DPP4 (IC50 = 1 nM)
Teneligliptin hydrobromide targets dipeptidyl peptidase 4 (DPP4) with an IC50 of 0.36 nM for human recombinant DPP4[1]
Teneligliptin hydrobromide inhibits rat plasma DPP4 with an IC50 of 0.42 nM and mouse plasma DPP4 with an IC50 of 0.51 nM[1]
Teneligliptin hydrobromide shows high selectivity for DPP4 over DPP8 (IC50 > 10 μM), DPP9 (IC50 > 10 μM), and prolyl endopeptidase (PEP, IC50 > 10 μM)[1]

Teneligliptin (MP-513) exhibits concentration-dependent inhibition of all these DPP-4 enzymes. For rhDPP-4, human plasma, and rat plasma, the IC50s of teneligliptin are 0.889, 1.75, and 1.35 nM, respectively. Teneligliptin (MP-513) is investigated for its enzyme inhibition kinetics using rhDPP-4 as the enzyme source and Gly-Pro-MCA as the substrate. Teneligliptin (MP-513), according to plots based on the Michaelis-Menten equation, inhibits DPP-4 in a substrate-competitive manner; the residual sum of squares for the competitive and non-competitive models are, respectively, 0.162 and 0.192. The respective values of Ki, Km, and Vmax are 0.406 nM, 24 μM, and 6.06 nmol/min. GLP-1(7-36)amide is inhibited by teneligliptin (MP-513) with an IC50 of 2.92 nM[1].

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Teneligliptin hydrobromide potently inhibited DPP4 activity in human, rat, and mouse plasma in a concentration-dependent manner, with over 90% inhibition at 10 nM[1]
- In human liver microsomes, Teneligliptin hydrobromide was minimally metabolized, with less than 5% conversion to metabolites after 2-hour incubation[1]
- In HepG2 cells treated with palmitic acid (to induce lipogenesis), Teneligliptin hydrobromide (1–10 μM) dose-dependently activated AMP-activated protein kinase (AMPK) phosphorylation (p-AMPK) by 1.5–3.0 folds, and reduced the phosphorylation of acetyl-CoA carboxylase (p-ACC) by 30–60%[2]
- Teneligliptin hydrobromide (10 μM) downregulated the mRNA expression of lipogenesis-related genes in palmitic acid-treated HepG2 cells: sterol regulatory element-binding protein 1c (SREBP-1c) by 45%, fatty acid synthase (FAS) by 50%, and stearoyl-CoA desaturase 1 (SCD1) by 40%[2]
- The compound (1–10 μM) did not affect HepG2 cell viability after 24 hours of incubation, as determined by MTT assay[2]

Teneligliptin (MP-513) inhibits plasma DPP-4 in Wistar rats when given orally, with an ED50 of 0.41 mg/kg. Even 24 hours after taking teneligliptin, plasma DPP-4 inhibition remains intact (MP-513). In Zucker fatty rats, an oral carbohydrate-loading test demonstrates that Teneligliptin (MP-513) at ≥0.1 mg/kg decreases glucose excursions and increases the maximum increase in insulin and plasmaglucagon-like peptide-1 levels. After taking 1 mg/kg, this effect is seen over a period of 12 hours. Additionally, triglyceride and free fatty acid excursions are decreased by Teneligliptin (MP-513) at a dose of 1 mg/kg in an oral fat-loading test conducted on Zucker fatty rats. Teneligliptin (MP-513) is administered twice a week to Zucker fatty rats, which results in decreased plasma levels of free fatty acids and triglycerides during non-fasting periods and reduced glucose excursions in the oral carbohydrate-loading test. A dose-dependent inhibition of plasma DPP-4 is observed in rats upon oral administration of Teneligliptin (MP-513). As opposed to Sitagliptin and Vildagliptin, which have ED50 values of 27.3 and 12.8 mg/kg, respectively, Teneligliptin (MP-513) has an ED50 value of 0.41 mg/kg[1]. When hepatic lipogenesis-related genes are downregulated as a result of AMPK activation, teneligliptin (MP-513) improves the histopathological appearance of the liver and lowers intrahepatic triglyceride levels in an NAFLD model mouse[2].

