Tasimelteon

"目录号: HY-14806

Teneligliptin 是一种有效的DPP-4抑制剂，竞争性抑制人血浆，大鼠血浆和人重组DPP-4，IC50约为 1 nM。

生物活性

Description

Teneligliptin is a potent chemotype prolylthiazolidine-basedDPP-4inhibitor, which competitively inhibits human plasma, rat plasma, and human recombinant DPP-4 in vitro, withIC50s of approximately 1 nM.

IC50& Target

IC50: 1 nM (DPP4)[1]

In Vitro

Teneligliptin inhibits all these DPP-4 enzymes in a concentration-dependent manner. The IC50s of Teneligliptin for rhDPP-4, human plasma, and rat plasma are 0.889, 1.75, and 1.35 nM, respectively. A study of enzyme inhibition kinetics is conducted for Teneligliptin using Gly-Pro-MCA as the substrate and rhDPP-4 as the enzyme source. Plots based on the Michaelis-Menten equation reveals that Teneligliptin inhibits DPP-4 in a substrate-competitivemanner; the residual sum of squares for competitive and non-competitive models is 0.162 and 0.192, respectively. Ki, Km, and Vmaxvalues are 0.406 nM, 24 μM, and 6.06 nmol/min, respectively. Teneligliptin inhibits the degradation of GLP-1(7-36)amide with an IC50of 2.92 nM[1].

In Vivo

Oral administration of Teneligliptin in Wistar rats results in the inhibition of plasma DPP-4 with an ED50of 0.41 mg/kg. Plasma DPP-4 inhibition is sustained even at 24 h after administration of Teneligliptin. An oral carbohydrate-loading test in Zucker fatty rats shows that Teneligliptin at ≥0.1 mg/kg increases the maximum increase in plasmaglucagon-like peptide-1 and insulin levels, and reduces glucose excursions. This effect is observed over 12 h after a dose of 1 mg/kg. An oral fat-loading test in Zucker fatty rats also shows that Teneligliptin at 1 mg/kg reduces triglyceride and free fatty acid excursions. In Zucker fatty rats, repeated administration of Teneligliptin for two weeks reduces glucose excursions in the oral carbohydrate-loading test and decreased the plasma levels of triglycerides and free fatty acids under non-fasting conditions. Oral administration of Teneligliptin inhibits plasma DPP-4 in rats in a dose-dependent manner. The ED50value for Teneligliptin is calculated to be 0.41 mg/kg, while those for Sitagliptin and Vildagliptin, 27.3 and 12.8 mg/kg, respectively[1].Teneligliptin improves the histopathological appearance of the liver and decreases intrahepatic triglyceride levels in an NAFLD model mouse, which is associated with downregulation of hepatic lipogenesis-related genes due to AMPK activation[2].

Clinical Trial

NCT02354222

Mitsubishi Tanabe Pharma Corporation

Type 2 Diabetes Mellitus

January 2015

Phase 3

NCT03011177

Handok Pharmaceuticals Co., Ltd.

Type2 Diabetes Mellitus

January 2017

Phase 4

NCT02449330