AVE 0991

Description

AVE 0991 is an orally active, non-peptide angiotensin (1-7) receptor agonist with an IC50 of 21 nM.

IC50 and target

IC50: 21 ± 35 nM (receptor Ang- (1-7))

In vitro

AVE 0991 is a non-peptide compound that evokes Ang- (1-7) -like effects on the endothelium. AVE 0991 and unlabeled Ang- (1-7) compete for high-affinity binding of -Ang- (1-7) to bovine aortic endothelial cell membranes with IC50s of 21 ± 35 and 220 ± 280 nM, respectively.

The maximum concentrations of NO and O2 release by the sodium salt AVE 0991 and Ang- (1-7) (both 10 μM) are not significantly different (NO: 295 ± 20 and 270 ± 25 nM; O2-: 18 ± 2 and 20 ± 4 nM). However, the amount of bioactive NO released is ~ 5 times higher for AVE 0991 compared to Ang- (1-7). MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Live

AVE 0991 (0.58 nmol / g) produces a significant decrease in water diuresis in WT mice compared to vehicle treated animals (0.06 ± 0.03 ml vs 0.27 ± 0.05; n = 9 for each group; P <0.01). The antidiuretic effect of AVE 0991 (AVE) is associated with an increase in urine osmolality (1669 ± 231.0 mOsm / KgH2O versus 681.1 ± 165.8 mOsm / KgH2O in vehicle-treated mice; P <0 , 01).

The Mas genetic deletion nullifies the antidiuretic effect of AVE 0991 during water loading (0.37 ± 0.10 ml [n = 9] vs 0.27 ± 0.03 ml [n = 11] in mice treated with AVE 0991). As observed with C57BL / 6 mice, administration of AVE 0991 (0.58 nmol / g) in water-loaded Swiss mice also produces a significant decrease in urinary volume compared to vehicle-treated animals (0.13 ± 0.05 mL [n = 16] versus 0.51 ± 0.04 mL [n = 40]; P <0.01).

One week of treatment with AVE-0991 produces a significant decrease in perfusion pressure (56.55 ± 0.86 vs 68.73 ± 0.69 mmHg in vehicle-treated rats) and an increase in systolic pressure (11, 40 ± 0.05 vs 9.84 ± 0.15 g in vehicle-treated rats). treated rats), rate of tension increase (+ DT / DT; 184.30 ± 0.50 vs 155.20 ± 1.97 g / s in vehicle-treated rats), rate of tension drop (-DT / DT; 179.60 ± 1.39 vs 150.80 ± 2.42 g / s in vehicle-treated rats). A slight increase in heart rate (HR) is also observed (220.40 ± 0.71 vs 214.20 ± 0.74 beats/min in vehicle-treated rats. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular weight

580.72

Formula

C₂₉H₃₂N₄O₅S₂

CAS No.

304462-19-9

Smiles

O = S (C1 = C (C2 = CC = C (CN3C (C = O) = C (OC) N = C3 C4 = CC = CC = C4) C = C2) C = C (CC (C) C) S1 ) (NC (NCC) = O) = O

Transport

Ambient Temperature in Continental US; may vary elsewhere.

Storage

Dust -20 ° C 3 years
4 ° C 2 years

Insolvent -80 ° C 6 months
-20 ° C 1 month

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