Synthesis and biological activity of a focused library of mitogen-activated protein kinase phosphatase inhibitors

被引：16

作者：

Arnold, David M.

Foster, Caleb

Huryn, Donna M.

Lazo, John S.

Johnston, Paul A.

Wipf, Peter ^{[1
]}

机构：

[1] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA

[2] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA

[3] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA

[4] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15260 USA

[5] Univ Pittsburgh, Pittsburgh Mol Lib Screening Ctr, Pittsburgh, PA 15260 USA

来源：

CHEMICAL BIOLOGY & DRUG DESIGN | 2007年 / 69卷 / 01期

关键词：

dual-specificity phosphatase; inhibitor synthesis; library synthesis; mitogen-activated protein kinase phosphatase-1; Molecular Libraries Screening Center Network; PubChem; quinolines; uracils;

D O I：

10.1111/j.1747-0285.2007.00474.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mitogen-activated protein kinase phosphatase 1 is a tyrosine phosphatase superfamily member that dephosphorylates and inactivates mitogen-activated protein kinase substrates, such as p38, c-Jun-N-terminal kinase, and extracellular signal-related kinase. These mitogen-activated protein kinase substrates regulate many cellular processes associated with human diseases. In spite of this potential as a molecular target for chemotherapy, however, pharmacologically tractable inhibitors of mitogen-activated protein kinase phosphatase-1 have yet to be developed. Based on the results from a high-throughput screen for small molecule inhibitors of mitogen-activated protein kinase phosphatase-1, we designed, synthesized, and evaluated a focused library in an effort to further understand the structural requirements for mitogen-activated protein kinase phosphatase-1 inhibitory activity.

引用

页码：23 / 30

页数：8

共 16 条

[1] MAPK-specific tyrosine phosphatases: new targets for drug discovery? [J].