Apalutamide-d₇  (Synonyms: ARN-509-d₇)

Apalutamide-d₇ is deuterated labeled Apalutamide (HY-16060). Apalutamide (ARN-509) is a potent and competitive androgen receptor (AR) antagonist, binding AR with an IC₅₀ of 16 nM^[1].

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]。
Apalutamide (ARN-509) 在放射配体结合试验中对 GABA_A 受体也表现出低微摩尔亲和力 (IC₅₀ 3 μM)，因此可能潜在地拮抗 GABA _A 处于抑制剂量水平^[2]。Apalutamide 是一种有效的雄激素受体 (AR) 拮抗剂，可靶向 AR 配体结合域并阻止 AR 核转位、DNA 结合和 AR 基因靶点的转录^[3]。

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

Apalutamide (ARN-509) 在小鼠和犬体内均表现出低全身清除率、高口服生物利用度和长血浆半衰期，支持每日一次口服给药。与其较长的终末半衰期一致，Apalutamide 稳态血浆水平在重复剂量研究中增加，导致高 C_24hr 水平和低峰谷比 (比率：2.5)。携带 LNCaP/AR 异种移植肿瘤的阉割雄性小鼠用 Apalutamide 以 1、10 或 30 mg/kg/day的剂量进行处理。20 只 Apalutamide (30 mg/kg/day) 处理的动物中有 13 只在第 28 天表现出 >50% 的肿瘤体积减少，而 19 只 MDV3100 (30 mg/kg/day) 处理的小鼠中有 3 只^[2]。

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

484.48

C₂₁H₈D₇F₄N₅O₂S

阿帕鲁胺-d₇

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]. Clegg NJ, et al. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012 Mar 15;72(6):1494-503.  [Content Brief]

  [3]. Smith MR, et al. Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort. Eur Urol. 2016 May 6. pii: S0302-2838(16)30133  [Content Brief]