Pomalidomide-¹⁵N,¹³C₅  (Synonyms: 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.

Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs^[1].
Pomalidomide also inhibits Whole Blood TNF-α with IC₅₀ of 25 nM^[2]. Exposure of lymphoma cells to Pomalidomide (CC-4047) leads to 40% decrease in cell proliferation when compared with vehicle-treated controls. Pomalidomide inhibits by 40% the DNA synthesis of Raji cells (P=0.036)^[3]. In both CD4⁺ and CD8⁺ cells, Pomalidomide (CC-4047) is the most potent IL-2-elevator, followed by CC-6032 and CC-5013. Pomalidomide is significantly more potent than CC-5013 at elevating IL-2, IL-5, and IL-10, and slightly more potent than CC-5013 at elevating IFN-γ^[4].

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

The administration of Pomalidomide (CC-4047) for two consecutive days before mAb therapy enhances the antitumor activity of Rituximab and doubled the median survival of lymphoma-bearing mice. Statistically, significant differences are observed between animals treated with Rituximab versus Pomalidomide+Rituximab. The median survival time of animals treated with Pomalidomide and Rituximab is longer (median survival, 74 days; 95% CI, 70-78) than those treated with Rituximab monotherapy (median survival, 38 days; 95% CI, 26-50; log-rank test, P=0.002). The administration of CC-5013 or Pomalidomide for two consecutive days leads to a significant increase in the number of circulating NK cells as shown by flow cytometry analysis, in lymphoma-bearing SCID mice^[3]. Following a 50 mg/kg PO administration of Pomalidomide (POM) to rats, unbound concentrations in blood reach a C_max value of 1100±82 ng/mL at 4.6±2.4 hours, with a concomitant AUC_(0-10) value of 6800±2000 ng hr/mL. Unbound POM in the brain, however, has a C_max value of 430±63 ng/mL at 4.1±1.5 hours and an AUC_(0-10) value of 2700±740 ng hr/mL, giving an unbound AUC_brain to AUC_blood ratio of 0.39±0.03. These values are consistent with excellent blood-brain-barrier penetration. The results obtained in this study are consistent with those seen in a concurrent study looking at whole brain POM content following its oral administration to mice^[5].

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

274.16

C₈¹³C₅H₆N₂¹⁵NO₄

19171-19-8

O=C1N(C(C2=C1C=CC=C2N)=O)[13C]([13C]([15NH]3)=O)[13C][13C][13C]3=O

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]