A 779
目录号 : GC11004A 779是一种有效的选择性血管紧张素-(1-7)/ Mas受体拮抗剂,IC50值为0.3nM。
Cas No.:159432-28-7
Sample solution is provided at 25 µL, 10mM.
A 779 is a potent and selective angiotensin-(1-7)/Mas receptor antagonist with an IC50 value of 0.3nM[1]. Angiotensin-(1–7) (Ang-(1-7)) is an endogenous ligand for the G protein-coupled receptor, a bioactive peptide within the renin-angiotensin system (RAS) that significantly contributes to maintaining cardiovascular homeostasis and hydroelectrolyte balance in physiological and pathologic conditions[1][2]. A 779 inhibit the biological effects of Ang-(1-7) by binding to the G protein-coupled receptor Mas receptor (MasR)[3].
In vitro, pretreatment of human umbilical vein endothelial cells (HUVECs) with 1μM A 779 for 30 minutes significantly inhibited Ang-(1-7)’s effect on attenuating ox-LDL induced injury by modulating the specific Mas receptors[4]. Treatment of mouse islet β-cell line MIN6 cells with 1nM A 779 for 48h reverse Ang-(1-7) ’s effect on preventing high glucose-induced pathological dedifferentiation of pancreatic β-cell[5].
In vivo, A 779 considerably eradicate the defensive properties of Ang-(1-7) on bone metabolism, mineralization and micro-structure after it was delivered at infusion rate of 400ng kg−1 min−1 for 6 weeks in an ovariectomized (OVX) rodent model of osteoporosis[6][7]. Subcutaneous injection of A 779(80μg/kg) block the inhibitory effects of angiotensin converting enzyme 2 (ACE2) on endoplasmic reticulum stress (ERS) and pyroptosis in Ventilator-induced lung injury[8].
References:
[1] Santos RA, Simoes e Silva AC, Maric C, et al. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 2003;100(14):8258-8263.
[2] Maia LG, Ramos MC, Fernandes L, de Carvalho MH, Campagnole-Santos MJ, Souza dos Santos RA. Angiotensin-(1-7) antagonist A-779 attenuates the potentiation of bradykinin by captopril in rats. J Cardiovasc Pharmacol. 2004;43(5):685-691.
[3 Santos RA, Campagnole-Santos MJ, Baracho NC, et al. Characterization of a new angiotensin antagonist selective for angiotensin-(1-7): evidence that the actions of angiotensin-(1-7) are mediated by specific angiotensin receptors. Brain Res Bull. 1994;35(4):293-298.
[4] Yan WF, Xue JJ, Yang HY, Liang B, Yang ZM. Effects and related mechanism of angiotensin-(1-7) on Toll-like receptor 4-mediated oxidative stress in human umbilical vein endothelial cells. Zhonghua Xin Xue Guan Bing Za Zhi. 2017;45(3):223-229.
[5] Guo H, Guo D, An M, Zhang R, Wang C, He J. Angiotensin-(1-7) Improves Islet β-cell Dedifferentiation by Activating PI3K/Akt/FoxO1 Pathway. Protein Pept Lett. 2023;30(12):1009-1019.
[6] Abuohashish HM, Ahmed MM, Sabry D, Khattab MM, Al-Rejaie SS. Angiotensin (1-7) ameliorates the structural and biochemical alterations of ovariectomy-induced osteoporosis in rats via activation of ACE-2/Mas receptor axis. Sci Rep. 2017;7(1):2293.
[7] Abuohashish HM, Ahmed MM, Sabry D, Khattab MM, Al-Rejaie SS. ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats. Biomed Pharmacother. 2017;92:58-68.
[8] Lin X, Zhuang Y, Gao F. ACE2 Alleviates Endoplasmic Reticulum Stress and Protects against Pyroptosis by Regulating Ang1-7/Mas in Ventilator-Induced Lung Injury. Front Biosci (Landmark Ed). 2024;29(9):334.
