodium 与血浆蛋白高度结合 (99.5%)，消除半衰期为 2-4 小时。Cerivastatin sodium 主要在肝脏中代谢为三种极性代谢物。其中两种代谢物具有活性，但与母体药物相比程度较小，第三种代谢物无活性。所有代谢物的血浆浓度都大大低于母体药物的血浆浓度。代谢物通过尿液 (20-25%) 和粪便 (66-73%) 消除，而基本上没有母体化合物排出^[3]。

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

484.55

C₂₆H₃₀D₃FNNaO₅

916314-45-9

西立伐他汀钠-d₃

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]. Denoyelle C, et al. Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits the signaling pathways involved in the invasiveness and metastatic properties of highly invasive breast cancer cell lines: an in vitro study. Carcinogenesis. 2001 Aug;22(8):1139-48.  [Content Brief]

  [3]. Stein E, et al. Cerivastatin, a New Potent Synthetic HMG Co-A Reductase Inhibitor: Effect of 0.2 mg Daily in Subjects With Primary Hypercholesterolemia. J Cardiovasc Pharmacol Ther. 1997 Jan;2(1):7-16.  [Content Brief]

  [4]. Furberg CD, et al. Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med. 2001;2(5):205-207.  [Content Brief]