1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETeneligliptin hydrobromideCat. No.: HY-14806ACAS No.: 906093-29-6Synonyms: MP-513 (hydrobromide)分式: CH.NOSBr.分量: 628.86作靶點(diǎn): Dipeptidyl Peptidase作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 mo

2、nths-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) H2O : 200 mg/mL (318.04 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.5902 mL 7.9509 mL 15.9018 mL5 mM 0.3180 mL 1.5902 mL 3.1804 mL10 mM 0.1590 mL 0.7951 mL 1.5902 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL AC

3、TIVITY物活性 Teneligliptin hydrobromide (MP-513 hydrobromide)種抗壓劑，為 2 腎上腺素能受體 (2AR) 阻滯劑，具有抗氧化、 除由基的活性 1。IC50 & Target IC50: 1 nM (DPP4) 11/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE體外研究 Teneligliptin (MP-513) inhibits all these DPP-4 enzymes in a concentration-dependent manner. The IC50s ofTenelig

4、liptin for rhDPP-4, human plasma, and rat plasma are 0.889, 1.75, and 1.35 nM, respectively. A studyof enzyme inhibition kinetics is conducted for Teneligliptin (MP-513) using Gly-Pro-MCA as the substrate andrhDPP-4 as the enzyme source. Plots based on the Michaelis-Menten equation reveals that Tene

5、ligliptin(MP-513) inhibits DPP-4 in a substrate-competitivemanner; the residual sum of squares for competitive andnon-competitive models is 0.162 and 0.192, respectively. Ki, Km, and Vmax values are 0.406 nM, 24 M,and 6.06 nmol/min, respectively. Teneligliptin (MP-513) inhibits the degradation of GL

6、P-1(7-36)amide with anIC50 of 2.92 nM 1.體內(nèi)研究 Oral administration of Teneligliptin (MP-513) in Wistar rats results in the inhibition of plasma DPP-4 with anED50 of 0.41 mg/kg. Plasma DPP-4 inhibition is sustained even at 24 h after administration of Teneligliptin(MP-513). An oral carbohydrate-loading

7、 test in Zucker fatty rats shows that Teneligliptin (MP-513) at 0.1mg/kg increases the maximum increase in plasmaglucagon-like peptide-1 and insulin levels, and reducesglucose excursions. This effect is observed over 12 h after a dose of 1 mg/kg. An oral fat-loading test inZucker fatty rats also sho

8、ws that Teneligliptin (MP-513) at 1 mg/kg reduces triglyceride and free fatty acidexcursions. In Zucker fatty rats, repeated administration of Teneligliptin (MP-513) for two weeks reducesglucose excursions in the oral carbohydrate-loading test and decreased the plasma levels of triglycerides andfree

9、 fatty acids under non-fasting conditions. Oral administration of Teneligliptin (MP-513) inhibits plasmaDPP-4 in rats in a dose-dependent manner. The ED50 value for Teneligliptin (MP-513) is calculated to be0.41 mg/kg, while those for Sitagliptin and Vildagliptin, 27.3 and 12.8 mg/kg, respectively 1

10、. Teneligliptin(MP-513) improves the histopathological appearance of the liver and decreases intrahepatic triglyceridelevels in an NAFLD model mouse, which is associated with downregulation of hepatic lipogenesis-relatedgenes due to AMPK activation 2.PROTOCOLAnimal Rats 1Administration 12 Nine-week-

11、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 grou

12、ps (0.1, 1, 10and 100 mg/kg). Vehicle (0.5% hydroxypropyl methylcellulose) is orally administered to one group. Bloodsamples 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 4C.

13、 Separated plasma is used for themeasurement of DPP-4 activity. For dose-response curve using the maximum effect in each dose, the doseof the inhibitors which produce half of the maximum effect; ED50 are calculated.Mice 2Monosodium glutamate (MSG) is administered into the neonatal ICR mice at birth

14、as a single-dosesubcutaneous injection (4 mg/g body weight). Among these mice, males are divided into two groups at 4weeks 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/k

15、g per day) in thedrinking water from 4 weeks of age. The treatment dose of Teneligliptin (MP-513) is determined according tothe data from the animal experiments in the drug development process. Although the dose is relatively higherthan that for humans in clinical practice, no notable adverse effect

16、 is observed in the treatment with the dose2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEfor the experimental animal in the process. Both groups are fed HFD from 4-14 weeks of age. At thetermination of the experiment (14 weeks of age), all animals are sacrificed by CO2 asphyxiation to analyzehepa

17、tic histopathology.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Nephrol Dial Transplant. 2019 Jan 8.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Fukuda-Tsuru S, et al. A novel, potent, and long-lasting dipeptidyl

18、peptidase-4 inhibitor, teneligliptin, improves postprandialhyperglycemia and dyslipidemia after single and repeated administrations. Eur J Pharmacol. 2012 Dec 5;696(1-3):194-202.2. Ideta T, et al. The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Attenuates Hepatic Lipogenesis via AMPK Activation in Non-AlcoholicF