Isoform-selective PI3K inhibitors as novel therapeutics for the treatment of acute myocardial infarction

被引：20
作者：
Doukas, J. [1 ]
Wrasidlo, W. [1 ]
Noronha, G. [1 ]
Dneprovskaia, E. [1 ]
Hood, J. [1 ]
Soll, R. [1 ]
机构：
[1] TargeGen Inc, San Diego, CA 92121 USA
来源：
BIOCHEMICAL SOCIETY TRANSACTIONS | 2007年 / 35卷
关键词：
inflammation; ischaemia; myocardial infarction; oedema; phosphoinositide 3-kinase (PI3K);
D O I：
10.1042/BST0350204
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：
In the present paper, we review the preclinical development of TG100-115, a PI3K (phosphoinositide 3kinase) gamma/delta isoform-specific inhibitor currently in clinical trials for the reduction of acute MI (myocardial infarction). An overview is presented outlining the pathogenesis of acute MI and the rationale for clinical use of PI3K gamma/delta-specific inhibitors in this indication. TG100-115's broad anti-inflammatory activities are described, as well as its ability to discriminate between cellular signalling pathways downstream of receptor tyrosine kinase ligands such as vascular endothelial growth factor. Finally, we review TG100-115's potent cardioprotective activities as revealed in rigorous animal models of acute MI, and, based on these data, this compound's potential for clinical utility.
引用
收藏
页码：204 / 206
页数：3
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