Pomalidomide-¹⁵N,¹³C₅  (Synonyms: 泊马度胺-¹⁵N,¹³C₅; CC-4047-¹⁵N,¹³C₅)

Pomalidomide-¹⁵N,¹³C₅ is ¹⁵N and ¹³C labeled Pomalidomide (HY-10984). Pomalidomide, the third-generation immunomodulatory agent, acts as molecular glue. Pomalidomide interacts with the E3 ligase cereblon and induces degradation of essential Ikaros transcription factors.

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]。
Pomalidomide 还抑制全血 TNF-α，IC₅₀ 为 25 nM^[2]。与载体处理的对照相比，将淋巴瘤细胞暴露于 Pomalidomide (CC-4047) 会导致细胞增殖减少 40%。Pomalidomide 抑制 Raji 细胞 40% 的 DNA 合成 (P=0.036)^[3]。在 CD4⁺ 和 CD8⁺ 细胞中，Pomalidomide (CC-4047) 是最有效的 IL-2 升高剂，其次是 CC-6032 和 CC-5013。Pomalidomide 在升高 IL-2、IL-5 和 IL-10 方面明显强于 CC-5013，在升高 IFN-γ 方面略强于 CC-5013^[4]。

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

在 mAb 处理前连续两天给予 Pomalidomide (CC-4047) 可增强利妥昔单抗的抗肿瘤活性，并使荷淋巴瘤小鼠的中位生存期增加一倍。在统计学上，观察到用 Rituximab 处理的动物与 Pomalidomide + Rituximab 处理的动物之间存在显著差异。接受 Pomalidomide 和利妥昔单抗处理的动物的中位生存时间 (中位生存期，74 天；95% CI，70-78) 长于接受利妥昔单抗单一疗法处理的动物 (中位生存期，38 天；95% CI，26-50；log-秩检验，P=0.002)。如流式细胞术分析所示，在荷淋巴瘤 SCID 小鼠中，连续两天施用 CC-5013 或 Pomalidomide 会导致循环 NK 细胞数量显著增加^[3]。对大鼠口服 Pomalidomide (POM) 50 mg/kg 后，血液中未结合的浓度在 4.6±2.4 小时时达到 1100±82 ng/mL 的 C_max 值，同时 AUC_(0-10) 值为 6800 ng hr/mL。然而，大脑中未结合的 POM 在 4.1h 时的 C_max 值为 430 ng/mL，AUC_(0-10) 值为 2700 ng hr/mL，未结合的 AUC_brain 与 AUC_blood 的比率为 0.39。这些值与出色的血脑屏障穿透力一致。本研究中获得的结果与同时进行的研究中观察到的结果一致，该研究观察了小鼠口服 POM 后的全脑内容^[5]。

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

274.16

C₈¹³C₅H₆N₂¹⁵NO₄

19171-19-8

泊马度胺-¹⁵N,¹³C₅

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]. Lu J, et al. Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4. Chem Biol. 2015 Jun 18;22(6):755-63.  [Content Brief]

  [3]. Zhu YX, et al. Molecular mechanism of action of the immune-modulatory drugs, thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk Lymphoma. 2013 Apr;54(4):683-7.  [Content Brief]

  [4]. Li Z, et al. Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models. PLoS One. 2013 Aug 5;8(8):e71754.  [Content Brief]

  [5]. Hernandez-Ilizaliturri FJ1, et al. Immunomodulatory drug CC-5013 or CC-4047 and rituximab enhance antitumor activity in a severe combined immunodeficient mouse lymphoma model. Clin Cancer Res. 2005 Aug 15;11(16):5984-92.  [Content Brief]

  [6]. Liu D, et al. Tumour necrosis factor-α inhibits hepatic lipid deposition through GSK-3β/β-catenin signaling in juvenile turbot (Scophthalmus maximus L.). Gen Comp Endocrinol. 2016 Mar 1;228:1-8.  [Content Brief]

  [7]. Schafer PH, et al. Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J Pharmacol Exp Ther. 2003 Jun;305(3):1222-32.  [Content Brief]