A high throughput screen identifies potent and selective inhibitors to human epithelial 15-lipoxygenase-2.
A high throughput screen identifies potent and selective inhibitors to human epithelial 15-lipoxygenase-2.
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DOI：
10.1371/journal.pone.0104094
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Holman TR
中科院分区：
文献类型：
--
作者：
Jameson JB 2nd;Kantz A;Schultz L;Kalyanaraman C;Jacobson MP;Maloney DJ;Jadhav A;Simeonov A;Holman TR
Lipoxygenase (LOX) enzymes catalyze the hydroperoxidation of arachidonic acid and other polyunsaturated fatty acids to hydroxyeicosatetraenoic acids with varying positional specificity to yield important biological signaling molecules. Human epithelial 15lipoxygenase2 (15-LOX-2) is a highly specific LOX isozyme that is expressed in epithelial tissue and whose activity has been correlated with suppression of tumor growth in prostate and other epithelial derived cancers. Despite the potential utility of an inhibitor to probe the specific role of 15-LOX-2 in tumor progression, no such potent/specific 15LOX2 inhibitors have been reported to date. This study employs high throughput screening to identify two novel, specific 15LOX2 inhibitors. MLS000545091 is a mixed-type inhibitor of 15-LOX-2 with a Ki of 0.9+/−0.4 µM and has a 20-fold selectivity over 5-LOX, 12-LOX, 15-LOX-1, COX-1, and COX-2. MLS000536924 is a competitive inhibitor with a Ki of 2.5+/−0.5 µM and also possesses 20-fold selectivity toward 15-LOX-2 over the other oxygenases, listed above. Finally, neither compound possesses reductive activity towards the active-site ferrous 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
影响因子：
8
作者：
Suraneni, M. V.;Schneider-Broussard, R.;Moore, J. R.;Davis, T. C.;Maldonado, C. J.;Li, H.;Newman, R. A.;Kusewitt, D.;Hu, J.;Yang, P.;Tang, D. G.
通讯作者：
Tang, D. G.
影响因子：
5.1
作者：
Robinson, Sarah J.;Hoobler, Eric K.;Riener, Michelle;Loveridge, Steven T.;Tenney, Karen;Valeriote, Frederick A.;Holman, Theodore R.;Crews, Phillip
通讯作者：
Crews, Phillip
影响因子：
7.3
作者：
Kenyon, Victor;Rai, Ganesha;Holman, Theodore R.
通讯作者：
Holman, Theodore R.
影响因子：
7.3
作者：
Sherman, W;Day, T;Farid, R
通讯作者：
Farid, R