Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate

被引：125

作者：

Evans, Catherine A. ^{[1
]}

Liu, Tao ^{[1
]}

Lescarbeau, Andre ^{[1
]}

Nair, Somarajan J. ^{[1
]}

Grenier, Louis ^{[1
]}

Pradeilles, Johan A. ^{[1
]}

Glenadel, Quentin ^{[1
]}

Tibbitts, Thomas ^{[1
]}

Rowley, Ann M. ^{[1
,3
]}

DiNitto, Jonathan P. ^{[1
]}

Brophy, Erin E. ^{[1
]}

O'Hearn, Erin L. ^{[1
,2
]}

Ali, Janid A. ^{[1
]}

Winkler, David G. ^{[1
]}

Goldstein, Stanley I. ^{[1
]}

O'Heam, Patrick ^{[1
]}

Martin, Christian M. ^{[1
]}

Hoyt, Jennifer G. ^{[1
]}

Soglia, John R. ^{[1
]}

Cheung, Culver ^{[1
]}

Pink, Melissa M. ^{[1
]}

Proctor, Jennifer L. ^{[1
]}

Palombella, Vito J. ^{[1
,4
]}

Tremblay, Martin R. ^{[1
]}

Castro, Alfredo C. ^{[1
]}

机构：

[1] Infin Pharmaceut Inc, 784 Mem Dr, Cambridge, MA 02139 USA

[2] Blueprint Med, Cambridge, MA 02139 USA

[3] AbbVie, N Chicago, IL 60064 USA

[4] Surface Oncol, Cambridge, MA 02142 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2016年 / 7卷 / 09期

关键词：

IPI-549; PI3K-gamma inhibitor; phosphoinositide-3-kinase; isoform selectivity; neutrophil migration; immuno-oncology; 3-KINASE GAMMA; INFLAMMATORY DISEASES; PI3K-GAMMA; PI3K; PI3K-DELTA; POTENT; P110-DELTA; AUTOIMMUNE; RESPONSES; PATHWAY;

D O I：

10.1021/acsmedchemlett.6b00238

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：862 / 867

页数：6

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