Preclinical development of dipeptidyl peptidase IV inhibitor alogliptin: a brief overview

Alogliptin is a pyrimidinedione-based potent and selective inhibitor of DPP IV that was discovered by Syrrx (Takeda San Diego) for the treatment of type 2 diabetes mellitus (T2D). Alogliptin is currently launched in Japan with the results of its clinical trials indicating that it is generally well tolerated and shows relatively fewer adverse side effects than other existing therapies for T2D.

The objective of the present review is to provide an overview of the various stages of preclinical development, for example, design, molecular modeling studies, synthesis and in vitro/in vivo pharmacological evaluation of alogliptin. An extensive literature search was conducted to collect abstracts, publications, patents and presentations from various sources. The authors review the information related to the preclinical development of alogliptin and summarize and present the relevant results.

Alogliptin has shown greater in vitro selectivity for DPP IV over closely related enzymes, including DPP VIII and DPP IX, in comparison with other launched DPP IV inhibitors such as sitagliptin, saxagliptin and vildagliptin. Alogliptin has been evaluated in different diabetic animal models and is found to reduce glycosylated hemoglobin, plasma glucose, glucagon and triglycerides levels. Alogliptin also ameliorates β-cell function, with a significant increase in plasma insulin levels. The authors believe that this potent and selective inhibitor of DPP IV could compete with traditional oral anti-diabetic therapies in the future.