A DPP-4 inhibitor
Teneligliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor (IC50s = 0.37 and 0.29 nM for the human and rat enzymes, respectively).1 It is selective for DPP-4 over DPP-8 and DPP-9 (IC50s = 260 and 540 nM, respectively, for the human enzymes). Teneligliptin (0.03-1 mg/kg) inhibits increases in plasma glucose levels in an oral glucose tolerance test in Zucker fatty rats. It reduces body weight, inhibits hepatic steatosis, and decreases plasma insulin levels in a mouse model of high-fat diet-induced obesity when administered at doses of 30 and 60 mg/kg.2 Teneligliptin scavenges hydroxyl radicals in a cell-free assay (IC50 = 0.315 mM) and decreases urinary levels of 8-hydroxy-2′-deoxyguanosine , a marker of oxidative stress, in a DPP-4-deficient rat model of diabetes induced by streptozotocin when administered at a dose of 10 mg/kg per day.3
1.Yoshida, T., Akahoshi, F., Sakashita, H., et al.Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): A highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetesBioorg. Med. Chem.20(19)5705-5719(2012) 2.Fukuda-Tsuru, S., Kakimoto, T., Utsumi, H., et al.The novel dipeptidyl peptidase-4 inhibitor teneligliptin prevents high-fat diet-induced obesity accompanied with increased energy expenditure in miceEur. J. Pharmacol.723207-215(2014) 3.Kimura, S., Inoguchi, T., Yamasaki, T., et al.A novel DPP-4 inhibitor teneligliptin scavenges hydroxyl radicals: In vitro study evaluated by electron spin resonance spectroscopy and in vivo study using DPP-4 deficient ratsMetabolism65(3)138-145(2016)
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