PF-477736

目录号 M1764 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-477736是一种有效的，选择性，ATP竞争性Chk1(check point kinase 1)抑制剂，K_i为0.49 nM，也抑制VEGFR2， Aurora-A， FGFR3， Flt3， Fms (CSF1R)， Ret和Yes。作用于Chk1比作用于Chk2选择性高100倍左右。

别名：PF-0044736

规格	价格	库存状态
Free Sample (0.5-1 mg)	¥ 0	中国库存现货
10mM*1mL in DMSO	¥ 855	中国库存现货
2mg	¥ 459	中国库存现货
5mg	¥ 846	中国库存现货
10mg	¥ 1440	中国库存现货
50mg	¥ 4095	中国库存现货
100mg	¥ 6210	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： 99.21%
COA
MSDS
H-NMR
HPLC

产品信息

生物活性

PF-477736是一种有效的，选择性，ATP竞争性Chk1抑制剂，K_i为0.49 nM，也抑制VEGFR2， Aurora-A， FGFR3， Flt3， Fms (CSF1R)， Ret和Yes。作用于Chk1比作用于Chk2选择性高100倍左右。PF 477736(128 nM)作用于CA46 和 HeLa细胞，废除Camptothecin诱导的DNA损伤检查点，这种作用具有剂量依赖性。PF 477736作用于HT29细胞，有效废除Gemcitabine诱导的S期停滞，使凋亡细胞群相应增加。PF 477736(540 nM)作用于HT29细胞，增强Gemcitabine诱导的细胞毒性,这种作用具有时间和剂量依赖性。

使用AbMole产品发表的文献

Mol Cancer Res. 2022 Mar 1;20(3):456-467.

Chk1 Inhibition Potently Blocks STAT3 Tyrosine705 Phosphorylation, DNA-Binding Activity, and Activation of Downstream Targets in Human Multiple Myeloma Cells
Sci Rep. 2017 Nov 14;7(1):15511.

Targeting a non-oncogene addiction to the ATR/CHK1 axis for the treatment of small cell lung cancer

产品使用成果展示

	数据来源	Sci Rep (2017). Figure 6. PF-477736 (Abmole Bioscience)
	方法	i.p.
	细胞系/动物模型	Xenograft mouse model
	浓度	20 mg/kg
	处理时间	1–5 day
	实验结果	While vehicle-treated xenograft tumors derived from H-82 (Fig. 6D), H-526 (Fig. 6E) and H-69 (Fig. 6F) cells displayed a rapid growth, both VE-822 and PF-477736 treatment led to a massively delayed tumor growth in all three models, which was mimicked by a substantial reduction in Ki67 staining on histological examination in tumors that were excised following completion of treatment (Fig. 6G,H).

	数据来源	Sci Rep (2017). Figure 5. PF-477736 (Abmole Bioscience)
	方法	i.p.
	细胞系/动物模型	Xenograft mouse model
	浓度	20 mg/kg
	处理时间	1–5 day
	实验结果	While tumors displayed continuous growth in vehicle-treated animals, all tumors in the PF-477736-exposed cohort displayed a substantial volume reduction after completion of the second cycle

	数据来源	Sci Rep (2017). Figure 4. PF-477736 (Abmole Bioscience)
	方法	i.p.
	细胞系/动物模型	Xenograft mouse model
	浓度	20 mg/kg
	处理时间	1–5 day
	实验结果	Contrary to these substantial therapeutic effects inflicted by VE-822 and PF-477736 in SCLC-bearing animals, we only observed a minute survival extension in VE-822- and PF-477736-treated NSCLC-bearing mice.

	数据来源	Sci Rep (2017). Figure 3. PF-477736 (Abmole Bioscience)
	方法	Immunofluorescence
	细胞系/动物模型	SCLC and NSCLC cells
	浓度	1.0 μM
	处理时间	48 h
	实验结果	Fully in line with our immunofluorescence data, SCLC cell lines displayed a significantly stronger γH2AX signal following VE-822 and PF-477736 treatment, than their NSCLC counterparts

	数据来源	Sci Rep (2017). Figure 2. PF-477736 (Abmole Bioscience)
	方法	Flow cytometry
	细胞系/动物模型	SCLC and NSCLC cell
	浓度	0.1 μM, 1.0 μM, 3.0 μM
	处理时间	48 h
	实验结果	Of note, the slow growing cell line RP2 was less sensitive to VE-822 and PF-477736, compared to cell lines RP1, 3 and 4. The rapidly proliferating SCLC cell line RP5 displayed the most pronounced sensitivity to the cell cycle checkpoint abrogating agents VE-822 and PF-477736.

实验参考

体外实验*
细胞系	p53-defective human cancer cell lines HT29 cells
方法	IC50 MTT. The proliferation assays were done using an MTT assay. The IC50 assay measures the antiproliferative effects of PF-00477736 on p53-defective human cancer cell lines. Cells in each line were seeded in complete medium at an exponentially growing density in 96-well assay plate and allowed to attach for 16 h. Serial dilutions of PF-00477736 were then done, and appropriate controls were added to each plate. Cells were incubated with drug for 96 h. After incubation, MTT working stock diluted in complete medium was added to each well, and cells were incubated for 4 h. After centrifugation and supernatant removal, DMSO was added to each well and plates were read on SpectraMax plate reader at 540 nm. IC50 and PF50 results were calculated by concentration-response curve fitting using a Microsoft Excel–based four-variable analysis method.
浓度	0, 180, 360 and 540 n M
处理时间	96 h

*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	Colo205 cells tumour Xenograft Models in Athymic Nude Mice
配制	50 nM sodium acetate buffer and 4% dextrose (pH 4)
剂量	4-60 mg/kg q3d × 4
给药处理	i.p.

*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	419.48
分子式	C22H25N7O2
CAS号	952021-60-2
溶解性（25°C）	DMSO 40 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	2.3839 mL	11.9195 mL	23.839 mL
5 mM	0.4768 mL	2.3839 mL	4.7678 mL
10 mM	0.2384 mL	1.192 mL	2.3839 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] Zhang C, et al. Clin Cancer Res. PF-00477736 mediates checkpoint kinase 1 signaling pathway and potentiates docetaxel-induced efficacy in xenografts.

[2] Blasina A et al. Mol Cancer Ther. Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1.

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