Teneligliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. [2]

All of these DPP-4 enzymes are inhibited by teneligliptin (MP-513) in a concentration-dependent manner. Teneligliptin (MP-513) has an IC50 of 0.889, 1.75, and 1.35 nM against rhDPP-4, human plasma, and rat plasma, respectively. Teneligliptin (MP-513) was used as the enzyme source and Gly-Pro-MCA as the substrate in an investigation of the kinetics of enzyme inhibition. Teneligliptin (MP-513) inhibits DPP-4 in a substrate-competitive manner, according to plots based on the Michaelis-Menten equation; the residual sums of squares for the competitive and noncompetitive models were 0.162 and 0.192, respectively. The values of Ki, Km, and Vmax are 6.06 nmol/min, 24 μM, and 0.406 nM, respectively. With an IC50 of 2.92 nM, teneligliptin (MP-513) inhibits the breakdown of GLP-1(7-36)amide[1].

---

Teneligliptin competitively inhibited DPP-4 activity in a concentration-dependent manner. IC₅₀ values: 0.889 nmol/L against recombinant human DPP-4; 1.75 nmol/L against human plasma DPP-4; 1.35 nmol/L against rat plasma DPP-4. [1]
Kinetic analysis using recombinant human DPP-4 and the substrate Gly-Pro-MCA revealed that teneligliptin is a competitive inhibitor, with Kᵢ = 0.406 nmol/L, Kₘ = 24.0 μmol/L, and Vₘₐₓ = 6.06 mmol/min. [1]
Teneligliptin inhibited the degradation of GLP-1(7-36)amide in rat plasma, with an IC₅₀ of 2.92 nmol/L. [1]
Comparative in vitro studies showed that teneligliptin (IC₅₀ = 1.01 nmol/L for rhDPP-4, 1.45 nmol/L for human plasma, 1.14 nmol/L for rat plasma) was more potent than sitagliptin (IC₅₀ = 6.74, 4.88, 10.4 nmol/L, respectively) and vildagliptin (IC₅₀ = 10.5, 7.67, 6.81 nmol/L, respectively). [1]

Teneligliptin (MP-513) has an ED50 of 0.41 mg/kg and can inhibit plasma DPP-4 when given orally to Wistar rats. Even 24 hours after the dose of teneligliptin (MP-513) there was still suppression of plasma DPP-4. Teneligliptin (MP-513) at ≥0.1 mg/kg maximally enhanced plasma glucagon-like peptide-1 and insulin levels and decreased blood glucose excursions in Zucker adipose rats, according to an oral carbohydrate loading test. Within 12 hours of ingesting a dose of 1 mg/kg, this effect is seen. Additionally, triglyceride and free fatty acid excursions were decreased by teneligliptin (MP-513) at a dose of 1 mg/kg in an oral fat loading test conducted on Zucker adipose rats. Teneligliptin (MP-513) was administered twice a week for two weeks in Zucker fatty rats. This treatment decreased plasma triglyceride and free fatty acid levels while the animals were not fasting. It also decreased glucose excursions in an oral carbohydrate loading test. Rat plasma DPP-4 is inhibited by oral treatment of Teneligliptin (MP-513) in a dose-dependent manner. Teneligliptin (MP-513) was shown to have an ED50 value of 0.41 mg/kg, whereas sitagliptin and vildagliptin had ED50 values of 27.3 and 12.8 mg/kg, respectively[1]. Teneligliptin (MP-513) is associated with the downregulation of hepatic lipogenesis-related genes brought on by AMPK activation, which enhances the histological appearance of the liver and lowers intrahepatic triglyceride levels in NAFLD model mice [2].

---

In a nonalcoholic fatty liver disease (NAFLD) mouse model (MSG-treated neonatal ICR mice fed a high-fat diet), teneligliptin (30 mg/kg/day in drinking water for 10 weeks) significantly reduced hepatic steatosis and inflammation, as assessed by the NAFLD activity score (NAS). [2]
- Teneligliptin significantly decreased intrahepatic triglyceride levels compared to control mice. [2]
- Teneligliptin significantly increased the ratio of phosphorylated AMPK (p-AMPK) to total AMPK in liver tissue, indicating AMPK activation. [2]
- Teneligliptin significantly decreased the hepatic mRNA expression of lipogenesis-related genes: Acc, Fas, Srebp1c, and Elovl6. [2]
- Serum alanine aminotransferase (ALT) levels were significantly reduced in teneligliptin-treated mice. [2]
- No significant changes were observed in serum free fatty acids (FFA), glucose, insulin, or triglyceride levels between groups. [2]
- Body weight, liver weight, and white adipose tissue weight were not significantly different between control and treated groups. [2]

