Journal
BIOCHEMICAL SOCIETY TRANSACTIONS
Volume 35, Issue -, Pages 204-206Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BST0350204
Keywords
inflammation; ischaemia; myocardial infarction; oedema; phosphoinositide 3-kinase (PI3K)
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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.
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