PF-4989216

目录号: HY-13864

PI3K/Akt/mTOR-

PF-4989216是一种新型有效的选择性PI3K抑制剂, PF-4989216抑制PI3Kalpha (Ki=0.6 nM) 和mTOR (Ki=1440 nM)。

PI3K

相关产品

LY294002-3-Methyladenine-Wortmannin-BYL-719-BEZ235-NVP-BKM120-CAL-101-IPI549-SAR405-GDC-0941-TGR-1202-LY3023414-Quercetin-Vps34-IN-1-BAY 80-6946-

生物活性

Description

PF-4989216 is a novel potent and selective PI3K inhibitor. PF-4989216 inhibits PI3Kalpha (Ki=0.6 nM) and mTOR (Ki=1440 nM).IC50 value: 0.6 nM (Ki, PI3Kalpha), 1440 nM (Ki, mTOR) [1]Target: PI3Kin vitro: PF-4989216inhibits pAKT-S473 with IC50 of 79 nM. [1] PF-4989216 is a potent inhibitor of pan-PI3K isoforms and demonstrates excellent selectivity when screened against more than 100 kinases and 50 non-kinases. PF-4989216 is significantly more potent in SCLCs with PIK3CA mutations than wild-type lines, including cells with PIK3CA copy number gain, providing evidence that SCLCs harboring PIK3CA mutations are more sensitive to inhibition by PF-4989216. [2]vivo: PF-4989216 exhibits good exposure in mice after oral administration and the unbound drug concentration increased with dose, with the ability to maintain approximately 700, 1,900, and 2,100 nM at the 7-hour time point at dosages of 50, 150, and 350 mg/kg, respectively. [2]

References

[1].Liu KK, et al. Highly Selective and Potent Thiophenes as PI3K Inhibitors with Oral Antitumor Activity. ACS Med Chem Lett. 2011 Sep 19;2(11):809-813.

[2].Walls M, et al. Targeting small cell lung cancer harboring PIK3CA mutation with a selective oral PI3K inhibitor PF-4989216. Clin Cancer Res. 2014 Feb 1;20(3):631-643.