Alendronate-d₆ sodium hydrate  (Synonyms: 阿仑膦酸钠-d₆)

Alendronate-d₆ sodium hydrate is deuterated labeled Alendronate sodium hydrate (HY-11101). Alendronate sodium hydrate is a farnesyl diphosphate synthase inhibitor with IC₅₀ of 460 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]。
Alendronate sodium hydrate 直接作用于破骨细胞，可抑制胆固醇生物合成途径中的限速步骤，这对破骨细胞功能至关重要^[2]。由于香叶基香叶基二磷酸水平降低，Alendronate sodium hydrate 抑制类异戊二烯生物合成途径并干扰蛋白质异戊二烯化。Alendronate sodium hydrate 抑制 [³H]mevalonolactone 掺入 18-25 kDa 的蛋白质和非皂化脂质，包括破骨细胞中的甾醇^[3]。Alendronate sodium hydrate 会剂量依赖性地抑制 [³H]MVA 掺入甾醇，并伴随增加放射性标记掺入 IPP 和 DMAPP^[4]。

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

Alendronate sodium hydrate 引起兔胃糜烂，但不会引起大鼠胃窦溃疡。Alendronate sodium hydrate 增加了吲哚美辛诱发的胃窦溃疡的发生率和大小。Alendronate sodium hydrate 还会增强大鼠吲哚美辛引起的胃损伤，并延缓胃溃疡愈合^[5]。Alendronate sodium hydrate (0.04-0.1 mg/kg，每周两次或 0.1 mg/kg，每周) 部分阻断人 PC-3 ML 细胞骨转移的形成，并导致腹膜和其他软组织中的肿瘤形成。对小鼠进行 Alendronate sodium hydrate 预处理 (0.1 mg/kg，每周或每周两次) 并与紫杉醇一起给药 (10-50 mg/kg/天，每周两次或每周一次) 可阻断骨髓和软组织中 PC-3 ML 肿瘤的生长并将存活率显着提高 4-5 周^[6]。

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

331.16

C₄H₁₂D₆NNaO₁₀P₂

121268-17-5

阿仑膦酸钠-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]. Fisher JE, et al. Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):133-8  [Content Brief]

  [3]. Keller RK, et al. Mechanism of aminobisphosphonate action: characterization of alendronate inhibition of the isoprenoid pathway. Biochem Biophys Res Commun. 1999 Dec 20;266(2):560-3.  [Content Brief]

  [4]. Bergstrom JD, et al. Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase. Arch Biochem Biophys. 2000 Jan 1;373(1):231-41.  [Content Brief]

  [5]. Elliott SN, et al. Alendronate induces gastric injury and delays ulcer healing in rodents. Life Sci. 1998;62(1):77-91.  [Content Brief]

  [6]. Stearns ME, et al. Effects of alendronate and taxol on PC-3 ML cell bone metastases in SCID mice. Invasion Metastasis. 1996;16(3):116-31.  [Content Brief]