CPI-444 是一种选择性的，可口服的 A2A 受体 (A2AR) 拮抗剂，可诱导抗肿瘤反应。

CPI-444 is an antagonist of the adenosine A2A receptor.It reduces tumor area in mouse model of murine Her2/neu-expressing breast cancer.

CPI-444 is a potent, oral, selective A2AR antagonist that has been well tolerated in Ph 1/1b studies in non-oncology indications.?CPI-444 is being investigated in a Ph 1b study in solid tumors as a single agent and in combination with the anti-PD-L1 antibody atezolizumab.?In preclinical studies, daily treatment of the syngeneic mouse model MC38 with CPI-444 (1, 10, 100 mg/kg) led to dose-dependent inhibition of tumor growth, leading to tumor elimination in ～30% of treated mice.?Combining CPI-444 (100 mg/kg, qd, 14 days) with anti-PD-L1 (200 μg, 3qw, 4 doses) treatment in MC38 models synergistically inhibited tumor growth and eliminated tumors in 90% of treated mice.?When cured mice were later re-challenged with MC38 cells, tumor growth was rejected in 100% of challenged mice, indicating that CPI-444 induced systemic anti-tumor immune memory.?CD8+ T cell depletion abrogated the efficacy of CPI-444 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 CPI-444 ± anti-PD-L1 was 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[1].

1202402-40-1

C20H21N7O3

407.434

ciforadenant;V81444

DMSO:67.5 mg/mL (165.67 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years