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Pomalidomide

CAS No. : 19171-19-8

MCE 国际站：Pomalidomide

产品活性：Pomalidomide 是第三代免疫调节剂，以分子胶的方式作用。Pomalidomide 与 E3 连接酶 cereblon 相互作用，诱导必需的 Ikaros 转录因子的降解。

研究领域：PROTAC  |  Apoptosis

作用靶点：Ligands for E3 Ligase  |  Molecular Glues  |  Apoptosis

In Vitro: Pomalidomide also inhibits Whole Blood TNF-α with IC₅₀ of 25 nM. 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). 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.

In Vivo: 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. 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.

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