Discovery of Novel Adenylyl Cyclase Inhibitor by Cell-Based Screening

Abstract

We screened 2400 compounds to find novel inhibitors of the adenylyl cyclase (AC)–protein kinase A (PKA)–cAMP response-element-binding protein (CREB) signaling pathway (AC/PKA/CREB pathway). Using a multistep cell-based screening system employing split luciferase technique, we narrowed down the candidates effectively from 2400 chemical compounds and identified a novel AC inhibitor (compound 1). Since dysregulation of the AC/PKA/CREB pathway is known to cause diseases not only in the nervous system but also in other organs, compound 1 is expected to be developed as a medicine for these diseases.