FCPR03 is a selective inhibitor of phosphodiesterase 4 (PDE4) with IC50s of 31 nM, 47 nM, and 60 nM for PDE4B1, PDE4D7, and PDE4 catalytic domain, respectively. FCPR03 has neuroprotective, anti-inflammatory, and antidepressant-like effects.

PDE4B1:31 nM (IC50), PDE4D7:47 nM (IC50), PDE4 catalytic domain:60 nM (IC50)

FCPR03 displays at least 2100-fold selectivity over other PDEs (PDE1-3 and PDE5-11). In HT-22 cells, FCPR03 (5, 10, and 20 μM) increases cell viability under the oxygen-glucose deprivation (OGD) induced condition in a dose-dependent manner. FCPR03 (20 μM) increases the levels of phosphorylated AKT, GSK-3β, and β-catenin. FCPR03 (20 μM) protects against OGD-induced cellular apoptosis in both HT-22 cells and cortical neurons. The levels of mitochondrial membrane potential (MMP) and ROS are restored by FCPR03. FCPR03 (10 μM) shows significant protective effects[2].

In adult male Sprague-Dawley rats following cerebral ischemia-reperfusion, FCPR03 increases the levels of phosphorylated AKT, GSK3β and β-catenin within the ischemic penumbra. In rats following MCAO, FCPR03 (1.25, 2.5, 5 mg/kg; i.p.) reduces the infarct volume and improves neurobehavioral outcomes[2].