Recent progress of the development of dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus

• Li N.
• Wang L.-J.
• Jiang B.
• Li X.-q.
• Guo C.-l.
• Guo S.-j.
• Shi D.-Y.

Abstract

Diabetes is a fast growing chronic metabolic disorder around the world. Dipeptidyl peptidase-4 (DPP-4) is a new promising target during type 2 diabetes glycemic control. Thus, a number of potent DPP-4 inhibitors were developed and play a rapidly evolving role in the management of type 2 diabetes in recent years. This article reviews the development of synthetic and natural DPP-4 inhibitors from 2012 to 2017 and provides their physico-chemical properties, biological activities against DPP-4 and selectivity over dipeptidyl peptidase-8/9. Moreover, the glucose-lowering mechanisms and the active site of DPP-4 are also discussed. We also discuss strategies and structure-activity relationships for identifying potent DPP-4 inhibitors, which will provide useful information for developing potent DPP-4 drugs as type 2 diabtes treatments.

Keywords:DPP-4, inhibitors, analogs, physico-chemical properties, SARs, type 2 diabetes