2型糖尿病治療薬テネリグリプチンの創製：新規DPP-4阻害剤の創薬研究と結合様式

抄録

Dipeptidyl peptidase IV (DPP-4) inhibitors have built trust through both efficacy and safety in the treatment of type 2 diabetes and have increased the prescription both in Japan and overseas. Among them, teneligliptin has potent and selective DPP-4 inhibitory activity, has an elimination half-life of 24.2 h in human plasma, and is eliminated via excretion from the kidney and metabolism involving some metabolizing enzymes. Therefore, teneligliptin provides postprandial blood glucose-lowering effects that are sustained throughout the day by once-daily treatment and has unnecessary dosage regulation in patients with renal impairment. In this article, discovery and preferable profiles of a novel DPP-4 inhibitor, teneligliptin, discovered first in Japan, are described. By comparative studies of the binding modes of launched DPP-4 inhibitors in the active site, the unique binding mode of teneligliptin in DPP-4 has been revealed.