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.
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.
Molecular Weight | 407.43 |
Formula | C20H21N7O3 |
CAS Number | 1202402-40-1 |
Solubility (25°C) | 80 mg/mL in DMSO |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
Related Adenosine Receptor Products |
---|
LUF5519
LUF5519 is a ribose-containing adenosine A1 receptor agonist. |
LUF6258
LUF6258 is a hybrid ortho/allosteric ligand of the adenosine A(1) receptor. |
A3AR agonist 1
A3AR agonist 1 is an A3AR agonist (Ki: 25.8 nM). |
A3AR agonist 2
A3AR agonist 2 a selective A3AR agonist (Ki: 22.1 nM). |
Inupadenant hydrochloride
Inupadenant (EOS-850) hydrochloride is an orally active, highly selective A2A receptor antagonist. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.