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Skepinone-L 是一种选择性 p38 丝裂原活化蛋白激酶抑制剂。

Skepinone-L is a selective p38 mitogen-activated protein kinase inhibitor.

机构信息

Institute of Pharmacy, University of Tübingen, Tübingen, Germany.

出版信息

Nat Chem Biol. 2011 Dec 25;8(2):141-3. doi: 10.1038/nchembio.761.

DOI:10.1038/nchembio.761
PMID:22198732
Abstract

Until now, a lack of inhibitors with high potency and selectivity in vivo has hampered investigation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. We describe the design of skepinone-L, which is, to our knowledge, the first ATP-competitive p38 MAPK inhibitor with excellent in vivo efficacy and selectivity. Therefore, skepinone-L is a valuable probe for chemical biology research, and it may foster the development of a unique class of kinase inhibitors.

摘要

到目前为止，缺乏体内高活性和高选择性的抑制剂阻碍了对 p38 丝裂原活化蛋白激酶 (MAPK) 信号通路的研究。我们描述了 skepinone-L 的设计，据我们所知，它是第一个具有优异体内疗效和选择性的 ATP 竞争性 p38 MAPK 抑制剂。因此，skepinone-L 是化学生物学研究的有价值的探针，它可能促进一类独特的激酶抑制剂的发展。

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本文引用的文献

[1]
The Mycobacterium tuberculosis early secreted antigenic target of 6 kDa inhibits T cell interferon-γ production through the p38 mitogen-activated protein kinase pathway.

J Biol Chem. 2011-5-17

[2]
αVβ3-integrin expression through ERK activation mediates cell attachment and is necessary for production of tumor necrosis factor alpha in monocytic THP-1 cells stimulated by phorbol myristate acetate.

Cell Immunol. 2011-4-8

[3]
Macrophage migration inhibitory factor elicits an angiogenic phenotype in human ectopic endometrial cells and triggers the production of major angiogenic factors via CD44, CD74, and MAPK signaling pathways.

J Clin Endocrinol Metab. 2010-9-8

[4]
Glycogen synthase kinase-3 and p38 MAPK are required for opioid-induced microglia apoptosis.

Neuropharmacology. 2010-6-22

[5]
Rho kinase-2 activation in human endothelial cells drives lysophosphatidic acid-mediated expression of cell adhesion molecules via NF-kappaB p65.

J Biol Chem. 2010-2-17

[6]
Selective activation of the p38 MAPK pathway by synthetic monophosphoryl lipid A.

J Biol Chem. 2009-11-13

[7]
The p38alpha kinase plays a central role in inflammation.

Curr Top Med Chem. 2009

[8]
Successful structure-based design of recent p38 MAP kinase inhibitors.

Curr Top Med Chem. 2009

[9]
Signal integration by JNK and p38 MAPK pathways in cancer development.

Nat Rev Cancer. 2009-8

[10]
Hyperosmolar sodium chloride, p38 mitogen activated protein and cytokine-mediated inflammation.

Semin Dial. 2009

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