Anagliptin is a Highly Selective, Potent Inhibitor of Dipeptidyl Peptidase 4 (DPP-4)

Dipeptidyl Peptidases are widely distributed exopeptidases that possess central role in proteolysis. The dipeptidyl peptidase family, including DPP-4 DPP-7, DPP-8, DPP-9, and fibroblast activation protein. Among them, DPP-4 (CD26) is a serine protease detected on several immune cells and on epithelial cells of various organs. In addition, DPP-4 plays a key role in immune-regulation, inflammation, oxidative stress, cell adhesion, and apoptosis by targeting different substrates. Furthermore, DPP-4 is a membrane-bound exopeptidase that rapidly degrades GLP-1. Thus, DPP-4 inhibitors are theoretically useful for the treatment for type 2 diabetes by raising the concentration of GLP-1.

Anagliptin (also known as SK-0403) is a highly selective, potent and orally active dipeptidyl peptidase 4 (DPP-4) inhibitor. And Anagliptin shows higher selective for DPP-4 than DPP-8/9. Most importantly, Anagliptin has the potenial for type 2 diabetes, lipid metabolism, and atherosclerosis research. For example, in male low-density lipoprotein receptor-deficient mice, Anagliptin significantly decreases the plasma total cholesterol and triglyceride levels. In addition, Anagliptin also inhibits low-density lipoprotein cholesterol (LDL‐C) and very low-density lipoprotein cholesterol. Moreover, in HepG2 cells, Anagliptin significantly suppresses sterol regulatory element-binding protein (SREBP) activity. For atherosclerosis, in male apolipoprotein E (apoE)-deficient mice, Anagliptin can suppress proliferation of vascular smooth muscles and monocyte inflammatory reaction and attenuates atherosclerosis. In THP-1 cells, Anagliptin reduces lipopolysaccharide-induced TNF-α production with inhibiting ERK phosphorylation and nuclear translocation of NF-κB.

Taken together, Anagliptin is a selective, potent and orally active DPP-4 inhibitor primarily used in type 2 diabetes research.


[1] Nasib Ervinna, et al. Endocrinology. 2013 Mar;154(3):1260-70.

[2] Jun Hou Tan, et al. Antimicrob Agents Chemother. 2017 Jun 27;61(7):e02223-16.