Ciforadenant (CPI-444)

Cas No.:	1202402-40-1
Chemical Name:	(S)-7-(5-methylfuran-2-yl)-3-((6-(((tetrahydrofuran-3-yl)oxy)methyl)pyridin-2-yl)methyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine
Synonyms:	CPI-444,CPI 444,CPI444
SMILES:	NC1=NC2=C(N=NN2CC3=NC(CO[C@H]4CCOC4)=CC=C3)C(C5=CC=C(O5)C)=N1
Formula:	C20H21N7O3
M.Wt:	407.43
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	CPI-444 is a potent and selective inhibitor of A2A receptor (A2AR) induces antitumor responses.
In Vivo:	Daily treatment of the syngeneic mouse model MC38 with CPI-444 (1, 10, 100 mg/kg) leads 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 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 CPI-444 induces systemic anti-tumor immune memory[1].
In Vitro:	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[1].