Muvadenant fumarate (M1069) is a potent, dual antagonist of the A2A and A2B adenosine receptors, with selectivity of >100 fold against the A1 and A3 receptors.
M1069 caused a dose-dependent suppression of 5′-N-ethylcarboxamide adenosine (stable analog of adenosine)-stimulated cAMP and pCREB induction and rescue of IL-2 production (A2A readout) in assays with primary human T cells.
M1069 also suppressed VEGF production from human macrophages (A2B readout) in adenosine-rich settings.
M1069 exhibited superior suppression of protumorigenic cytokine secretion, including CXCL1, CXCL5 and granulocyte-colony stimulating factor, and the rescue of IL12 secretion from adenosine-differentiated dendritic cells, as compared to an A2Aselective antagonist.
M1069 demonstrated superior T cell activation in adenosine-differentiated dendritic cells.
M1069 reduced tumor growth as a monotherapy and enhanced anti-tumor activity with chemotherapeutic agents in a murine CD73hi/adenosine-rich 4T1 syngeneic breast tumor model.