Immunomodulatory activity of dipeptidyl peptidase‐4 inhibitors in immune‐related diseases

Abstract

Dipeptidyl peptidase‐4 (DPP‐4), also known as CD26, is a 110‐kDa cell surface glycoprotein with enzymatic and signal transducing activity. DPP‐4/CD26 is expressed by a variety of various cells, including CD4+ and CD8+ T cells, B cells, dendritic cells, macrophages, and NK cells. DPP‐4 inhibitors (DPP‐4i) were introduced to clinics in 2006 as new oral antihyperglycemic drugs approved for type 2 diabetes mellitus treatment. In addition to glucose‐lowering effects, emerging data, from clinical studies and their animal models, suggest that DPP‐4i could display anti‐inflammatory and immunomodulatory effects as well, but the molecular and immunological mechanisms of these actions are insufficiently investigated. This review focuses on the modulatory activity of DPP‐4i in the immune system and the possible application of DPP‐4i in other immune‐related diseases in patients with or without diabetes.This article is protected by copyright. All rights reserved

Total Synthesis and Bioactivity Profile of (+)-Ieodomycins A and B and their Stereoisomers

“…Compounds 1 , 2 , and 30b – 30d were evaluated for their antimicrobial, anticancer, antidiabetic, antihypertensive, anti-inflammatory, antioxidant, whitening, moisturizing, and antiwrinkle effects ( Figure 3 ; see the SI for details). In vitro evaluation of type 2 diabetes-linked enzymes including α-amylase ( Figure 4 a), 25 DPP4 (dipeptidyl peptidase-4) ( Figure 4 b), 26 and α-glucosidase 27 identified compounds 30b and 30c , diastereoisomers of (+)-ieodomycin B ( 2 ), as inhibitors, specifically for α-glucosidase ( Figure 4 c). Notably, 3- epi -ieodomycin B ( 30b ) exhibited a superior inhibitory effect (IC 50 = 66.1 μM) against α-glucosidase than did acarbose (IC 50 = 80.0 μM), a positive control ( Figure 4 d).…”