Teneligliptin hydrobromide
(Synonyms: 氢溴酸替格列汀,MP-513 hydrobromide) 目录号 : GC15576
A DPP-4 inhibitor
Cas No.:906093-29-6
Sample solution is provided at 25 µL, 10mM.
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Teneligliptin hydrobromide is a novel, potent, and long-lasting dipeptidyl peptidase-4 (DPP-4) inhibitor with antioxidant properties; competitively inhibited human plasma, rat plasma, and human recombinant DPP-4 in vitro, with IC50 values of about 1 nM[1].
DPP4 is also known as adenosine deaminase complexing protein 2 or CD26. DPP4 is an antigenic enzyme expressed on the membrane of most cell types and is associated with immune regulation, signal transduction and apoptosis [2].
In vitro: In human umbilical vein endothelial cells, Teneligliptin promoted the antioxidant response, reduced ROS levels and induced Nrf2-target genes messenger ribonucleic acid expression. Teneligliptin improved proliferation rates in HUVECs exposed to high glucose, regulating the expression of cell-cycle inhibitors markers (P21, P53 and P27), and reducing proapoptotic genes (BAX and CASP3), while promoteed BCL2 expression. Teneligliptin ameliorated high glucose-induced endoplasmic reticulum stress. Teneligliptin exihibited antioxidant properties and overcome the metabolic memory effect induced by chronic exposure to high glucose in HUVECs[3].
In vivo:In teneligliptin-treated mice, serum alanine aminotransferase and intrahepatic triglyceride levels were significantly decreased (p < 0.05). Teneligliptin also significantly downregulated hepatic mRNA levels of the genes involved in de novo lipogenesis (p < 0.05). Moreover, The hepatic expression levels of phosphorylated AMP-activated protein kinase (AMPK) protein were upregulated by teneligliptin[4]. Orally administration of teneligliptin at a dosage of 20 mg once daily in adults in the ovariectomized (OVX) mice maintained on a high-fat diet, teneligliptin effectively ameliorated the characteristics of metabolic abnormalities associated with postmenopausal obesity. Teneligliptin ameliorated the decreased energy consumption in the dark and light phases, reduced locomotor activity in the dark phase, and lowered core body temperature in OVX-HF[5].
References:
[1] Kishimoto M. Teneligliptin: a DPP-4 inhibitor for the treatment of type 2 diabetes[J]. Diabetes, metabolic syndrome and obesity: targets and therapy, 2013, 6: 187.
[2] Kameoka J, Tanaka T, Nojima Y, et al. Direct association of adenosine deaminase with a T cell activation antigen, CD26[J]. Science, 1993, 261(5120): 466-469.
[3] Pujadas G, De Nigris V, Prattichizzo F, et al. The dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin functions as antioxidant on human endothelial cells exposed to chronic hyperglycemia and metabolic high-glucose memory[J]. Endocrine, 2016: 1-12.
[4] Ideta T, Shirakami Y, Miyazaki T, et al. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-Alcoholic Fatty Liver Disease Model Mice[J]. International journal of molecular sciences, 2015, 16(12): 29207-29218.
[5] Sameshima A, Wada T, Ito T, et al. Teneligliptin improves metabolic abnormalities in a mouse model of postmenopausal obesity[J]. Journal of Endocrinology, 2015, 227(1): 25-36.
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Animal experiment: |
Rats[1] Nine-week-old Wistar rats are randomly divided into 13 groups of eight animals each based on body weight (306.2-374.2 g) and plasma DPP-4 activity. Teneligliptin (MP-513) is orally administered to four groups (0.01, 0.1, 1 and 10 mg/2 mL/kg). Sitagliptin and vildagliptin is orally administered to each four groups (0.1, 1, 10 and 100 mg/kg). Vehicle (0.5% hydroxypropyl methylcellulose) is orally administered to one group. Blood samples are collected from the tail vein with heparinized capillary tubes at 0 h (pre dose) and 0.5, 1, 2, 3, 6, 9, 12, and 24 h (post dose) and centrifuged at 1800 g for 15 min at 4°C. Separated plasma is used for the measurement of DPP-4 activity. For dose-response curve using the maximum effect in each dose, the dose of the inhibitors which produce half of the maximum effect; ED50 are calculated. Mice[2] Monosodium glutamate (MSG) is administered into the neonatal ICR mice at birth as a single-dose subcutaneous injection (4 mg/g body weight). Among these mice, males are divided into two groups at 4 weeks of age: the MSG/HFD group (n=6, Group 1) and the MSG/HFD/Teneligliptin (MP-513)-treated group (n=6, Group 2). The mice in Group 2 are administered Teneligliptin (MP-513) (30 mg/kg per day) in the drinking water from 4 weeks of age. The treatment dose of Teneligliptin (MP-513) is determined according to the data from the animal experiments in the drug development process. Although the dose is relatively higher than that for humans in clinical practice, no notable adverse effect is observed in the treatment with the dose for the experimental animal in the process. Both groups are fed HFD from 4-14 weeks of age. At the termination of the experiment (14 weeks of age), all animals are sacrificed by CO2 asphyxiation to analyze hepatic histopathology. |
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References: [1]. Fukuda-Tsuru S, et al. 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. |
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| Cas No. | 906093-29-6 | SDF | |
| 别名 | 氢溴酸替格列汀,MP-513 hydrobromide | ||
| 化学名 | [(2S,4S)-4-[4-(5-methyl-2-phenylpyrazol-3-yl)piperazin-1-yl]pyrrolidin-2-yl]-(1,3-thiazolidin-3-yl)methanone;pentahydrobromide | ||
| Canonical SMILES | CC1=NN(C(=C1)N2CCN(CC2)C3CC(NC3)C(=O)N4CCSC4)C5=CC=CC=C5.CC1=NN(C(=C1)N2CCN(CC2)C3CC(NC3)C(=O)N4CCSC4)C5=CC=CC=C5.Br.Br.Br.Br.Br | ||
| 分子式 | C22H30N6OS.5/2BrH | 分子量 | 628.86 |
| 溶解度 | ≥ 62.9 mg/mL in DMSO, ≥ 12.1 mg/mL in EtOH with ultrasonic and warming, ≥ 104.8 mg/mL in Water | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5902 mL | 7.9509 mL | 15.9018 mL |
| 5 mM | 0.318 mL | 1.5902 mL | 3.1804 mL |
| 10 mM | 0.159 mL | 0.7951 mL | 1.5902 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet