氯沙坦鉀作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetLosartan potassiumCat. No.: HY-17512ACAS No.: 124750-99-8分式: CHClKNO分量: 461作靶點: Angiotensin Receptor作通路: GPCR/G Protein儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 110 mg/mL (238.61 mM)H2O : 33.33 mg/mL (72.30 mM; Need ultrasonic)* means so

2、luble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 2.1692 mL 10.8460 mL 21.6920 mL5 mM 0.4338 mL 2.1692 mL 4.3384 mL10 mM 0.2169 mL 1.0846 mL 2.1692 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；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 儲存時，請在 6 個內(nèi)使，-20C 儲存時

3、，請在 1 個內(nèi)使。BIOLOGICAL ACTIVITY物活性 Losartan potassium (DuP-753 potassium) ，IC50 為 20 nM。管緊張素 II 受體 1 型 (AT1)拮抗劑，與管緊張素 II 與 AT1 的結(jié)合競爭IC & Target IC50: 20 nM (angiotensin II)體外研究 Losartan competes with the binding of angiotensin II to AT1 receptors. The concentration that inhibits 50% of thebinding of a

4、ngiotensin II (IC50) is 20 nM1. Losartan (40 M) affects ISC but prevents the effect of ANGII on ISC2.Losartan significantly reduces Ang II-mediated cell proliferation in endometrial cancer cells. The combination oflosartan and anti-miR-155 has a significantly greater antiproliferative effect compare

5、d to each drug alone3.Page 1 of 2 www.MedChemE體內(nèi)研究 Losartan (0.6 g/L, p.o.) -treated Fbn1C1039G/+ mice show a reduction in distal airspace caliber relative to placebo-treated Fbn1C1039G/+ animals. The doses of losartan and propranolol are titrated to achieve comparable hemodynamic effects. Analysis

6、of pSmad2 nuclear staining reveals that losartan antagonizes TGF- signaling in theaortic wall of Fbn1C1039G/+ mice. Losartan can improve disease manifestations in the lungs, an event that cannotplausibly relate to improved hemodynamics4. Losartan (10 mg/kg, intraarterial injection) increases blood a

7、ngiotensinlevels four- to sixfold. Losartan (10 mg/kg, i.p.) increases plasma renin levels 100-fold; plasma angiotensinogen levelsdecreases to 24% of control; and plasma aldosterone levels are unchanged5.PROTOCOLCell Assay 3 An MTT assay is used to measure cell proliferation and viability. For the a

8、ssay, 5000 cells in 200 L media per well areseeded in a 96 well plate. After overnight incubation to allow for cell attachment, the medium is removed by suction.MTT at 1 mg/mL concentration in serum-free medium is added and then incubated for 4 h at 37C. After removal ofMTT solution, 100 L of DMSO i

9、s added to dissolve formazan crystals. Absorbance at 570 nm and at 600 nm as areference is then measured using a microplate reader. The difference in absorbance is thus relative to the extent ofcell survival.MCE has not independently confirmed the accuracy of these methods. They are for reference on

10、ly.Animal Female Fbn1C1039G/+ mice undergo timed matings with wild-type male mice. At 14.5d post-coitum, pregnant femaleAdministration 4 Fbn1C1039G/+ mice are treated with oral losartan (0.6 g/L in drinking water; n=10), propranolol (0.5 g/L; n=6) orplacebo (n=12). Therapy is continued throughout la

11、ctation and after weaning until 10 months of age. Mice aresacrificed and examined using the techniques described above. Propranolol is used for comparison with losartanbecause -adrenergic receptor blockade is the current albeit controversial standard of care to modulate abnormalgrowth of the aortic

12、root in MFS. Beginning at 7 weeks of age, wild-type and Fbn1C1039G/+ mice are treated with orallosartan (0.6 g/L in drinking water; n=5), propranolol (0.5 g/L; n=7) or placebo (n=10). Mice are continued on oraltherapy for 6 months and then sacrificed.MCE has not independently confirmed the accuracy

13、of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cell Death Dis. 2020 May 22;11(5):390. FASEB J. 2019 May;33(5):6254-6268. FASEB J. 2018 Sep;32(9):5051-5062. Int J Nanomedicine. 2018 Nov 13;13:7409-7426. Am J Physiol Heart Circ Physiol. 2018 Mar 1;314(3):H580-H592.See more customer validati

14、ons on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Burnier, M. Angiotensin II type 1 receptor blockers. Circulation, 2001. 103(6): p. 904-12.2. Ashry, O., et al. Evidence for expression and function of angiotensin II receptor type 1 in pulmonary epithelial cells. Respir Physiol Neurobiol, 2014.3

15、. Choi, C.H., et al. Angiotensin II type I receptor and miR-155 in endometrial cancers: synergistic antiproliferative effects of anti-miR-155 and losartan onendometrial cancer cells. Gynecol Oncol, 2012. 126(1): p. 124-31.Page 2 of 3 www.MedChemE4. Habashi, J.P., et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science, 2006. 312(5770): p. 117-21.5. Campbell, D.J., et al. Effects of losartan on angiotensin and bradykinin peptides and angiotensin-converting enzyme. J Cardiovasc Pharmacol, 1995.