Discovery of potent and selective inhibitors of human reticulocyte 15-lipoxygenase-1.
Discovery of potent and selective inhibitors of human reticulocyte 15-lipoxygenase-1.
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DOI：
10.1021/jm1008852
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发表时间：
2010-10-28
影响因子：
7.3
通讯作者：
Maloney DJ
中科院分区：
文献类型：
--
作者：
Rai G;Kenyon V;Jadhav A;Schultz L;Armstrong M;Jameson JB;Hoobler E;Leister W;Simeonov A;Holman TR;Maloney DJ
There are a variety of lipoxygenases in the human body (hLO), each having a distinct role in cellular biology. Human reticulocyte 15-Lipoxygenase-1 (15-hLO-1), which catalyzes the dioxygenation of 1,4-cis,cis-pentadiene-containing polyunsaturated fatty acids, is implicated in a number of diseases including cancer, atherosclerosis, and neurodegenerative conditions. Despite the potential therapeutic relevance of this target, few inhibitors have been reported that are both potent and selective. To this end, we have employed a quantitative high-throughput (qHTS) screen against ~74,000 small molecules in search of reticulocyte 15-hLO-1 selective inhibitors. This screen led to the discovery of a novel chemotype for 15-hLO-1 inhibition, which displays nM potency and is >7,500-fold selective against the related isozymes, 5-hLO, platelet 12-hLO, epithelial 15-hLO-2, ovine cyclooxygenase-1 and human cyclooxygenase-2. In addition, kinetic experiments were performed which indicate that this class of inhibitor is tight binding, reversible, and appears not to reduce the active-site ferric ion.
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影响因子：
5.1
作者：
Amagata, T;Whitman, S;Holman, TR
通讯作者：
Holman, TR
DOI：
10.1111/j.1742-1241.2007.01320.x
发表时间：
2007-04-01
影响因子：
2.6
作者：
Berger, W.;De Chandt, M. T. M.;Cairns, C. B.
通讯作者：
Cairns, C. B.
影响因子：
--
作者：
HUSSAIN, H;SHORNICK, LP;HOLTZMAN, MJ
通讯作者：
HOLTZMAN, MJ
影响因子：
--
作者：
Eastwood, BJ;Farmen, MW;Smith, GF
通讯作者：
Smith, GF
影响因子：
2.9
作者：
Choi, Jongkeun;Chon, Jae Kyung;Shin, Whanchul
通讯作者：
Shin, Whanchul