PF-04691502

目录号 M1984 所有产品仅供科研使用，严禁用于人或动物的治疗等任何其他用途，不为任何个人提供产品和服务

PF-04691502是一种ATP竞争性的PI3K(α/β/δ/γ)/mTOR双重抑制剂，K_i为1.8 nM/2.1 nM/1.6 nM/1.9 nM和16 nM，对Vps34， AKT， PDK1， p70S6K， MEK， ERK， p38和JNK几乎没有作用活性。

规格	价格	库存状态
Free Sample (0.5-1 mg)	¥ 0	中国库存现货
5mg	¥ 600	中国库存现货
10mg	¥ 850	中国库存现货
25mg	¥ 1750	中国库存现货
50mg	¥ 3000	中国库存现货

其他规格数量报价？

质量标准及产品资料

纯度： 98.68%
COA
MSDS
H-NMR
LC/MS

产品信息

生物活性

使用AbMole产品发表的文献

Mol Ther Nucleic Acids. 2016 Nov 15;5(11):e384.

Enhanced Anticancer Activity of PF-04691502, a Dual PI3K/mTOR Inhibitor, in Combination With VEGF siRNA Against Non–small-cell Lung Cancer

产品使用成果展示

	数据来源	Mol Ther Nucleic Acids.(2016). PF-04691502, Figure 7. (Abmole Bioscience, Houston, TX)
	方法
	细胞系/动物模型	A549 and H460 cell
	浓度	5 nmol/l to 5 µmol/l for A549, and 5 nmol/l to 100 µmol/l for H460 cells
	处理时间	72 h
	实验结果	In A549 cells PF0 and siRNA-V combination revealed a moderate synergism at 6 and 12 nmol/l siRNA-V concentration, and slight synergism at 18 nmol/l, with CI values between 0.62 and 0.88 (Figure 7a, Table 1). In H460 cells, PF0 and siRNA-V showed moderate synergism at 4 nmol/l siRNA-V concentration, synergism at 6 nmol/l, and slight synergism at 12 nmol/l, with CI values between 0.51 and 0.81 (Figure 7b, Table 1).

	数据来源	Mol Ther Nucleic Acids.(2016). PF-04691502, Figure 6. (Abmole Bioscience, Houston, TX)
	方法	tube formation assays
	细胞系/动物模型	human umbilical vein endothelial cells (HUVEC)
	浓度	100 nmol/l
	处理时间	6 h
	实验结果	PF0 treatment showed poor organization of HUVEC tube-like structures and a nonsignificant (P < 0.05) decrease in segments length (75.63 ± 13.71%) compared to control (Figure 6e).

	数据来源	Mol Ther Nucleic Acids.(2016). PF-04691502, Figure 5. (Abmole Bioscience, Houston, TX)
	方法	wound healing assay
	细胞系/动物模型	A549 and H460 cell
	浓度
	处理时间
	实验结果	A549 and H460 cells also showed significant (P < 0.05) differences between PF0 (200 nmol/l for A549 and 2,000 nmol/l for H460) treated and nontreated cells (Figure 5c,d). A549 cells showed that after 16 hours of 50 nmol/l siRNA-V and 200 nmol/l PF0 treatment wound closure was 18.48 ± 1.60% comparing with 47.24 ± 2.09 of the control treated cells.

	数据来源	Mol Ther Nucleic Acids.(2016). PF-04691502, Figure 4. (Abmole Bioscience, Houston, TX)
	方法	Inhibition of anchorage-dependent colony formation
	细胞系/动物模型	A549 and H460 cells
	浓度	200 nmol/l for A549 and 2,000 nmol/l for H460
	处理时间
	实验结果	The reduction was more remarkable after PF0 was combined with siRNA-V showing a significant (P < 0.05) decrease in colony formation to a 29.83 ± 8.11% as compared with control. For A549 cells, the combination resulted in a significant (P < 0.05) colony formation reduction when compared with PF0 treatment (Figure 4c). The relative colony-forming ability of H460 cells was reduced after PF0 treatment to 61.86 ± 20.48% and after siRNA-V treatment to 73.21 ± 1.97% as compared with controls (Figure 4b,d). PF0 and siRNA-V combination showed a significant (P < 0.05) decrease in relative colony formation to 7.97 ± 9.20% as compared with control groups.

