| Identification | Back Directory | [Name]
(S)-7-(5-Methyl-furan-2-yl)-3-[6-(tetrahydro-furan-3-yloxyMethyl)-pyridin-2-ylMethyl]-3H-[1,2,3]triazolo[4,5-d]pyriMidin-5-ylaMine | [CAS]
1202402-40-1 | [Synonyms]
V81444
CS-2828
CPD1110
CPI-444
Ciforadenant
CPI-444 AND7648
CPI-444 (V81444)
CPI-444;CPI 444;CPI444
Ciforadenant (CPI-444)
Triazolo-pyramidine derivative
(S)-5-Amino-7-(5-methyl-2-furyl)-3-[[6-[[(3-tetrahydrofuranyl)oxy]methyl]-2-pyridyl]methyl]-3H-[1,2,3]triazolo[4,5-d]pyrimidine
(S)-3-{6-[(tetrahydrofuran-3-yloxy)methyl]pyridin-2-ylmethyl}-7-(5-methyl-2-furyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-ylamine
(S)-7-(5-Methyl-furan-2-yl)-3-[6-(tetrahydro-furan-3-yloxyMethyl)-pyridin-2-ylMethyl]-3H-[1,2,3]triazolo[4,5-d]pyriMidin-5-ylaMine
(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
7-(5-Methyl-2-furanyl)-3-[[6-[[[(3S)-tetrahydro-3-furanyl]oxy]methyl]-2-pyridinyl]methyl]-3H-1,2,3-triazolo[4,5-d]pyrimidin-5-amine
3H-1,2,3-Triazolo[4,5-d]pyrimidin-5-amine, 7-(5-methyl-2-furanyl)-3-[[6-[[[(3S)-tetrahydro-3-furanyl]oxy]methyl]-2-pyridinyl]methyl]- | [Molecular Formula]
C20H21N7O3 | [MDL Number]
MFCD31540410 | [MOL File]
1202402-40-1.mol | [Molecular Weight]
407.426 |
| Chemical Properties | Back Directory | [Melting point ]
169-171°C | [Boiling point ]
676.9±65.0 °C(Predicted) | [density ]
1.55±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (up to at least 25 mg/ml) | [form ]
solid | [pka]
4.05±0.30(Predicted) | [color ]
Beige | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| Hazard Information | Back Directory | [Description]
CPI-444 (1202402-40-1) is a potent (Ki = 3.54 nM) and selective adenosine A2A receptor antagonist. It blocked the induction of cAMP induced by NECA in HEK-293 cells with an IC50 = 17.03 nM. CPI-444 monotherapy or in combination with anti-PD-1, anti-PD-L1, and anti-CTLA-4 induced T-cell-mediated tumor responses, inhibited tumor growth, and enabled antitumor immune memory. Currently in clinical trials for multiple cancers. | [Uses]
CPI-444 is an orally administered antagonist to the A2A receptor, and binds to adenosine receptors on the surface of immune cells. | [Biological Functions]
CPI-444 is a small molecule, oral, checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by blocking the binding of adenosine in the tumor microenvironment to the A2A receptor. Adenosine, a metabolite of ATP (adenosine tri-phosphate), is produced within the tumor microenvironment where it may bind to the adenosine A2A receptor present on immune cells and block their activity. CD39 and CD73 are enzymes on the surface of tumor cells and immune cells. These enzymes work in concert to convert ATP to adenosine. In vitro and preclinical studies have shown that dual blockade of CD73 and the A2A receptor may be synergistic. | [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. | [References]
1) Willingham?et al.?(2018),?A2AR Antagonism with CPI-444 Induces Antitumor Responses and Augments Efficacy to Anti-PD-(L)1 and Anti-CTLA-4 in Preclinical Models;?Cancer Immunol. Res.?6?1136
2) Leone?et al.?(2018),?), Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models;?Cancer Immunol. Immunother.?671271
3) NCT02655822 |
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