A-216546
A-216546 性质
| 沸点 | 636.9±55.0 °C(Predicted) |
|---|---|
| 密度 | 1.097±0.06 g/cm3(Predicted) |
| 酸度系数(pKa) | 3.58±0.60(Predicted) |
A-216546 用途与合成方法
|
ET A 0.46 nM (Ki) |
ABT-546 (A-216546) effectively inhibits specific I endothelin-1 binding to endothelin ET
A
receptor in membranes prepared from rat pituitary MMQ cells with an IC
50
value of 0.56 nM. ABT-546 is much less effective in inhibiting specific [
125
I]endothelin-3 binding to endothelin ET
B
rceptor in membranes prepared from porcine cerebellum with an IC
50
value of 16,700 nM. In membranes prepared from CHO cells stably transfected with the human endothelin ET
A
and ET
B
receptors, ABT-546 again effectively inhibits specific [
125
I]endothelin-1 binding to endothelin ET
A
receptor with an IC
50
value of 0.49 nM, but is less effective in inhibiting specific [
125
I]endothelin-3 binding to endothelin ET
B
receptor with an IC
50
value of 15,400 nM.
In isolated vessels, ABT-546 inhibits endothelin ET
A
receptor-mediated endothelin-1-induced vasoconstriction, and endothelin ET
B
receptor-mediated sarafotoxin 6c-induces vasoconstriction with pA
2
of 8.29 and 4.57, respectively.
ABT-546 (A-216546; 0-100 mg/kg; oral administration; for 1 hour or 4 hours; male Sprague-Dawley rats) treatment dose-dependently blocks endothelin-1-induced pressor response in conscious rats.
| Animal Model: | Male Sprague-Dawley rats (250-350 g) induced with endothelin-1 |
| Dosage: | 0.1 mg/kg, 1 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg |
| Administration: | Oral administration; for 1 hour or 4 hours |
| Result: | Exhibited a dose-dependent inhibition of the peak pressor response to endothelin-1, and statistically significant inhibition was achieved at doses of 3 to 100 mg/kg. |
