Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621:: in vitro studies

被引：30

作者：

Wu-Wong, JR ^{[1
]}

Dixon, DB ^{[1
]}

Chiou, WJ ^{[1
]}

Sorensen, BK ^{[1
]}

Liu, G ^{[1
]}

Jae, HS ^{[1
]}

Tasker, A ^{[1
]}

von Geldern, TW ^{[1
]}

Winn, M ^{[1
]}

Opgenorth, TJ ^{[1
]}

机构：

[1] Abbott Labs, Div Pharmaceut Prod, Abbott Pk, IL 60064 USA

来源：

CLINICAL SCIENCE | 2002年 / 103卷

关键词：

A-182086; A-192621; ABT-546; ABT-627; atrasentan; endothelin; endothelin receptor; endothelin receptor antagonist;

D O I：

10.1042/CS103S107S

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Endothelins (ETs), 21-amino-acid peptides involved in the pathogenesis of various diseases, bind to ETA and ETB receptors to initiate their effects. Based on the same core structure, we have developed four small-molecule ET receptor antagonists, ABT-627, ABT-546, A-182086 and A-192621, which exhibit difference in selectivity for ETA and ETB receptors. In this report, we compare the potency and selectivity of these four antagonists in inhibiting I-125-labelled ET-1 binding to cloned human ETA and ETB receptors, and in blocking ET-1-induced functional responses (arachidonic acid release and phosphatidylinositol hydrolysis).

引用

页码：107S / 111S

页数：5

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