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PF-04691502

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Chemical Structure| 1013101-36-4 同义名 : PF4691502
CAS号 : 1013101-36-4
货号 : A300869
分子式 : C22H27N5O4
纯度 : 98+%
分子量 : 425.481
MDL号 : MFCD18782794
存储条件：

粉末 Keep in dark place,Sealed in dry,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(117.51 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • p110γ

    PI3Kγ, Ki:1.9 nM

  • p110β

    PI3Kβ, Ki:2.1 nM

  • p110α

    PI3Kα, Ki:1.8 nM

  • p110δ

    PI3Kδ, Ki:1.6 nM
描述 The phosphoinositide 3-kinase (PI3K) signaling pathway plays a central role in regulating cell growth, proliferation, survival, angiogenesis, metabolism, and motility. PF-04691502 is an ATP-competitive PI3K/mTOR dual inhibitor, which potently inhibited recombinant class I PI3K and mTOR in biochemical assays and suppressed transformation of avian fibroblasts mediated by wild-type PI3K γ, δ, or mutant PI3Kα. Dual PI3K/mTOR inhibitors may most effectively block the PI3K pathway, overcome feedback loops, and block PI3K-independent mTOR activation. PF-04691502 inhibited human and mouse PI3Kα with Ki of 1.8 and 1.2 nmol/L, respectively, PI3K isoforms β, δ, and γ with Ki of 2.1, 1.6, and 1.9 nmol/L, respectively, and human mTOR with Ki of 16 nmol/L. PF-04691502 inhibited phosphorylation of AKT at S473 and T308 consistent with the inhibition of phosphorylation of AKT downstream proteins such as FKHRL1 and PRAS40. In PIK3CA-mutant and PTEN-deleted cancer cell lines, PF-04691502 reduced phosphorylation of AKT T308 and AKT S473 (IC50 of 7.5 – 47 nmol/L and 3.8 – 20 nmol/L, respectively) and inhibited cell proliferation (IC50 of 179 – 313 nmol/L). PF-04691502 inhibited mTORC1 activity in cells as measured by PI3K-independent nutrient stimulated assay, with an IC50 of 32 nmol/L and inhibited the activation of PI3K and mTOR downstream effectors including AKT, FKHRL1, PRAS40, p70S6K, 4EBP1, and S6RP. In a vivo study, PF-04691502 was formulated in 0.5% methylcellulose in water suspension, nude mice bearing U87MG tumors were administered orally once a day with PF-04691502 at 0.5, 1, 5, and 10 mg/kg. Dose-dependent tumor growth inhibition (TGI) was obtained in the U87MG xenograft model and approximately 73% TGI was observed at the MTD dose of 10 mg/kg[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human BT20 cells Function assay Inhibition of AKT phosphorylation at Ser 473 in human BT20 cells, IC50=0.013 μM 23506825
human SKOV3 cells Proliferation assay 3 days Antiproliferative activity against human SKOV3 cells after 3 days by CellTiter-Glo assay, IC50=0.29 μM 25139570
human U87MG cells Proliferation assay 4 days Antiproliferative activity against human U87MG cells after 4 days by CellTiter-Glo assay, IC50=0.52 μM 25139570
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.35mL

0.47mL

0.24mL

11.75mL

2.35mL

1.18mL

23.50mL

4.70mL

2.35mL
参考文献

[1]Simmons BH, Lee JH, et al. Combination of a MEK inhibitor at sub-MTD with a PI3K/mTOR inhibitor significantly suppresses growth of lung adenocarcinoma tumors in Kras(G12D-LSL) mice. Cancer Chemother Pharmacol. 2012 Aug;70(2):213-20.

[2]Kinross KM, Brown DV, et al. In vivo activity of combined PI3K/mTOR and MEK inhibition in a Kras(G12D);Pten deletion mouse model of ovarian cancer. Mol Cancer Ther. 2011 Aug;10(8):1440-9.

[3]Yuan J, Mehta PP, Yin MJ, Sun S, Zou A, Chen J, Rafidi K, Feng Z, Nickel J, Engebretsen J, Hallin J, Blasina A, Zhang E, Nguyen L, Sun M, Vogt PK, McHarg A, Cheng H, Christensen JG, Kan JL, Bagrodia S. PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activity. Mol Cancer Ther. 2011 Nov;10(11):2189-99. doi: 10.1158/1535-7163.MCT-11-0185. Epub 2011 Jul 12. PMID: 21750219.