Isoform-selective PI3K inhibitors as novel therapeutics for the treatment of acute myocardial infarction.
In the present paper, we review the preclinical development of TG100-115, a PI3K (phosphoinositide 3-kinase) 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.
Doukas
J
J
TargeGen Inc, San Diego, CA 92121, USA. jdoukas@targegen.com
Wrasidlo
W
W
Noronha
G
G
Dneprovskaia
E
E
Hood
J
J
Soll
R
R
D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D009203:Myocardial Infarction / Q000188:drug therapy*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D000081082:Phosphoinositide-3 Kinase Inhibitors