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PF-03814735

现货
Catalog No.
A4128
Aurora A/B抑制剂
组合的产品项目
规格价格库存 数量
5mg
¥ 1,100.00
现货
10mg
¥ 1,900.00
Ship with 10-15 days
50mg
¥ 5,900.00
Ship with 10-15 days
200mg
¥ 14,900.00
Ship with 10-15 days

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Background

PF-03814735 is a potent, orally bioavailable, reversible inhibitor of both Aurora1 and Aurora2 kinases with IC50 values of 0.8nM and 5nM, respectively [1].

PF-03814735 is an ATP competitive inhibitor of Aurora kinases. It also shows inhibition of other protein kinases at 100nM, such as Flt1, FAK, TrkA, Met, and FGFR1. The immunofluorescence imaging analysis shows PF-03814735 can inhibit the phosphorylation of Aurora1, Aurora 2 as well as histone H3 in MDA-MB-231 cells. This inhibition is rapid and reversible. The inhibition of phosphorylated histone H3 also occurs in athymic mice bearing HCT-116 xenografts. PF-03814735 induces the formation of polyploid cells and multinucleated cells due to the block in cytokinesis secondary. Moreover, PF-03814735 treatment results in a reduction of cell proliferation in vitro (such as HL-60, A549, and H125) and a inhibition of tumor growth in vivo (human xenograft mouse models, such as A2780 ovarian carcinoma and HCT-116) [1].

References:
[1] Jani JP, Arcari J, Bernardo V, Bhattacharya SK, Briere D, Cohen BD, Coleman K, Christensen JG, Emerson EO, Jakowski A, Hook K, Los G, Moyer JD, Pruimboom-Brees I, Pustilnik L, Rossi AM, Steyn SJ, Su C, Tsaparikos K, Wishka D, Yoon K, Jakubczak JL. PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. Mol Cancer Ther. 2010 Apr;9(4):883-94.

Chemical Properties

Physical AppearanceA crystalline solid
StorageStore at -20°C
M.Wt474.48
Cas No.942487-16-3
FormulaC23H25F3N6O2
SolubilitySoluble in DMSO
SDFDownload SDF
Canonical SMILESCC(=O)NCC(=O)N1C2CCC1C3=C2C=CC(=C3)NC4=NC=C(C(=N4)NC5CCC5)C(F)(F)F
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1]:

细胞系

MDA-MB-231细胞,各种肿瘤类型(HCT-116,HL-60,A549和H125)以及大鼠(C6)、小鼠(L1210)和狗(MDCK)起源的肿瘤细胞系。

溶解方法

该化合物在DMSO中的溶解度> 10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

1-1000 nM; 4, 8, 12, 24和48 h

应用

在MDA-MB-231细胞中,PF-03814735显著降低Aurora1 Thr 232上的磷酸化和组蛋白H3 Ser10上磷酸化,IC50值为20nmol / L和50nmol / L。在各种肿瘤细胞系中,PF-03814735导致细胞数减少,IC50值范围为42至150nmol / L。300nmol / L的PF-03814735近乎完全抑制细胞增殖。

动物实验[1]:

动物模型

皮下移植HCT-116人结肠直肠癌异种移植物的无胸腺小鼠

剂量

10, 20和30 mg/kg; 口服给药,10天

应用

在皮下移植HCT-116人结肠直肠癌异种移植物的无胸腺小鼠中,与对照相比,PF-03814735(≥20mg/ kg)导致≥50%的统计学显著和剂量依赖性的肿瘤生长抑制。肿瘤生长抑制与磷酸化组蛋白H3水平的降低相关,每天约5小时有≥50%的降低,持续10天。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

[1] Jani JP, Arcari J, Bernardo V, Bhattacharya SK, Briere D, Cohen BD, Coleman K, Christensen JG, Emerson EO, Jakowski A, Hook K, Los G, Moyer JD, Pruimboom-Brees I, Pustilnik L, Rossi AM, Steyn SJ, Su C, Tsaparikos K, Wishka D, Yoon K, Jakubczak JL. PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. Mol Cancer Ther. 2010 Apr;9(4):883-94.

生物活性

Description PF-03814735是一种新型有效的和可逆的Aurora A和B抑制剂,IC50值分别为20 nM和150 nM。
靶点 Aurora A Aurora B        
IC50 20 nM 150 nM        

质量控制

质量控制和MSDS

批次:

化学结构

PF-03814735