Optimizing Therapeutics for Reducing the Side-Effects of Hypertension Treatments using Binding Kinetics

ACE inhibitors reduce blood pressure by inhibiting production of the potent vasoconstrictor angiotensin II and ARB inhibitors block binding of angiotensin II to the angiotensin receptor. Since ACE catalyzes the final step in the metabolic pathway of angiotensin II, inhibitors involved further up-stream in the metabolic pathway, such as renin inhibitors, have been sought to help reduce unwanted side effects. Despite the wealth of information, developing functional nonpeptidic inhibitors of renin has proven challenging. In this application note, structural and thermodynamic information is used to provide insights into the structure activity relationship for ligand interactions with the binding pockets.