Inhibitors of Dipeptidyl Peptidase IV - Recent Advances and Structural Views

Title: Inhibitors of Dipeptidyl Peptidase IV - Recent Advances and Structural Views

Volume: 5 Issue: 16

Author(s): Daniel Hunziker, Michael Hennig and Jens-Uwe Peters

Affiliation:

Keywords: hypoglycemia, GLP-1, peptidomimetics, Cyanopyrrolidines, cyclization, monotherapy

Abstract: Prevalence of type 2 diabetes has increased dramatically in the last decades. Current medicines are not yet capable to efficiently prevent or reverse progression of the disease and its associated comorbidities. As a consequence, there is a great need for novel antidiabetic drugs. Treatments of type 2 diabetes that are based on enhanced and sustained action of insulinotropic incretin hormones such as GLP-1 have received much attention in the past years. Treatment strategies include administration of: 1) GLP-1 analogues that are resistant to degradation by the serine protease DPP-IV, and 2) small molecule DPP-IV inhibitors that are able to provide sustained action of endogenous GLP-1, again by preventing its degradation. This review summarizes recent research results for the second approach. It briefly touches upon the advantages that treatment of type 2 diabetes with DPP-IV inhibitors may offer over current medications. In the main section, several important structural classes of DPP-IV inhibitors are described and compared based on literature data. Specific attention is given to the analysis of several X-ray structures of enzyme-inhibitor co-crystals. Finally, as clinical data are steadily emerging for some of the most advanced development candidates, the last section of this review is providing a brief overview of some efficacy data from recent clinical studies with DPP-IV inhibitors.

Cite this article as:

Hunziker Daniel, Hennig Michael and Peters Jens-Uwe, Inhibitors of Dipeptidyl Peptidase IV - Recent Advances and Structural Views, Current Topics in Medicinal Chemistry 2005; 5 (16) . https://dx.doi.org/10.2174/156802605775009685