Telmisartan Combination with Amlodipine Inhibits RAGE

Abstract

Diabetic Retinopathy (DR) is the leading cause of blindness in the United States corresponding to 20,000 new diagnoses annually (cite this). Hyperglycemia is a major risk factor of type 2 diabetes and leads to the formation of plasma proteins known as Advanced Glycation End Products (AGEs). In the eye, AGES’s bind to the receptor of the Advanced Glycation End Products (RAGEs) eventually leading to DR. The following study analyzed drug targets (single drugs and combination of drugs) that are currently marketed for heart disease, diabetes, and hypertension to understand how they interact with RAGE with the goal of identifying compounds that are predicted to inhibit the ligand-receptor interaction. Docking programs, AutoDock Tools and AutoDock Vina, were used to determine the binding affinity and visual orientation of the drug receptor binding. Cholesterol lowering drugs such as Atorvastatin and Fenofibrate were able to bind to RAGE with a high hydrophobicity and great negative affinity (-7.5 and -7.7). In combination, the hypertensive drugs such as Telmisartan (Angiotensin II receptor blocker) and Amlodipine (calcium channel blocker) bind with the RAGE receptor with a high hydrophobicity and high negative affinity (-9.7). Metformin administered alone or in combination was not shown to bind to RAGE. Overall this analysis shows that a combination of hypertensive drugs and cholesterol lowering drugs may decrease the progression of DR in type II diabetes. Disclosure S. Sriramoju: None. K. Goetz: None.