CPI-444

CPI-444 (CAS No.: 1202402-40-1) is a potent, orally active small-molecule antagonist of the adenosine A2A receptor (A2AR), a G protein–coupled receptor that plays a critical role in modulating immunosuppressive signaling within the tumor microenvironment. By selectively blocking A2AR-mediated adenosine signaling, CPI-444 alleviates adenosine-induced inhibition of immune cell activation, thereby enhancing antitumor immune responses. This compound has been widely characterized in cancer immunology research, where it demonstrates the ability to reduce tumor burden in preclinical models, including murine Her2/neu-expressing breast cancer systems, highlighting its relevance in studies of tumor immune evasion. CPI-444 exhibits activity in the nanomolar to low micromolar range in biochemical and cellular assays, consistent with its high affinity and selectivity for A2AR. It is commonly utilized in vitro to investigate adenosine-dependent signaling pathways and immune cell function, as well as in vivo to evaluate therapeutic strategies targeting immune checkpoint modulation and tumor progression. Experimental concentrations or dosing regimens vary depending on specific study designs, making CPI-444 a valuable tool compound for mechanistic studies and early-stage drug discovery efforts focused on adenosine receptor biology and cancer immunotherapy.