ST034307 is a selective AC1 inhibitor with IC50 value of 2.3μM for inhibition of A23187-stimulated cAMP accumulation in HEK cells stably expressing AC1. Also it inhibited Ca2+-stimulated cAMP accumulation by AC1, as well as inhibited AC1 activity stimulated by Gas-coupled receptors in HEK-AC1 cells. It showed inhibitory activity in multiple AC1-containing membrane preparations at 100μM and mouse hippocampal homogenates at 30μM. ST034307 enhanced m-opioid receptor (MOR)–mediated inhibition of AC1 in short-term inhibition assays in HEK-AC1 cells stably transfected with MOR, with EC20 value of 0.5μM and DAMGO (4nM) and EC20 value of 7.5μM and DAMGO (15nM). However, it blocked heterologous sensitization of AC1 caused by chronic MOR activation. Intrathecal injection with 0.5μg ST034307 reduced pain responses in a mouse model of inflammatory pain. ST034307 potentiated PMA–stimulated cAMP production by AC2 and slightly potentiated forskolin-stimulated AC5 and AC6[2].
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