Teneligliptin (MP-513) is a novel dipeptidyl peptidase 4 (DPP IV) inhibitor for the treatment of type 2 diabetes mellitus with hypoglycemic activity for the study of obesity and diabetes.

DPP4 (human plasma):1.75 nM, DPP4 (human recombinant):6.06 nmol/min (Vmax), DPP4 (human recombinant):0.406 nM (Ki), DPP4 (human recombinant):24 μM (Km), DPP4 (human recombinant):0.889 nM, GLP-1(7-36) amide:2.92 nM, DPP4 (rat plasma):1.35 nM

Teneligliptin 以浓度依赖的方式抑制DPP-4 酶。 Teneligliptin 对 人重组DPP-4、人类血浆和大鼠血浆的 IC50 值分别为 0.889 nM、1.75 nM 和 1.35 nM。使用 Gly-Pro-MCA 作为底物，rhDPP-4 作为酶源，进行了 Teneligliptin 的酶抑制动力学研究，Ki、Km 和 Vmax 值分别为 0.406 nM、24 μM 和 6.06 nmol/min。Teneligliptin 抑制 GLP-1(7-36)amide 的降解具有 IC50 值为 2.92 nM。[1]

在 Wistar 大鼠中，口服 Teneligliptin 可有效抑制血浆 DPP-4，其 ED50 值为 0.41 mg/kg，且这种抑制效果在给药后 24 小时内仍然持续。
在 Zucker 胖鼠的口服脂肪负荷实验中，1 mg/kg 剂量的 Teneligliptin 能够显著降低甘油三酯和游离脂肪酸的波动。连续两周口服 Teneligliptin 的 Zucker 胖鼠在口服糖负荷测试中表现出血糖波动的减少，同时在非禁食状态下，血浆甘油三酯和游离脂肪酸水平也有所降低。[1]
此外，Teneligliptin 还改善了非酒精性脂肪性肝病模型小鼠的肝脏组织病理特征，并降低了肝内甘油三酯水平，这与 AMPK 激活引起的肝脏脂质合成相关基因下调有关。[2]

DPP-4 inhibition assay is carried out using either 5 ng purified recombinant human DPP-4 (rhDPP-4), human plasma (20-fold diluted with assay buffer; phosphate-buffered saline (PBS) containing 0.003% Brij-35 solution), or rat plasma (10-fold diluted with assay buffer) Gly-Pro-MCA as a chromogenic substrate as described previously with slight modifications. DPP-4 inhibitors (Teneligliptin, Sitagliptin, and Vildagliptin) are diluted with assay buffer at several concentrations. Twenty microliters of inhibitor solution, 20 μL of the enzyme source, and 20 μL of Gly-Pro-MCA (final concentration, 25 μM) are mixed with 140 μL or 160 μL of assay buffer to initiate the enzyme reaction. After 20 min (rhDPP-4) or 1 h (plasma) at 37°C, the fluorescence intensity of 7-amino-4-methyl-coumarin (AMC) generated from Gly-Pro-MCA is measured using an automated microplate reader at 360 nm excitation and 465 nm emission. The fluorescence intensity of AMC corresponded to DPP-4 activity[1].