发现一种选择性磷酸肌醇-3-激酶（PI3K）-γ抑制剂（IPI-549）作为免疫肿瘤学临床候选药物。
Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate.
作者信息
Evans Catherine A, Liu Tao, Lescarbeau André, Nair Somarajan J, Grenier Louis, Pradeilles Johan A, Glenadel Quentin, Tibbitts Thomas, Rowley Ann M, DiNitto Jonathan P, Brophy Erin E, O'Hearn Erin L, Ali Janid A, Winkler David G, Goldstein Stanley I, O'Hearn Patrick, Martin Christian M, Hoyt Jennifer G, Soglia John R, Cheung Culver, Pink Melissa M, Proctor Jennifer L, Palombella Vito J, Tremblay Martin R, Castro Alfredo C
机构信息
Infinity Pharmaceuticals, Inc. , 784 Memorial Drive, Cambridge, Massachusetts 02139, United States.
出版信息
ACS Med Chem Lett. 2016 Jul 22;7(9):862-7. doi: 10.1021/acsmedchemlett.6b00238. eCollection 2016 Sep 8.
Abstract
Optimization of isoquinolinone PI3K inhibitors led to the discovery of a potent inhibitor of PI3K-γ (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-γ mediated neutrophil migration in vivo and is currently in Phase 1 clinical evaluation in subjects with advanced solid tumors.
摘要
异喹啉酮类PI3K抑制剂的优化导致了一种PI3K-γ强效抑制剂（26或IPI-549）的发现，其对其他脂质激酶和蛋白激酶的选择性超过100倍。IPI-549表现出良好的药代动力学特性，并能在体内强力抑制PI3K-γ介导的中性粒细胞迁移，目前正处于针对晚期实体瘤患者的1期临床评估阶段。
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