PDE5-IN-3 (compound 11j) is a potent PDE5 inhibitor with an IC 50 of 1.57 nM. PDE5-IN-3 shows moderate EGFR inhibition with IC 50 of 5.827 µM. PDE5-IN-3 significantly inhibits the Wnt/β-catenin pathway (IC 50 =1286.96 ng/mL). PDE5-IN-3 induces the intrinsic apoptotic mitochondrial pathway in HepG2 cells. PDE5-IN-3 has strong antitumor activity.