A 779

A 779 is a specific antagonist of G-protein coupled receptor (Mas receptor), which is an Ang1-7 receptor distinct from the classical AngII.

Product information

CAS Number: 159432-28-7

Molecular Weight: 872.97

Formula: C39H60N12O11

Chemical Name: (3S)-3-amino-3-{[(1S)-4-carbamimidamido-1-{[(1S)-1-{[(1S)-1-{[(1S,2S)-1-{[(1S)-1-{[(1R)-1-carboxyethyl]carbamoyl}-2-(1H-imidazol-4-yl)ethyl]carbamoyl}-1-hydrogenio-2-methylbutyl]carbamoyl}-2-(4-hydroxyphenyl)ethyl]carbamoyl}-2-methylpropyl]carbamoyl}butyl]carbamoyl}propanoic acid

Smiles: CC(C)[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@H](C)C(O)=O

InChiKey: GZSZZUXDAPDPOR-NGIFJXEWSA-N

InChi: InChI=1S/C39H60N12O11/c1-6-20(4)31(37(60)49-28(15-23-17-43-18-45-23)34(57)46-21(5)38(61)62)51-35(58)27(14-22-9-11-24(52)12-10-22)48-36(59)30(19(2)3)50-33(56)26(8-7-13-44-39(41)42)47-32(55)25(40)16-29(53)54/h9-12,17-21,25-28,30-31,52H,6-8,13-16,40H2,1-5H3,(H,43,45)(H,46,57)(H,47,55)(H,48,59)(H,49,60)(H,50,56)(H,51,58)(H,53,54)(H,61,62)(H4,41,42,44)/t20-,21+,25-,26-,27-,28-,30-,31-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: H2O : 50 mg/mL (57.28 mM; Need ultrasonic).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

A-779 inhibits the effect of Ang-(1-7), which suppresses the proliferating cell nuclear antigen (PCNA) protein expression up-regulated by Ang II, but A-779 alone has no effect to induce proliferation and migration of VSMCs. Pretreatment with Ang-(1-7) significantly retards Ang II-induced inflammatory responses of VSMCs associated with up-regulated MCP-1, VCAM-1 and IL-1β expressions, and this effect of Ang-(1-7) is blocked by A-779. But A-779 alone has no effect to induce inflammatory response of VSMCs. Pretreatment VSMCs with Ang-(1-7) for 5 min significantly inhibits Akt and ERK1/2 phosphorylation induced by Ang II, and this effect is also blocked by A-779, but alone has no effect to induce phosphorylation of Akt and ERK1/2 in VSMCs.

In Vivo:

Infusion of Ang(1-7) and A-779 (400 ng/kg/min, s.c.) alone or combined for 6 weeks does not prevent uterus atrophy or inhibit the body weight gain of OVX rats. A-779 markedly elevates serum bone specific alkaline phosphatase (BALP), telopeptides of collagen type I (CTX), tartarate resistant acid phosphatase (TRAcP 5b), osteocalcin (OC) and urinary deoxypyridinoline (DPD). Infusion of Ang(1-7) and/or A-779 does not significantly change serum minerals concentrations in sham or OVX groups. A-779 in the OVX animals does not change AngII, Ang(1-7), AT1R, AT2R, ACE, ACE-2, Mas receptor, RANKL and OPG proteins expressions in relation to OVX group, while AngII (P 

References:

1. Abuohashish HM, et al. 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 May 23;7(1):2293.
2. Abuohashish HM, et al. ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic 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 umbilical vein endothelial cells. Zhonghua Xin Xue Guan Bing Za Zhi. 2017 Mar 24;45(3):223-229.

Products are for research use only. Not for human use.