氯沙坦作用机制 - Medchemexpress - MCE中国

1、Product Data SheetLosartanCat. No.: HY-17512CAS No.: 114798-26-4分式: CHClNO分量: 422.91作靶点: Angiotensin Receptor作通路: GPCR/G Protein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 : 100 mg/mL (236.46 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10

2、mgConcentration制备储备液1 mM 2.3646 mL 11.8228 mL 23.6457 mL5 mM 0.4729 mL 2.3646 mL 4.7291 mL10 mM 0.2365 mL 1.1823 mL 2.3646 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；旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存式和期限：-80C, 6 months; -20C, 1 month。-80C 储存时，请在 6 个内使，-20C 储存时，请在 1 个内使。体内实验请根据您的实验动物和给药式选择适当的溶解案。以下溶解案都请先按照 In Vitr

3、o 式配制澄清的储备液，再依次添加助溶剂：为保证实验结果的可靠性，澄 的储备液可以根据储存条件，适当保存；体内实验的作液，建议您现现配，当天使； 以下溶剂前显的百分 指该溶剂在您配制终溶液中的体积占；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的式助溶1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.91 mM); Clear solution此案可获得 2.5 mg/mL (5.91 mM，饱和度未知) 的澄清溶液。以 1 mL 作液为例，取 100 L 25.0 mg

4、/mL 的澄 DMSO 储备液加到 400 L PEG300 中，混合均匀；向上述体系中加50 L Tween-80，混合均匀；然后继续加 450 L 理盐定容 1 mL。2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.91 mM); Clear solutionPage 1 of 2 www.MedChemE此案可获得 2.5 mg/mL (5.91 mM，饱和度未知) 的澄 溶液，此案不适于实验周 期在半个以上的实验。以 1 mL 作液为例，取 100 L 25.0 mg/mL 的澄 DMSO 储备液加到 900 L

5、油中，混合均匀。BIOLOGICAL ACTIVITY物活性 Losartan管紧张素II受体拮抗剂，与管紧张素II竞争性结合AT1受体，IC50为20 nM。IC & Target IC50: 20 nM (angiotensin II)体外研究 Losartan competes with the binding of angiotensin II to AT1 receptors. The concentration that inhibits 50% of thebinding of angiotensin II (IC50) is 20 nM1. Losartan (40 M) af

6、fects 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 compared to each drug alone3.体内研究 Losartan (0.6 g/L, p.o.

7、) -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 comparablehemodynamic effects. Analysis of pSmad2 nuclear staining reveals that losartan antagonizes TGF- signaling

8、 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 angiotensinlevels four- to sixfold. Losartan (10 mg/kg, i.p.) increases plas

9、ma 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 assay, 5000 cells in 200 L media per well areseeded in a 96 well plate. Afte

10、r 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 is added to dissolve formazan crystals. Absorbance at 570 nm and at 600 nm a

11、s 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 only.Animal Female Fbn1C1039G/+ mice undergo timed matings with wild-type mal

12、e 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 lactation and after weaning until 10 months of age. Mice aresacrificed and ex

13、amined 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 root in MFS. Beginning at 7 weeks of age, wild-type and Fbn1C1039G/+ mice a

14、re 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 of these methods. They are for reference only.户使本产品发表的科研献 Cell Death Dis. 2

15、020 May 22;11(5):390.Page 2 of 3 www.MedChemE 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 validations on HYPERLINK www.MedChemE www.MedChemEREFERENCE

16、S1. 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. Choi, C.H., et al. Angiotensin II type I receptor

17、 and miR-155 in endometrial cancers: synergistic antiproliferative effects of anti-miR-155 and losartan onendometrial cancer cells. Gynecol Oncol, 2012. 126(1): p. 124-31.4. 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 C