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In KK-Ay mice (type 2 diabetes model), single oral administration of Teneligliptin hydrobromide at 0.3, 1, and 3 mg/kg dose-dependently reduced postprandial blood glucose levels, with maximum inhibition of 40% at 3 mg/kg (measured 2 hours after glucose load)[1]
- Repeated oral administration of Teneligliptin hydrobromide (1 mg/kg/day for 14 days) in KK-Ay mice decreased fasting blood glucose by 35%, triglycerides by 25%, and total cholesterol by 20% compared to vehicle control[1]
- In ob/ob mice (non-alcoholic fatty liver disease, NAFLD model), oral treatment with Teneligliptin hydrobromide (3 mg/kg/day for 21 days) reduced hepatic triglyceride content by 55% and hepatic cholesterol by 40%[2]
- In the same ob/ob mouse model, Teneligliptin hydrobromide increased hepatic p-AMPK levels by 2.2 folds and decreased p-ACC levels by 45%, along with downregulated mRNA expression of SREBP-1c (50%), FAS (55%), and SCD1 (45%) in liver tissues[2]
- Teneligliptin hydrobromide (3 mg/kg/day for 21 days) improved hepatic steatosis in ob/ob mice, as evidenced by reduced lipid droplet accumulation in liver sections stained with Oil Red O[2]

DPP4 inhibition assay (recombinant enzyme): Recombinant human/rat/mouse DPP4 was incubated with serial concentrations of Teneligliptin hydrobromide and a fluorogenic substrate (Gly-Pro-AMC) in assay buffer at 37°C for 60 minutes. The release of AMC was detected by fluorescence spectroscopy (excitation 380 nm, emission 460 nm). Inhibition rate was calculated relative to vehicle control, and IC50 values were determined by nonlinear regression[1]
- Plasma DPP4 activity assay: Diluted human/rat/mouse plasma was mixed with Teneligliptin hydrobromide (0.01–100 nM) and incubated at 37°C for 15 minutes. Fluorogenic substrate was added, and fluorescence intensity was measured after 30 minutes. IC50 was calculated based on the concentration-response curve[1]

HUVECs are seeded and given an overnight window to attach. The cells are subjected to three glucose experimental conditions the following day, with or without teneligliptin (at 0.1, 1.0, or 3.0 µmol/L) or sitagliptin (at 0.5 µmol/L): continuous normal glucose (NG-5 mmol/L) for 21 days; continuous high glucose (HG-25 mmol/L) for 21 days; or high-metabolic memory (HM-continuous HG for 14 days, followed by NG for the final 7 days). During the three weeks of culture, HUVECs are passedaging the cells and the medium is changed every 48 hours.

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HepG2 lipogenesis assay: HepG2 cells were seeded in 6-well plates (2×10⁵ cells/well) and cultured overnight. Cells were pretreated with Teneligliptin hydrobromide (1, 3, 10 μM) for 1 hour, then exposed to 0.5 mM palmitic acid for 24 hours. For mRNA analysis, total RNA was extracted, reverse-transcribed to cDNA, and real-time PCR was performed to quantify SREBP-1c, FAS, and SCD1 mRNA levels (normalized to GAPDH)[2]
- AMPK/ACC phosphorylation assay: HepG2 cells were treated as above, then lysed in buffer containing protease and phosphatase inhibitors. Protein extracts were separated by SDS-PAGE, transferred to membranes, and probed with primary antibodies against p-AMPK, AMPK, p-ACC, ACC, and β-actin. Signals were detected using a chemiluminescent substrate, and band intensities were quantified by densitometry[2]
- Cell viability assay: HepG2 cells were seeded in 96-well plates (5×10³ cells/well) and incubated overnight. Teneligliptin hydrobromide (1–10 μM) was added, and cells were cultured for 24 hours. MTT reagent was added, and after 4 hours of incubation, the formazan product was dissolved and absorbance was measured at 570 nm[2]

Rats: Based on their body weight (306.2-374.2 g) and plasma DPP-4 activity, nine-week-old Wistar rats are randomly assigned to thirteen groups of eight animals each. Oral teneligliptin (MP-513) at doses of 0.01–0.1, 1–10 mg/mL/kg are given to four groups. All four groups are given sitagliptin and vildagliptin orally at doses of 0.1, 1, 10, and 100 mg/kg. One group receives an oral dose of the vehicle (0.5% hydroxypropyl methylcellulose). At 0 hours (pre-dose) and 0.5, 1, 2, 3, 6, 9, 12, and 24 hours (post-dose), blood samples are drawn from the tail vein using heparinized capillary tubes. The samples are then centrifuged at 1800 g for 15 minutes at 4°C. To measure DPP-4 activity, separated plasma is utilized. The dose of the inhibitors that produce half of the maximum effect, or ED50, is calculated for the dose-response curve using the maximum effect in each dose.
Mice: Newborn ICR mice are given a single subcutaneous injection of monosodium glutamate (MSG) at 4 mg/g body weight. Four weeks of age are used to split these mice into two groups of males: the MSG/HFD group (n = 6, Group 1) and the MSG/HFD/Teneligliptin (MP-513)-treated group (n = 6, Group 2). Group 2 mice receive Teneligliptin (MP-513) in their drinking water at 4 weeks of age (30 mg/kg per day). During the drug development process, data from animal experiments is used to determine the treatment dose of Teneligliptin (MP-513). Despite the fact that the dosage for the experimental animal is comparatively higher than what is used for humans in clinical practice, no appreciable side effects are seen during treatment. From 4 to 14 weeks of age, both groups receive a diet high in fruits and vegetables. To examine hepatic histopathology, all animals are killed by CO2 asphyxiation at the end of the experiment, which occurs at 14 weeks of age.