DPP-4 inhibition assay: DPP-4 inhibitors were diluted with assay buffer at several concentrations. 20 μL of inhibitor solution, 20 μL of enzyme source (recombinant human DPP-4, human plasma diluted 20-fold, or rat plasma diluted 10-fold), and 20 μL of Gly-Pro-MCA (final concentration 25 μmol/L) were mixed with 140 μL (in vitro) or 160 μL (in vivo) of assay buffer to initiate the reaction. After 20 minutes (rhDPP-4) or 1 hour (plasma) at 37°C, the fluorescence intensity of 7-amino-4-methyl-coumarin generated from Gly-Pro-MCA was measured at 360 nm excitation and 465 nm emission. [1]
Kinetics of DPP-4 inhibition: rhDPP-4 activity was measured at several concentrations of teneligliptin and Gly-Pro-MCA. The inhibition pattern was analyzed by nonlinear regression with models as expansions of the Michaelis-Menten equation to competitive or noncompetitive inhibition. Log(Kᵢ), log(Kₘ), and Vₘₐₓ were calculated, and estimates of Kᵢ and Kₘ were calculated by inverse logarithmic transformation. [1]
GLP-1 degradation assay: Teneligliptin was diluted with PBS containing 0.003% Brij-35 solution and 1% bovine serum albumin. 5 μL of teneligliptin solution or vehicle was incubated with 175 μL of diluted rat plasma (final concentration 30%). The reaction was initiated by adding 20 μL of GLP-1 solution (final concentration 150 pmol/L). After 1 hour at 37°C, the concentration of active GLP-1 was measured using an automated microplate reader. [1]

Neonatal ICR mice received a single subcutaneous injection of monosodium glutamate (MSG) at birth (4 mg/g body weight). At 4 weeks of age, male mice were divided into two groups: MSG/high-fat diet (HFD) control group and MSG/HFD/teneligliptin-treated group (n = 6 per group). [2]
- Teneligliptin was administered at 30 mg/kg/day via drinking water from 4 to 14 weeks of age. [2]
- Both groups were fed a high-fat diet (HFD) from 4 to 14 weeks of age. [2]
- At 14 weeks of age, all animals were euthanized by CO₂ asphyxiation. Blood samples were collected from the inferior vena cava after 6 hours of fasting. Liver tissues were harvested for histopathology, lipid analysis, and molecular assays. [2]

---

Neonatal ICR mice received a single subcutaneous injection of monosodium glutamate (MSG) at birth (4 mg/g body weight). At 4 weeks of age, male mice were divided into two groups: MSG/high-fat diet (HFD) control group and MSG/HFD/teneligliptin-treated group (n = 6 per group). [2]
- Teneligliptin was administered at 30 mg/kg/day via drinking water from 4 to 14 weeks of age. [2]
- Both groups were fed a high-fat diet (HFD) from 4 to 14 weeks of age. [2]
- At 14 weeks of age, all animals were euthanized by CO₂ asphyxiation. Blood samples were collected from the inferior vena cava after 6 hours of fasting. Liver tissues were harvested for histopathology, lipid analysis, and molecular assays. [2]

[1]. A novel, potent, and long-lasting dipeptidyl peptidase-4 inhibitor, teneligliptin, improves postprandial hyperglycemia and dyslipidemia after single and repeated administrations. Eur J Pharmacol. 2012 Dec 5;696(1-3):194-202.

[2]. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice. Int J Mol Sci. 2015 Dec 8;16(12):29207-18.

Ticalcliptin is an amino acid amide. It has been investigated for the treatment of type 2 diabetes. Ticalcliptin is a long-acting, orally bioavailable pyrrolidine dipeptidyl peptidase-4 (DPP-4) inhibitor with glycemic activity. Ticalcliptin may also lower plasma triglyceride levels by sustaining an increase in GLP-1 levels.

---

Teneligliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used clinically for type 2 diabetes mellitus. [2]
- This study demonstrates that teneligliptin improves hepatic steatosis and inflammation in a NAFLD mouse model through activation of AMPK and subsequent downregulation of lipogenic genes (Srebp1c, Fas, Acc, Elovl6). [2]
- The NAFLD model used in this study involves neonatal MSG injection combined with high-fat diet, which induces obesity, insulin resistance, and hepatic steatosis. [2]
- The study suggests that DPP-4 inhibitors such as teneligliptin may have therapeutic potential for NAFLD/NASH. [2]

C22H30N6OS

426.58

426.22

760937-92-6

Teneligliptin hydrobromide;906093-29-6;Teneligliptin hydrobromide hydrate;1572583-29-9;Teneligliptin-d8;1391012-95-5;Teneligliptin-d4

11949652

White to off-white solid powder

1.4±0.1 g/cm3

663.4±55.0 °C at 760 mmHg

355.0±31.5 °C

0.0±2.0 mmHg at 25°C

1.721

1.15

1

6

4

30

594

2

O=C([C@H]1NC[C@@H](N2CCN(C3=CC(C)=NN3C4=CC=CC=C4)CC2)C1)N5CSCC5

WGRQANOPCQRCME-PMACEKPBSA-N

InChI=1S/C22H30N6OS/c1-17-13-21(28(24-17)18-5-3-2-4-6-18)26-9-7-25(8-10-26)19-14-20(23-15-19)22(29)27-11-12-30-16-27/h2-6,13,19-20,23H,7-12,14-16H2,1H3/t19-,20-/m0/s1

[(2S,4S)-4-[4-(5-methyl-2-phenylpyrazol-3-yl)piperazin-1-yl]pyrrolidin-2-yl]-(1,3-thiazolidin-3-yl)methanone

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~33.33 mg/mL (~78.13 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (5.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)