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Ciforadenant

CAS No. : 1202402-40-1

MCE 站：Ciforadenant

产品活性：Ciforadenant (CPI-444) 是一种有效的选择性的，具有口服活性的 A2A 受体 (A2AR) 拮抗剂，可诱导抗肿瘤反应。

研究领域：GPCR/G Protein

作用靶点：Adenosine Receptor

In Vitro: Ciforadenant is a potent, oral, selective A2AR antagonist. CD8⁺ T cell depletion abrogates the efficacy of Ciforadenant treatment as a single agent as well as in combination with anti-PD-L1, demonstrating a role for CD8⁺ T cells in mediating primary ａnd secondary immune responses. Anti-tumor efficacy of Ciforadenant±anti-PD-L1 is associated with increased CD8+ cell infiltration ａnd activation in MC38 tumor tissues, ａnd a corresponding rise in PD-1 expression on CD8⁺ T cells in the spleen. Additionally, levels of immune checkpoints are modulated by treatment with Ciforadenant, including GITR, OX40, ａnd LAG3 on tumor infiltrating lymphocytes ａnd circulating T cells, suggesting a broad role for adenosine mediated immunosuppression.

In Vivo: Daily treatment of the syngeneic mouse model MC38 with Ciforadenant (1, 10, 100 mg/kg) leads to dose-dependent inhibition of tumor growth, leading to tumor elimination in ~30% of treated mice. Combining Ciforadenant (100 mg/kg, qd, 14 days) with anti-PD-L1 (200 μg, 3qw, 4 doses) treatment in MC38 models synergistically inhibits tumor growth ａnd eliminates tumors in 90% of treated mice. When cured mice are later re-challenged with MC38 cells, tumor growth is rejected in 100% of challenged mice, indicating that Ciforadenant induces systemic anti-tumor immune memory.

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