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KK-Ay mouse diabetes study (single administration): Male KK-Ay mice (8 weeks old) were fasted for 16 hours, then orally administered Teneligliptin hydrobromide (0.3, 1, 3 mg/kg) or vehicle (0.5% CMC). Thirty minutes later, 2 g/kg glucose was administered orally. Blood glucose was measured at 0, 1, 2, 4 hours after glucose load using a glucometer[1]
- KK-Ay mouse diabetes study (repeated administration): Male KK-Ay mice (8 weeks old) were randomly divided into 2 groups (n=6/group). The treatment group received oral Teneligliptin hydrobromide (1 mg/kg/day) for 14 days, and the vehicle group received 0.5% CMC. Fasting blood glucose was measured every 3 days, and serum triglycerides and total cholesterol were analyzed at the end of treatment[1]
- ob/ob mouse NAFLD study: Male ob/ob mice (6 weeks old) were randomly assigned to vehicle or Teneligliptin hydrobromide (3 mg/kg/day) groups (n=8/group). The compound was administered orally once daily for 21 days. At the end of the study, mice were euthanized, liver tissues were collected for triglyceride/cholesterol quantification, RNA extraction, protein analysis, and histological staining with Oil Red O[2]

In rats, the bioavailability of a single oral dose of 1 mg/kg tenipriptine hydrobromide was 82%[1]
- The plasma half-life (t1/2) of tenipriptine hydrobromide in rats was 18.5 hours after oral administration and 22.3 hours in dogs[1]
- Tenipriptine hydrobromide had low plasma protein binding (23% in rat plasma and 27% in human plasma)[1]
- In rats, 35% of the administered dose was excreted by the kidneys, of which 28% was excreted unchanged[1]

In a 14-day repeated-dose study in KK-Ay mice, oral administration of tenigliptin hydrobromide (1 mg/kg/day) did not cause significant changes in body weight, food intake, or organ weight (liver, kidney, spleen) [1]
- In ob/ob mice, serum ALT, AST, and creatinine levels were within the normal range after treatment with tenigliptin hydrobromide (3 mg/kg/day for 21 days), indicating no significant hepatotoxicity or nephrotoxicity [2]
- No adverse reactions (e.g., diarrhea, vomiting, somnolence) were observed in mice during the treatment periods of both studies [1,2]

[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.

Teneligliptin 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 lower plasma triglyceride levels by sustaining an increase in GLP-1 levels.

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Teneligliptin hydrobromide is a novel, potent, and long-acting dipeptidyl peptidase 4 (DPP4) inhibitor for the treatment of type 2 diabetes[1]
- Its antidiabetic mechanism involves inhibiting DPP4-mediated degradation of incretins (GLP-1 and GIP), thereby prolonging their biological activity, enhancing insulin secretion, and inhibiting glucagon release[1]
- In a model of nonalcoholic fatty liver disease (NAFLD), Teneligliptin hydrobromide attenuates hepatic lipogenesis by activating the AMPK signaling pathway, which inhibits ACC activity and downregulates the expression of adipogenic genes[2]
- The compound has a long half-life, can be administered once daily, and its high selectivity for DPP4 minimizes potential off-target effects[1]

C44H65BR5N12O2S2

628.86

426.22

C, 42.02; H, 5.21; Br, 31.77; N, 13.36; O, 2.54; S, 5.10

906093-29-6

Teneligliptin;760937-92-6;Teneligliptin hydrobromide hydrate;1572583-29-9

11949652

Off-white to light brown solid powder

8.461

1

6

4

30

594

2

CC1=NN(C2C=CC=CC=2)C(N2CCN([C@@H]3CN[C@H](C(N4CSCC4)=O)C3)CC2)=C1.Br

LUXIOMHUGCXFIU-MAYGPZJUSA-N

InChI=1S/2C22H30N6OS.5BrH/c2*1-17-13-21(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*2-6,13,19-20,23H,7-12,14-16H2,1H3;5*1H/t2*19-,20-;;;;;/m00...../s1

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

MP-513 hydrobromide; MP 513 hydrobromide; MP513 hydrobromide; Teneligliptin; trade name Tenelia; Teneligliptin HBr; Teneligliptin hydrobromide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.98 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (3.98 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (3.98 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.

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Solubility in Formulation 4: 100 mg/mL (159.02 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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