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Bioorg Med Chem Lett. 2003 Jul 21;13(14):2419-22.

Novel IKK inhibitors: beta-carbolines.

Author information

1
Millennium Pharmaceuticals Inc., 35 Landsdowne Street, 02139, Cambridge, MA, USA.

Abstract

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.

PMID:
12824047
DOI:
10.1016/s0960-894x(03)00408-6
[Indexed for MEDLINE]

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