Novel IKK inhibitors:: β-carbolines

被引：227

作者：

Castro, AC ^{[1
]}

Dang, LC ^{[1
]}

Soucy, F ^{[1
]}

Grenier, L ^{[1
]}

Mazdiyasni, H ^{[1
]}

Hottelet, M ^{[1
]}

Parent, L ^{[1
]}

Pien, C ^{[1
]}

Palombella, V ^{[1
]}

Adams, J ^{[1
]}

机构：

[1] Millennium Pharmaceut Inc, Cambridge, MA 02139 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 14期

关键词：

D O I：

10.1016/S0960-894X(03)00408-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Inhibitors of IkappaB kinase (IKK) have long been sought as specific regulators of NF-kappaB. A screening effort of the endogenous IKK complex allowed us to identify 5-bromo-6-methoxy-beta-carboline as a nonspecific IKK inhibitor. Optimization of this beta-carboline natural product derivative resulted in a novel class of selective IKK inhibitors with IC(50)s in the nanomolar range. In addition. we show that one of these beta-carboline analogues inhibits the phosphorylation of IkappaBalpha and subsequent activation of NF-kappaB in whole cells, as well as blocking TNF-alpha release in LPS-challenged mice. (C) 2003 Elsevier Science Ltd. All rights reserved.

引用

页码：2419 / 2422

页数：4

共 15 条

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