Telmisartan-BIBR-277-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemETelmisartanCat. No.: HY-13955CAS No.: 144701-48-4Synonyms: BIBR 277分式: CHNO分量: 514.62作靶點(diǎn): Angiotensin Receptor; Autophagy作通路: GPCR/G Protein; Autophagy儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外

2、實(shí)驗(yàn) DMSO : 6.67 mg/mL (12.96 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 0.67 mg/mL (1.30 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 0.67 mg/mL (1.30 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Telmisarta

3、n種有效的管緊張素II 1型受體 (angiotensin II type 1 receptor) 拮抗劑，能夠抑制其活性，IC50 值為 9.2 nM。IC50 & Target IC50: 9.2 nM (angiotensin II type 1 receptor) 1體外研究 In intact RVSMC cells and in membrane preparations, telmisartan inhibits the binding of 125I-AngII to AT1receptors in a concentration-dependent manner, with

4、an IC50 of 9.2 0.8 nM. In the same experimentalconditions, angiotensin II displaces 125I-AngII with an IC50 value of 2.9 0.5 nM. The specific binding of3Htelmisartan to SMC membranes is displaced by unlabeled telmisartan with an IC50 of 7.7 1.8 nM andby cold AngII with an IC50 of 32.7 5.7 nM 1. Telm

5、isartan treatment (100 M) reduces the proliferation ofthree EAC cell lines (OE19, OE33, and SKGT-4), induces cell cycle arrest in G0/G1 phase and regulates cellcycle-related proteins in EAC cells, and induces the phosphorylation of AMPK and regulates cell cycle-related proteins via the AMPK/mTOR pat

6、hway in EAC cells. Telmisartan inhibits the activation of RTKs,downstream effectors and cell cycle-related proteins 5.體內(nèi)研究 In the telmisartan (0.1, 0.3, and 1 mg/kg)-treated rats, the specific binding of 3Htelmisartan to the surface ofliving RVSMC is saturable and increases quickly to reach equilibr

7、ium within 1 h. Telmisartan dissociates veryslowly from the receptor with a dissociation half-life (t1/2) of 75 min, which is comparable with candesartanand almost 5 times slower than angiotensin II (AngII). In vivo, telmisartan blunts the blood pressure responseto exogenous AngII dose dependently 1

8、. Telmisartan (10 mg/kg/d) administration effectively suppressesaneurysm pathogenesis after PPE infusion as well, regardless of whether treatment is initiated before or afteraneurysm creation or continues for a limited or extended time. Telmisartan treatment is associated withreduced messenger RNA l

9、evels for CCL5 and matrix metalloproteinases 2 and 9 in aneurysmal aortae, withno apparent effect on PPAR-regulated gene expression 2. Telmisartan (1 mg/kg/day) significantlyameliorates neuronal loss and the spatial acquisition impairment in 5XFAD mice, but without any changes ofNeuN expression in t

10、he hippocampus layer. Telmisartan (1 mg/kg/day) treatment reduces amyloid burdenand microglial accumulation in 5XFAD mice brain, induces microglial polarization towards neuroprotectivephenotype, but does not alter the expression levels of NEP and IDE in 5XFAD mice specific brain areas 3.Telmisartan

11、(0.05, 0.1, 1 mg/kg, p.o.) shows significant reduction in immobility time, antagonizes depressionand anxiety, and also significantly attenuates serum cortisol, NO, IL-6 and IL-1 in rats 4. Telmisartan (50 g, i.p.) leads to a 73.2% reduction in tumor growth in mice bearing xenografts derived from OE1

12、9 cells.Furthermore, miRNA expression is significantly altered by telmisartan in vivo 5.PROTOCOLCell Assay 5 Cell proliferation is assayed using the CCK-8 cell counting kit. Briefly, 5103 cells are seeded into each wellof a 96-well plate and cultured in 100 L of RPMI-1640 supplemented with 10% FBS.

13、After 24 h, ARBs(telmisartan, irbesartan, losartan, and valsartan at 0, 1, 10, or 100 M) or vehicle is added to each well, andcells are cultured for an additional 48 h. CCK-8 reagent (10 L) is added to each well, and the plates areincubated at 37C for 3 h. The absorbance is measured at 450 nm using

14、a microplate reader.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Male athymic mice (BALB/c-nu/nu; 6 weeks old; 20-25 g) are maintained under specific pathogen-freeAdministration 5 conditions usi

15、ng a laminar airflow rack. The mice have continuous free access to sterilized (-irradiated) foodand autoclaved water. Each mouse is subcutaneously inoculated with OE19 cells (5106 cells per animal) inthe flank. One week later, the xenografts are identifiable as masses with a maximal diameter 4 mm. T

16、heanimals are randomly assigned to treatment with telmisartan (50 g per day) or diluent only (control). Thetelmisartan group is intraperitoneally (i.p.) injected five times per week with 2 mg/kg telmisartan for fourweeks; the control group is administered 5% DMSO alone for four weeks. Tumor growth i

17、s monitored daily bythe same investigators, and tumor size is measured weekly. The tumor volume (mm3) is calculated as thetumor length (mm) tumor width (mm)2/2. All animals are sacrificed on day 22 after treatment, and allanimals survive during this period. Between-group differences in tumor growth

18、are analyzed by two-wayANOVA.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) Oxid Med Cell Longev. 2019 Mar. Biosci Rep. 2018 Dec 14;38(6). pii: BSR20181501. Oncol Lett. 2018 Apr;15(4):5859-5864. Open Life Sci. 2018 Jul;13(1):242-249.See mor

19、e customer validations on HYPERLINK / www.MedChemEREFERENCES1. Maillard MP, et al. In vitro and in vivo characterization of the activity of telmisartan: an insurmountable angiotensin II receptor antagonist.J Pharmacol Exp Ther. 2002 Sep;302(3):1089-95.2. Xuan H, et al. Inhibition or deletion of angiotensin II type 1 receptor suppresses elastase-induced experimental abdominal aorticaneurysms. J Vasc Surg. 2017 Apr 20. pii: S0741-5214(17)30100-3.3. Torika N, et al. Intranasal telmisartan ameliorates b