PF-05212384 (PKI-587)是一种高度有效的，双重PI3Kα， PI3Kγ和mTOR抑制剂，IC50分别为0.4 nM， 5.4 nM和1.6 nM。PKI-587有效作用于PI3Kα最常突变形式,尤其是H1047R和E545K，IC50分别为0.6 nM 和0.6 nM。与抑制PI3K/mTOR信号通路蛋白磷酸化相一致，PKI-587作用于MDA-361和PC3-MM2 细胞系，抑制肿瘤细胞生长，IC50分别为4 nM和13.1 nM。

>98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

Gedatolisib；PF-05212384

白色至类白色固体

DMSO ：3.1 mg/mL (5 mM) with gentle warming

PI3Kα ,mTOR ,PI3Kγ

PKI-587 shows potent inhibitory activity against PI3K-α, PI3K-γ and mTOR with IC50 of 0.4 nM, 5.4 nM and 1.6 nM, respectively. Furthermore, PKI-587 also exhibits its potency against the most frequently occurring mutant forms of PI3Kα, notably the H1047R and E545K with IC50 of 0.6 nM and 0.6 nM, respectively. Correlated with suppression of phosphorylation of PI3K/mTOR signaling pathway proteins, PKI-587 causes tumor cell growth inhibition in MDA-361 and PC3-MM2 cell lines with IC50 of 4 nM and 13.1 nM, respectively.

In nude mice, PKI-587 treatment at 25 mg/kg iv leads to low plasma clearance (7 (mL/min)/kg), high volume of distribution (7.2 L/kg), and long half-life, (14.4 hours). In the MDA-361 xenograft model, PKI-587 produces potent antitumor efficacy with the minimum efficacious dose (MED) of 3 mg/kg against MDA-361 tumors and maximum tolerated single dose (MTD) of 30 mg/kg. While in the H1975 (non-small-cell lung carcinoma, mutant EGFR ) xenograft model, PKI-587 at 25 mg/kg for 7 weeks results in 90% survival of the group treated.

PKI-587 and sorafenib targeting PI3K/AKT/mTOR and Ras/Raf/MAPK pathways synergistically inhibit HCC cell proliferation.
Gedaly R,et al. J Surg Res. 2012 Aug;176(2):542-8. PMID: