Biological Activity
VCP746 is an adenosine receptor A1 (A1AR) agonist composed of adenosine linked to the A1AR positive allosteric modulator VCP171allowing greatly improved affinity (KI = 58.9 nM vs. 2.95 μM/adenosine & 1.55 μM/VCP171) and potency (GTPγS binding induction EC50 = 0.89 nM vs. 93.3 nM/adenosine & 977 nM/VCP171; hA1AR-CHO membrane) via bitopic receptor engagement with both orthosteric and allosteric sitesas well as biased agonism toward inhibition of forskolin-stimulated cAMP over ERK1/2 phosphorylation (hA1AR-CHO) without hA3AR agonist potency. VCP746 protects against ischemia/hypoxia-induced death of r at neonatal ventricular cardiomyocytes (1 μM) and embryonic cardiomyoblasts (300 nM) without affecting isolated r at atrial heart rate.
