Novel IKK inhibitors: beta-carbolines.
Basic Information
ID: ALA1136119
Journal: Bioorg Med Chem Lett
Title: Novel IKK inhibitors: beta-carbolines.
Authors: Castro AC, Dang LC, Soucy F, Grenier L, Mazdiyasni H, Hottelet M, Parent L, Pien C, Palombella V, Adams J.
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.
CiteXplore: 12824047
DOI: 10.1016/s0960-894x(03)00408-6
Patent ID: ┄