AVE-0991-sodium-salt - Angiotensin Receptor Agonist - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAVE 0991 sodium saltCat. No.: HY-15778ACAS No.: 306288-04-0分式: CHNNaOS分量: 602.7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 : 55 mg/mL (91.26 mM

2、)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.6592 mL 8.2960 mL 16.5920 mL5 mM 0.3318 mL 1.6592 mL 3.3184 mL10 mM 0.1659 mL 0.8296 mL 1.6592 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 AVE 0991 sodium salt种有效的肽Ang-(1-7) 受体 Mas

3、激动剂。AVE 0991 与 125I-Ang-(1-7) 竞争性地结合到主动脉内细胞膜，IC50 为 2135 nM。IC50 & Target IC50: 2135 nM (Ang-(1-7) receptor) 1体外研究AVE 0991 is a nonpeptide compound that evokes effects similar to Ang-(1-7) on the endothelium. AVE 09911/3 Master of Small Molecules 您边的抑制剂师www.MedChemEand unlabeled Ang-(1-7) compete fo

4、r high-affinity binding of 125I-Ang-(1-7) to bovine aortic endothelial cellmembranes with IC50s of 2135 and 220280 nM, respectively. Peak concentrations of NO and O2- releaseby AVE 0991 sodium salt and Ang-(1-7) (both 10 M) are not significantly different (NO: 29520 and 27025nM; O2-: 182 and 204 nM)

5、. However, the released amount of bioactive NO is 5 times higher for AVE0991 in comparison to Ang-(1-7) 1.体内研究 AVE 0991 (0.58 nmol/g) produces a significant decrease of water diuresis in WT mice compared withvehicle-treated animals (0.060.03 mL versus 0.270.05; n=9 for each group; P2O versus 681.116

6、5.8mOsm/KgH2O in vehicle-treated mice; PMas abolishes the antidiuretic effect of AVE 0991 during waterloading (0.370.10 mL n=9 versus 0.270.03 mL n=11 in AVE 0991-treated mice). As observed withC57BL/6 mice, administration of AVE 0991 (0.58 nmol/g) in water-loaded Swiss mice also produces asignifica

7、nt decrease of the urinary volume compared with vehicle-treated animals (0.130.05 mL n=16versus 0.510.04 mL n=40; P 2. One week of treatment with AVE-0991 produces a significant decrease inperfusion pressure (56.550.86 vs. 68.730.69 mmHg in vehicle-treated rats) and an increase in systolictension (1

8、1.400.05 vs. 9.840.15 g in vehicle-treated rats), rate of tension rise (+dT/dt; 184.300.50 vs.155.201.97 g/s in vehicle-treated rats), rate of tension fall (dT/dt; 179.601.39 vs. 150.802.42 g/s invehicle-treated rats). A slight increase in heart rate (HR) is also observed (220.400.71 vs. 214.200.74b

9、eats/min in vehicle-treated rats 3.PROTOCOLKinase Assay 1 Binding of 125I-Ang-(1-7) is performed. Briefly, 100 g of membranes from primary cultured bovine aorticendothelial cells (BAECs, passage 1) are incubated in a total volume of 200 L for 45 minutes at 25C inHEPES-buffered saline (10 mM HEPES, 0

10、.1 M NaCl, 5 mM MgCl2) containing 0.2% BSA and proteaseinhibitor cocktail Complete (Boehringer Mannheim). Saturable binding of 125I-Ang-(1-7) is calculated bysubtracting nonspecific binding (40% to 50%), determined in the presence of 10 M unlabeled Ang-(1-7) fromtotal binding. Competition experiment

11、s with increasing concentrations of AVE 0991 and unlabeled Ang-(1-7)are performed in the presence of 10 nM 125I-Ang-(1-7). Assays are terminated by vacuum filtration (15mm Hg) over Durapore filters (0.65 m, Opak 96-well plates) presoaked with 1% BSA. The filters are washed3 times with each 100 L of

12、PBS (50 mM, NaHPO4 and 0.15 M NaCl, pH 7.2). Radioactivity on dried filters isquantified with a gamma counter 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 23 Swiss male mice, Mas-KO (Mas-/-) male mice on the pure genetic

13、 background C57BL/6, and WT C57BL/6control mice (Mas+/+) are used. Water diuresis is induced by intraperitoneal water injection (0.05 mL/g ofbody weight BW) in conscious mice. Drugs are administered in the same injection with water load atprefixed volumes (0.01 mL/g BW). In the first set of experime

14、nts, WT mice (C57BL/6, control group) or Mas-KO mice are treated with: (1) 0.58 nmol/g AVE 0991 (n=9, control; n=11, Mas-KO mice); or (2) vehicle forAVE 0991 (10 M KOH, 0.01 mL/g; n=9, control; n=9, Mas-KO). In the second set, Swiss mice are treatedwith: (1) vehicle (n=36); (2) 0.58 nmol/g AVE 0991

15、(n=16); (3) 46 pmol/g Ang-(1-7) antagonist A-779 (n=4);(4) 2 nmol/g losartan or valsartan (n=5); (5) 2 nmol/g AT2 receptor antagonists PD123319 or PD123177(n=9); (6) AVE 0991 combined with A-779; (7) AVE 0991 combined with losartan or valsartan (n=4 for each);2/3 Master of Small Molecules 您边的抑制剂师www

16、.MedChemE(8) or AVE 0991combined with PD123319 (n=5) or PD123177 (n=4). The urinary volume is measured for 60minutes after water loading, and urine samples are obtained to determine the osmolality. The dose of AVE0991is based in preliminary experiments performed in Swiss mice.Rats 3Male Wistar rats

17、weighting 250-300 g are used. Rats are treated either with AVE-0991 (1 mg/kg, n=9) orvehicle (0.9% NaCl, n=11) administered orally by gavage. At the end of the 7 day period of AVE-0991treatment, the animals are decapitated 10-15 min after intraperitoneal injection of 400 IU of heparin. After thethor

18、ax is opened, the heart is carefully dissected, removed from the thoracic cavity, and placed in a platecontaining ice-cold Krebs-Ringer solution (KRS) to attenuate any potential cardiac damage during dissectionof aorta artery.MCE has not independently confirmed the accuracy of these methods. They ar

19、e for reference only.户使本产品发表的科研献 Blood. 2015 Jan 22;125(4):710-9. Redox Biol. 2019 Jan;20:75-86. Diabetes. 2017 Aug;66(8):2201-2212. Aging (Albany NY). 2018 Apr 17;10(4):645-657. PLoS One. 2015 Nov 5;10(11):e0142087.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Wiemer G, et al. AVE 0991, a nonpeptide mimic of the eff