DPP4 (IC50 = 1 nM)

体外活性：在人脐静脉内皮细胞中，Teneligliptin 促进抗氧化反应，降低 ROS 水平并诱导 Nrf2 靶基因信使核糖核酸表达。特力利汀提高了暴露于高葡萄糖的 HUVEC 的增殖率，调节细胞周期抑制剂标记物（P21、P53 和 P27）的表达，并减少促凋亡基因（BAX 和 CASP3），同时促进 BCL2 表达。特力利汀改善高葡萄糖诱导的内质网应激。特力利汀表现出抗氧化特性，并克服了 HUVEC 中因长期暴露于高葡萄糖而引起的代谢记忆效应。细胞测定：接种 HUVEC 并使其附着过夜。第二天，将细胞暴露于含或不含特力利汀（0.1、1.0 或 3.0 µmol/L）或西他列汀（0.5 µmol/L）的三种葡萄糖实验条件之一：连续正常葡萄糖（NG-5 mmol/L）21天;持续高血糖（HG-25 mmol/L）21天；和高代谢记忆（HM-连续 14 天 HG，然后最后 7 天 NG）。 HUVEC 在 3 周内培养，每 48 小时更换一次培养基，且不传代细胞。

特力利汀可减轻绝经后肥胖小鼠模型的体重增加、脂肪积累以及血清胰岛素和甘油三酯水平。还可改善葡萄糖不耐受，但剂量不影响胰岛素敏感性。它可以减轻绝经后肥胖小鼠模型中性腺周围脂肪和肝脏脂肪变性的慢性炎症。特力利汀可增加绝经后肥胖小鼠在黑暗阶段的运动活性并增加能量消耗。研究发现，这种化合物通过激活 AMPK 并下调参与脂肪生成的基因的表达来减弱肝脏中的脂肪生成。

HUVEC 被播种并给予过夜窗口以附着。第二天将细胞置于三种葡萄糖实验条件下，有或没有特力利汀（0.1、1.0 或 3.0 µmol/L）或西格列汀（0.5 µmol/L）：连续正常葡萄糖（NG-5 mmol/L） 21 天；持续高血糖（HG-25 mmol/L）21天；或高代谢记忆（HM-连续 14 天 HG，然后最后 7 天 NG）。在三周的培养期间，HUVEC 进行细胞传代，并且每 48 小时更换一次培养基。

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.

[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.

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

Solid powder

CC1=NN(C(=C1)N2CCN(CC2)[C@H]3C[C@H](NC3)C(=O)N4CCSC4)C5=CC=CC=C5.CC1=NN(C(=C1)N2CCN(CC2)[C@H]3C[C@H](NC3)C(=O)N4CCSC4)C5=CC=CC=C5.Br.Br.Br.Br.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

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.

---

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.

---

View More

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.

---

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.

---

请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。