Isoform selective inhibition of STAT1 or STAT3 homo-dimerization via peptidomimetic probes: Structural recognition of STAT SH2 domains

被引：47

作者：

Gunning, Patrick T.

Katt, William P.

Glenn, Matthew

Siddique, Khandaker

Kim, Joon S.

Jove, Richard

Sebti, Said M.

Turkson, James

Hamilton, Andrew D. ^{[1
]}

机构：

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

[2] Univ Cent Florida, Dept Mol Biol & Microbiol, Burnett Coll Biomed Sci, Orlando, FL 32816 USA

[3] City Hope Natl Med Ctr, Duarte, CA USA

[4] H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 07期

关键词：

STAT1; STAT3; peptidomimetics; inhibitors; anti-cancer; SH2 domain recognition;

D O I：

10.1016/j.bmcl.2007.01.077

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The identification of constitutively activated STAT (Signal Transducers and Activators of Transcription) proteins in aberrant cell signaling pathways has led to investigations targeting the selective disruption of specific STAT isoforms directly associated with oncogenisis. We have identified, through the design of a library of peptidomimetic inhibitors, agents that selectively disrupt STAT1 or STAT3 homo-dimerization at low micromolar concentrations. ISS840 has 20-fold higher inhibition of STAT1 homo-dimerization (IC50 value of 31 mu M) relative to STAT3 (IC50 value of 560 mu M). (c) 2007 Published by Elsevier Ltd.

引用

页码：1875 / 1878

页数：4

共 19 条

[1]

*ACC, QSAR MOD CER VERS 4

[2] Three-dimensional structure of the Stat3β homodimer bound to DNA [J].