	数据来源	Mol Ther Nucleic Acids.(2016). PF-04691502, Figure 3. (Abmole Bioscience, Houston, TX)
	方法	VEGF silencing effect analysis by quantitative real-time PCR
	细胞系/动物模型	A549 and H460 cells
	浓度	200 nmol/l for A549 and 2,000 nmol/l for H460
	处理时间	48 h
	实验结果	In A549 cells, the siRNA-V treatment showed a significant (P < 0.05) decrease of 62.58 ± 16.60% in VEGF gene expression compared to control (Figure 3a). siRNAV and PF0 combination treatment showed a significantly (P < 0.01) decreased VEGF expression of 75.06 ± 13.21% compared to control. In H460 cells, we observed a significant (P < 0.001) decrease in the relative VEGF mRNA expression after siRNA-V transfection by 92.22 ± 3.10% as well as after the combination treatment 69.59 ± 7.71% compared to control cells (Figure 3b).

	数据来源	Mol Ther Nucleic Acids.(2016). PF-04691502, Figure 2. (Abmole Bioscience, Houston, TX)
	方法	siRNA-V and PF0 combination cytotoxicity assays
	细胞系/动物模型	A549, H460 cells
	浓度	5 to 500 nmol/l for A549, and 10 to 5,000 nmol/l for H460 cells
	处理时间	24, 48, and 72 h
	实验结果	We observed a significant (P < 0.05) decrease in relative cell viability for the combination compared to singleagent treatments (Figure 2a,b). The combination cytotoxicity assays demonstrated that siRNA-V potentiates the anticancer activity of PF0 against A459 and H460 cells.

	数据来源	Mol Ther Nucleic Acids.(2016). PF-04691502, Figure 1. (Abmole Bioscience, Houston, TX)
	方法	Dose response cytotoxicity analysis
	细胞系/动物模型	A549 cells
	浓度	5 to 5,000 nmol/l
	处理时间	24, 48, and 72 h
	实验结果	In H460 cells, PF0 (5 nmol/l to 200 µmol/l) or siRNA-V (5 to 200 nmol/l) cytotoxicity was also found to be dose and time dependent (Figure 1d,e and Supplementary Figure S2). IC50 values for PF0 in H460 cells were 1,965.5 ± 131.7 nmol/l; 1,080.1 ± 307.1 nmol/l; 936.7 ± 174.6 nmol/l after 24, 48, and 72 hours of treatment respectively (Figure 1d and Supplementary Figure S2a).

实验参考

体外实验*
细胞系	BT20, U87MG, and SKOV3 cells
方法	Cell proliferation assays. BT20, U87MG, and SKOV3 cells were plated at 3,000 cell/well in 96-well culture plates in growth medium with 10% FBS. Cells were incubated overnight and treated with DMSO (0.1% final) or serial diluted compound for 3 days. Resazurin was added to 0.1 mg/mL. Plates were incubated at 37°C in 5% CO2 for 3 hours. Fluorescence signals were read as emission at 590 nm after excitation at 530 nm. IC50 values were calculated by plotting fluorescence intensity to drug concentration in nonlinear curves.
浓度	0~1000 nM
处理时间	3 days

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

体内实验*
动物模型	SKOV3, U87MG, or NSCLC cells tumour xenograft models in Female nu/nu mice (6–8 weeks old)
配制	0.5% methylcellulose in water suspension
剂量	0.5, 1, 5, and 10 mg/kg once daily
给药处理	orally

*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。

化学性质

分子量	425.48
分子式	C22H27N5O4
CAS号	1013101-36-4
溶解性（25°C）	DMSO 13 mg/mL
储存条件	粉末型式 -20°C 3年；4°C 2年溶于溶剂 -80°C 6个月；-20°C 1个月
运输方式	冰袋运输，根据产品的不同，可能会有相应调整。

储备液配制

*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	2.3503 mL	11.7514 mL	23.5029 mL
5 mM	0.4701 mL	2.3503 mL	4.7006 mL
10 mM	0.235 mL	1.1751 mL	2.3503 mL

不同实验动物依据体表面积的等效剂量转换表（参考来源于公开文献）

	小鼠	大鼠	兔	豚鼠	仓鼠	狗
重量 (kg)	0.02	0.15	1.8	0.4	0.08	10
体表面积 (m²)	0.007	0.025	0.15	0.05	0.02	0.5
K_m 系数	3	6	12	8	5	20

动物 A (mg/kg) = 动物 B (mg/kg) ×	动物 B的K_m系数
	动物 A的K_m系数

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

参考文献

[1] Yuan J, et al. Mol Cancer Ther. PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activity.

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