Anagliptin-SK-0403-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAnagliptinCat. No.: HY-14877CAS No.: 739366-20-2Synonyms: SK-0403分式: CHNO分量: 383.45作靶点: Dipeptidyl Peptidase作通路: Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 36

2、mg/mL (93.88 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.6079 mL 13.0395 mL 26.0790 mL5 mM 0.5216 mL 2.6079 mL 5.2158 mL10 mM 0.2608 mL 1.3040 mL 2.6079 mL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，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Anagliptin种选择性的，有效的肽酰肽酶 4

3、(DPP-4) 抑制剂，IC50 值为 3.8 nM，对 DPP-8/9 的选择性相对较弱，IC50 值分别为 68 和 60 nM。IC50 & Target IC50: 3.8 nM (DPP-4), 68 nM (DPP-8), 60 nM (DPP-9) 11/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体外研究 Anagliptin is a highly selective, potent inhibitor of DPP-IV, with an IC50 of 3.8 nM, and less selective at DPP-8

4、/9 (68, 60 nM, respectively). Anagliptin does not affect CYP3A4, CYP2C19, CYP2C9, CYP1A2, andCYP2D6 (IC50 10 M) or CYP3A4, CYP2C8, CYP2C9, and CYP1A2 at 50 M. Anagliptin hydrochloridedoes not bind to the hERG channel (E-4031, 90% inhibition at 0.1 M, IC50 500 M in patch clamp usingHEK 293 cells) 1.

5、Anagliptin (1-100 M) dose-dependently suppresses-DPP-4-induced smooth muscle cells(SMCs) proliferation, and reduces TNF- production in cultured monocytes 2.体内研究 Anagliptin (0.3%) alters the quantity and quality of atherosclerotic lesions in apoE-deficient mice, andreduces DPP-4 activity in the plasm

6、a, and total cholesterol level, especially VLDL and LDL-C in mice.Anagliptin also decreases -SMA-positive area and TNF-positive lesions in plaque area of apoE-deficientmice. In addition, Anagliptin does not increase the number of circulating endothelial progenitor cells (EPCs)in apoE-deficient mice

7、2. Anagliptin (0.3%) decreases the low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol, and also reduces the sterol regulatory element-binding protein-2 messengerribonucleic acid expression level in mice 3.PROTOCOLCell Assay 2 To evaluate the growth response of cultured

8、smooth muscle cells (SMCs) to s-DPP-4, thebromodeoxyuridine (BrdU) incorporation assay is performed using cell proliferation ELISA kit. Briefly, SMCsare plated at a density of 3000 cells/well in 96-well culture plates with complete media. At 60%-70%confluence, the SMCs are pretreated with or without

9、 1, 10 or 100 M Anagliptin for 10 minutes and finallystimulated with soluble recombinant human (rh) DPP-4 (5 to 500 ng/mL) for 20 hours. Then, BrdU solution(10 M) is added to the cells and the cells are cultured for another 4 hours. Then, the cells are dried andfixed, and the cellular DNA is denatur

10、ed with FixDenat solution for 30 minutes at room temperature. A ratanti-BrdU monoclonal antibody conjugated with peroxidase is added to the culture plates and incubatedagain at room temperature for 90 minutes. Finally, tetramethylbenzidine is added before incubation for 15minutes at room temperature

11、. Absorbance is measured by a microplate reader at 370 nm 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 Male apoliporotein E (apoE)-deficient mice and C57BL/6 mice at the age of 7 weeks, are housed in specificpathogen-f

12、ree barrier facilities. Mice are maintained under 12-hour light/dark cycle, and fed a standard rodentdiet (22.6% protein, 53.8% carbohydrate, 5.6% fat, 6.6% mineral and vitamin mixture, and 3.3% fiber; total,356 kcal/100 g) with water ad libitum. At the age of 9 weeks, apoE-deficient mice are fed An

13、agliptin-containing diet (0.3%, Anagliptin group, n = 30) or DPP-4 inhibitor-free diet (control group n = 30) for 16weeks 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Biochem Pharmacol. 2018 Oct;156:312-321. Mol Med Rep. 2017 Dec;16(6):

14、8003-8010.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemESee more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Kato N, et al. Discovery and pharmacological characterization of N-2-(2-(2S)-2-cyanopyrrolidin-1-yl-2-oxoethylamino)-2-methylpropyl-2-methylpyrazolo1,5-apyrimidine-6-carbo

15、xamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective DPP-IV inhibitor. Bioorg Med Chem. 2011 Dec 1;19(23):7221-7.2. Ervinna N, et al. Anagliptin, a DPP-4 inhibitor, suppresses proliferation of vascular smooth muscles and monocyte inflammatory reactionand attenuates atherosclerosis in male apo E-deficient mice. Endocrinology. 2013 Mar;154(3):1260-70.3. Yano W, et al. Mechanism of lipid-lowering action of the dipeptidyl peptidase-4 inhibitor, anagliptin, in low-density lipoprotein receptor-deficient mice. J Diab