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.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 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 resveratrol of 11.2 mg/kg.
|Solubility||125 mg/mL in DMSO|
Androgen Receptor Antagonists and Anti-Prostate Cancer Activities of Some Newly Synthesized Substituted Fused Pyrazolo-, Triazolo- and Thiazolo-Pyrimidine Derivatives
Bahashwan SA, et al. Int J Mol Sci. 2014 Nov 24;15(11):21587-602. PMID: 25421248.
Synthesis and antimicrobical evaluation of a novel class of 1,3,4-thiadiazole: derivatives bearing 1,2,4-triazolo[1,5-a]pyrimidine moiety.
Luo Y, et al. Eur J Med Chem. 2013 Jun;64:54-61. PMID: 23644188.
|Related Adenosine Receptor Products|
Regadenoson is an A2A adenosine receptor agonist that is a coronary vasodilator that is commonly used in pharmacologic stress testing.
ZM-241385 is a high affinity antagonist ligand selective for the adenosine A2A receptor.
CGS 21680 is a selective adenosine receptor agonist for A2A and A3 with Ki of 15 ng/mL and 37 ng/mL, respectively.
Istradefylline is a selective adenosine A2A receptor (A2AR) antagonist with Ki of 2.2 nM.
|CGS 21680 hydrochloride
CGS 21680 hydrochloride is an A2A adenosine receptor agonist with an Ki of 27 nM.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.