A 779是一种有效的选择性血管紧张素-(1-7)/ Mas受体拮抗剂,IC50值为0.3nM[1]。血管紧张素-(1-7)(Ang-(1-7))是G蛋白偶联受体的内源性配体,是肾素-血管紧张素系统(RAS)中的一种生物活性肽,在生理和病理条件下对维持心血管稳态和水电解质平衡有重要作用[1][2]。A 779通过与G蛋白偶联受体MasR结合抑制Ang-(1-7) 的生物学效应[3]。
在体外实验中,1μM A 779预处理人脐静脉内皮细胞(HUVECs)30min,可通过调节特异性Mas受体显著抑制Ang-(1-7) 减弱ox-LDL诱导的损伤的作用[4]。用1nM A 779处理小鼠胰岛β-细胞系MIN6细胞48小时,可逆转Ang-(1-7)抑制高糖诱导的胰腺β-细胞病理性去分化的作用[5]。
在体内,在去卵巢(OVX)啮齿动物骨质疏松模型中以400ng kg−1 min−1的速率持续输注A 779 6周后,A 779显著消除了Ang-(1-7)对骨代谢、微结构和矿化的保护作用[6][7]。在呼吸机所致肺损伤小鼠模型中,皮下注射A 779(80μg/kg)可阻断血管紧张素转换酶2 (ACE2)对内质网应激(ERS)和焦亡的抑制作用[8]。
Cell experiment [1]: | |
Cell lines | MIN6 cells |
Preparation Method | Mouse pancreatic β-cell line MIN6 cells were digested with 0.25% trypsin into individual cells and passaged at a ratio of 1:3. Following groups were made: (1) Normal control group (Con, 11.1mM glucose), (2) high glucose group (HG group, 33.3mM glucose), (3) HG+ Ang-(1-7) group [33.3mM glucose + 1nM Ang-(1-7)], (4) HG+ Ang-(1-7)+ A 779 group (33.3mM glucose + 1nM Ang-(1-7) + 1nM A 779), and (5) HG+ Ang-(1-7) + LY294002 group (33.3mM glucose + 1nM Ang-(1-7) + 50uM LY294002). Four replicate wells were used in each group. After 48h of cell culture in each group, the expression levels of cell-specific markers Pdx1, MafA, Oct4 and Nanog in each group were detected by Real-time PCR and Western blot. The expression levels of pathway-related proteins Akt, p-Akt, FoxO1, and p-FoxO1 protein levels in each group were detected by Western blot. |
Reaction Conditions | 1nM ; 48h |
Applications | A 779 reverse Ang-(1-7) ’s effect on preventing high glucose-induced pathological dedifferentiation of pancreatic β-cell. |
Animal experiment [2]: | |
Animal models | C57BL/6 male mice |
Preparation Method | Ventilator-induced lung injury (VILI) I was induced in mice by mechanical ventilation (MV) by regulating the tidal volume. Endoplasmic reticulum stress (ERS) was inhibited by tracheal instillation of 4-phenylbutyric acid (4-PBA) (1 mg/kg). ACE2’s enzymatic function was activated or inhibited by subcutaneous injection of resorcinolnaphthalein (RES, 20µg/kg) or MLN-4760 (20µg/kg). pGLV-EF1a-GFP-ACE2 was instilled into the trachea to increase the protein expression of ACE2. The Ang (1-7) receptor, Mas, was antagonized by injecting A 779 subcutaneously (80µg/kg) 6h before MV. Then ACE2 protein levels, Ang-(1-7) levels and ERS were detected. |
Dosage form | 80µg/kg; s.c. |
Applications | A 779 blocked the inhibitory effects of angiotensin converting enzyme 2 (ACE2) on endoplasmic reticulum stress (ERS) in Ventilator-induced lung injury. |
References: |
Cas No. | 159432-28-7 | SDF | |
化学名 | (2R,3Z,5S,6Z,8S,9Z,11S,12Z,14S,15Z,17S,18Z,20S)-5-((1H-imidazol-5-yl)methyl)-20-amino-8-((S)-sec-butyl)-17-(3-guanidinopropyl)-4,7,10,13,16,19-hexahydroxy-11-(4-hydroxybenzyl)-14-isopropyl-2-methyl-3,6,9,12,15,18-hexaazadocosa-3,6,9,12,15,18-hexaene-1,22- | ||
Canonical SMILES | CC[C@]([C@@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](/N=C(O)/[C@](N)([H])CC(O)=O)([H])CCCNC(N)=N)([H])C(C)C)([H])CC1=CC=C(O)C=C1)([H])/C(O)=N/[C@@](/C(O)=N/[C@](C(O)=O)([H])C)([H])CC2=CN=CN2)([H])C | ||
分子式 | C39H60N12O11 | 分子量 | 872.97 |
溶解度 | ≥ 29.1mg/mL in Water with gentle warming | 储存条件 | Store at -20°C |
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10 mM | 0.1146 mL | 0.5728 mL | 1.1455 mL |
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