A-779 - Angiotensin Receptor Antagonist - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEA 779Cat. No.: HY-P0216CAS No.: 159432-28-7分式: CHNO分量: 872.97Sequence: Asp-Arg-Val-Tyr-Ile-His-d-AlaSequence Shortening: DRVYIH-d-Ala作靶點: Angiotensin Receptor作通路: GPCR/G Protein儲存式: Powder -80C 2 years-20C 1 yearIn solvent -80C

2、6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 H2O : 50 mg/mL (57.28 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.1455 mL 5.7276 mL 11.4551 mL5 mM 0.2291 mL 1.1455 mL 2.2910 mL10 mM 0.1146 mL 0.5728 mL 1.1455 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，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 A 779G蛋偶聯(lián)受體

3、Mas的有效拮抗劑，Mas受體為種Ang1-7 receptor，區(qū)別于傳統(tǒng)的AngII。體外研究A-779 inhibits the effect of Ang-(1-7), which suppresses the proliferating cell nuclear antigen (PCNA) proteinexpression up-regulated by Ang II, but A-779 alone has no effect to induce proliferation and migration of1/3 Master of Small Molecules 您邊的抑制劑

4、師www.MedChemEVSMCs. Pretreatment with Ang-(1-7) significantly retards Ang II-induced inflammatory responses of VSMCsassociated with up-regulated MCP-1, VCAM-1 and IL-1 expressions, and this effect of Ang-(1-7) is blockedby A-779. But A-779 alone has no effect to induce inflammatory response of VSMCs

5、. Pretreatment VSMCswith Ang-(1-7) for 5min significantly inhibits Akt and ERK1/2 phosphorylation induced by Ang II, and thiseffect is also blocked by A-779, but alone has no effect to induce phosphorylation of Akt and ERK1/2 inVSMCs 3.體內(nèi)研究 Infusion of Ang(1-7) and A-779 (400ng/kg/min, s.c.) alone o

6、r combined for 6 weeks does not prevent uterusatrophy or inhibit the body weight gain of OVX rats. A-779 markedly elevates serum bone specific alkalinephosphatase (BALP), telopeptides of collagen type I (CTX), tartarate resistant acid phosphatase (TRAcP 5b),osteocalcin (OC) and urinary deoxypyridino

7、line (DPD). Infusion of Ang(1-7) and/or A-779 does notsignificantly change serum minerals concentrations in sham or OVX groups. A-779 in the OVX animals doesnot change AngII, Ang(1-7), AT1R, AT2R, ACE, ACE-2, Mas receptor, RANKL and OPG proteinsexpressions in relation to OVX group, while AngII (P 1.

8、 Inhibition of Ang1-7 cascade by A-779 (400ng/kg/min) significantly eradicates captopril protective effects on bone metabolism, mineralization and micro-structure. A-779 also restores OVX effects on RANKL expression and ACE-1/AngII/AT1R cascade anddown-regulates OPG expression and ACE-2/Ang1-7/Mas p

9、athway 2.PROTOCOLAnimal A bilateral OVX operation is use to induce postmenopausal osteoporosis in female Wistar albino rats. TheAdministration 1 animals are generally anesthetized using single IP injection of ketamine+xylazine combination (80mg/kgand 5mg/kg; respectively). After ligation, the ovarie

10、s are excised from a longitudinal incision made on thedorsolateral body region. Sham rats have the same procedure without the ligation and excision. The risk ofpostoperative infection is eliminated by applying fusidic acid topical antibiotic cream twice weekly for 4weeks. Following the sham and OVX

11、operations, animals are divided into eight groups (n=8/group)including, Sham, Sham+Ang(1-7), Sham+A-779, Sham+Ang(1-7)+A-779, OVX, OVX+Ang(1-7), OVX+A-779 and OVX+Ang(1-7)+A-779. Eight weeks following sham and OVX operations, osmotic pumps areimplanted subcutaneously to deliver Ang(1-7) (200ng/kg/mi

12、n), A-779 (400ng/kg/min) or a mixture of Ang(1-7) and A-779 (200ng/kg/min and 400ng/kg/min; respectively) for 6 consecutive weeks. Body weights of allanimals are monitored and recorded at the beginning and every week throughout the study. Animals generalhealth is maintained during periods of treatme

13、nts. At the end of treatments periods, animals are placedfasting in metabolic cages for 16hr and urine samples are collected and frozen at 70C. Then, the bloodsamples are collected by cardiac puncture under ketamine+xylazine anesthesia and serum samples areobtain by centrifugation at 4000 RPM to. An

14、imals are then sacrificed by decapitation and the uterine tissuesand femoral bones are removed and cleaned. Uterine tissues are cleaned from fats and the wet weights aredetermined directly and expressed as g/100g body weight. In each rat, both femurs are removed andcleaned from soft tissues. The lef

15、t femoral bone samples are frozen at 70C until analyzed, while the rightfemoral bones are kept in 10% formalin for mico-CT and minerals analysis.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1

16、. Abuohashish HM, et al. Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis inrats via activation of ACE-2/Mas receptor axis. Sci Rep. 2017 May 23;7(1):2293.2. Abuohashish HM, et al. ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficientosteoporotic rats. Biomed Pharmacother. 2017 Aug;92:58-68.3. Yan WF, et al. Effects and related mechanism of angiotensin-(1-7) on Toll-like receptor 4-mediated oxidative stress in human umbilicalvein endothelial cells. Zhonghu