PROTAC-Mediated DPP-4 Degradation: A New Solution for Type 2 Diabetes.

Dipeptidyl peptidase-4 (DPP-4) is an important aggravating factor in the progression and exacerbation of type 2 diabetes mellitus (T2DM), a condition characterized by diminished insulin responsiveness because it rapidly degrades glucagon-like peptide-1 (GLP-1) and other peptide with similar physiological function. Although several small-molecule DPP-4 inhibitors have been developed for the clinical management of T2DM, their therapeutic benefits are only moderate, as the fail to achieve for sustained inhibition of DPP-4. Hence, targeted degradation of DPP-4 using proteolysis-targeting chimera (PROTAC) technology offers an alternative strategy for sustained glycemic control in T2DM.