Inhibition of dipeptidyl peptidase IV by fexofenadine: Virtual screening study

ABSTRACT

Dipeptidyl peptidase IV (DPP IV) is relatively new anti-diabetic target. DPP IV inhibitors lower fasting andpostprandial glucose concentrations by preventing the degradation of the natural hypoglycemic incretin hormonesglucose-dependent insulinotropic peptide and glucagon-like peptide-1. In this work, the high throughput dockingsoftware FRED was used as a virtual screening tool against in house built drug database to discover new DPP IVinhibitors. One of the highest ranking hits, the antihistamine drug fexofenadine, was found to inhibit recombinanthuman DPP IV in vitro with IC50 = 4.6 (±1.0) µM. The anti-diabetic effect of fexofenadine was validated in vivo byoral glucose tolerance test. These results could be helpful in the development of novel DPP IV inhibitors based onfexofenadine scaffold for the treatment of type 2 diabetes.