Methods and pharmaceutical compositions for treating diseases characterized by compromised epithelial or endothelial barrier integrity are provided. The pharmaceutical compositions include an effective amount a Epac/Rap1 signaling inhibitor. The methods include administering to a patient suffering from a disease characterized by compromised epithelial or endothelial barrier integrity a therapeutically effective amount of a Epac/Rap1 signaling inhibitor, such as ESI-09, SecinH3, Slit, or AG1024.
