Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 7, Issue 9, Pages 862-867Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.6b00238
Keywords
IPI-549; PI3K-gamma inhibitor; phosphoinositide-3-kinase; isoform selectivity; neutrophil migration; immuno-oncology
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Optimization of isoquinolinone PI3K inhibitors led to the discovery of a potent inhibitor of PI3K-gamma (26 or IPI-549) with >100-fold selectivity over other lipid and protein kinases. IPI-549 demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K-gamma mediated neutrophil migration in vivo and is currently in Phase 1 clinical evaluation in subjects with advanced solid tumors.
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