Eganelisib (IPI-549) is an inhibitor of PI3Kγ (IC50 = 16, 3,200, 3,500, and >8,400 nM for PI3Kγ, PI3Kα, PI3Kβ, and PI3Kδ, respectively)

PI3Kγ:16 nM

IPI-549使多柔比星耐药的SW620/Ad300细胞对P-糖蛋白(P-gp)底物敏感，例如紫杉醇（紫杉醇单独使用与联合IPI-549使用的IC50分别为710和6.7 nM），并提高了SW620/Ad300细胞内紫杉醇的水平[1]。

IPI-549 在体内展现出有益的药代动力学属性，并且对 PI3K-γ 介导的中性粒细胞迁移具有强效抑制作用[2]。

SW620 (4 X 10^6 ) and SW620/Ad300 (5 X 10^6 ) cells were injected subcutaneously at the flank near the armpits of athymic nude mice.?When the subcutaneous tumors were approximately 0.5 x 0.5 cm in size (day 0), the mice were randomized into four treatment groups.?The vehicle used to deliver the IPI-549 and paclitaxel by intraperitoneal (i.p.) injection was ethanol/Cremophor ELP/saline (10%/10%/80%).?Group one received the vehicle only;?group two received vehicle plus 3 mg/kg IPI-549;?group three received vehicle plus 15 mg/kg paclitaxel;?group four, the combination group, received vehicle plus 3 mg/kg IPI-549 one h prior to administration of vehicle plus 15 mg/kg paclitaxel.?The drug doses were administered every 3 days with a total of 4 doses.?Tumor volume was measured using calipers, and body weights were recorded prior to each dosing.