Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate
Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate
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DOI：
10.1021/acsmedchemlett.6b00238
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发表时间：
2016-09-01
影响因子：
4.2
通讯作者：
Castro, Alfredo C.
中科院分区：
文献类型：
--
作者：
Evans, Catherine A.;Liu, Tao;Castro, Alfredo C.
优化了异喹啉酮类PI3K抑制剂，发现了一种有效的PI3K- γ抑制剂（26或IPI-549），其选择性比其他脂质和蛋白激酶高100倍。IPI-549在体内表现出良好的药代动力学特性和对pi3k - γ介导的中性粒细胞迁移的强大抑制作用，目前正在晚期实体瘤患者的1期临床评估中。
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.