In vitro activity: Ciforadenant (also known as CPI-444 and V81444) is a potent, selective and orally bioactive small molecule inhibitor of the adenosine-A2a receptor (A2AR) on T-lymphocytes. Ciforadenant is currently in a Phase I clinical trial as a single agent and in combination with atezolizumab, a PD-L1 inhibitor against various solid tumors. Ciforadenant is able to induce antitumor responses. Upon oral administration, Ciforadenant binds to adenosine A2A receptors expressed on the surface of immune cells, including T-lymphocytes, natural killer (NK) cells, macrophages and dendritic cells (DCs), which prevents tumor-released adenosine from interacting with the A2A receptors on these key immune surveillance cells, thereby abrogating adenosine-induced immunosuppression in the tumor microenvironment.

Kinase Assay: Ciforadenant (also known as CPI-444 and V81444) is a potent, selective and orally bioactive small molecule inhibitor of the adenosine-A2a receptor (A2AR) on T-lymphocytes.

Cell Assay: CPI-444 is a potent, oral, selective A2AR antagonist. CD8+ T cell depletion abrogates 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 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 CPI-444, including GITR, OX40, and LAG3 on tumor infiltrating lymphocytes and circulating T cells, suggesting a broad role for adenosine mediated immunosuppression.