体外研究
Endothelin converting enzyme (ECE) inhibitors, WS75624A and (±)-WS75624B, have been isolated from the fermentation broth of
Saccharothrix
sp. No. 75624. WS75624A and (±)-WS75624B show highly potent ECE inhibitory activity, and both have IC
50
s of 0.03 μg/mL. WS75624A and (±)-WS75624B also show other metalloprotease (collagenase and neutral endopeptidase) inhibitory activity with IC
50
s of 1 μg/mL. (±)-WS75624B markedly inhibits ECE activity with an IC
50
value of 0.03 μg/mL, while it weakly inhibit collagenase and NEP activities with IC
50
s of 1.0 μg/mL and 1.25 μg/mL, respectively.
体内研究
(±)-WS75624B inhibits big endothelin-induced pressor effect when administered to SD rat intravenously with big ET-1. WS75624 B (30 mg/kg) markedly attenuates the hypertensive effect of big ET-1 (1 nmol/kg,iv) the inhibiting the conversion of big ET-1 to ET-1.
