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PF-03814735
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
PF-03814735图片
CAS NO:942487-16-3
包装:5mg, 10mg, 50mg
包装与价格:
包装价格(元)
5mg电议
10mg电议
50mg电议

产品介绍

生物活性

PF-03814735 is a novel, potent, orally bioavailable, reversible small-molecule Aurora kinase inhibitor with IC50 of 0.8, 5, 10 and 22 nM for Aurora 1, Aurora 2, Flt 1 and FAk, respectively. Aurora kinases are serine- threonine kinases that play essential roles in mitotic checkpoint control during mitosis. PF-03814735?possesses potential antineoplastic activity. Aurora kinase inhibitor PF-03814735 binds to and blocks Aurora kinases A and B, which may result in the prevention of cellular division and proliferation in tumor cells that overexpress these kinases. In intact cells, the preventive activity of PF-03814735 on the Aurora1 and Aurora2 kinases attenuates levels of phospho-Aurora1, phosphohistone H3, and phospho-Aurora2. PF-03814735 generates a block in cytokinesis, leading to prevention of cell proliferation and the formation of polyploid multinucleated cells. Although PF-03814735 generates significant prevention of several other protein kinases, the predominant biochemical effects in cellular assays are consistent with inhibition of Aurora kinases. Once-daily oral injection of PF-03814735 to mice bearing human xenograft tumors generates an attenuation in phosphohistone H3 in tumors at doses that are tolerable and that result in significant inhibition of tumor growth. The combination of PF-03814735 and docetaxel in xenograft mouse tumor models shows additive tumor growth inhibition. PF-03814735 is originally developed by Pfizer. The phase I clinical trials for the treatment of solid tumors has been completed.


化学数据

分子量474.48
分子式C23H25F3N6O2
CAS号942487-16-3
纯度>98%
溶解性(25°C)DMSO
储存和运输条件固体粉末: -20°C 冷藏长期储存
常温运输及临时存放

实验操作 来自于公开的文献,仅供相同实验参考(如实验材料、目的不同,请参考其他文献)

细胞实验
细胞系HCT-116 cell
方法Growing cell lines in appropriate media and evaluating after 48 h of exposure to either PF-03814735 or vehicle, followed by cell number determination in a Coulter Counter. Proliferation (as measured by an increase in cell number) is expressed as a percent of untreated controls. To evaluate the PF-03814735 exposure time required for antiproliferative activity, culturing HL-60 cell cultures in RPMI medium supplemented with 15% heat-inactivated fetal bovine serum and exposing them to various PF-03814735 concentrations for 4, 8, 12, 24, and 48 hours, followed by a washout step and incubation with growth media without PF-03814735 for the remainder of the 72-h assay period. Evaluating continuous exposure to PF-03814735 for 72 hours . Determining cell counts by a Coulter Counter.
浓度300 nM
处理时间4, 8, 12, 24, 48, or 72 hours

动物实验
动物模型HCT116 tumors are implanted s.c. on the right flank of nude mice.
配制PF-03814735 is formulated as a solution in cremophor EL [cremophor/ethanol/0.9% saline (12.5%/12.5%/75%)].
剂量10, 20, 30 mg/kg
给药处理Administered orally

不同实验动物依据体表面积的等效剂量转换表(数据来源于FDA指南)

小鼠大鼠豚鼠仓鼠
重量 (kg)0.020.151.80.40.0810
体表面积 (m2)0.0070.0250.150.050.020.5
Km系数36128520
动物 A (mg/kg) = 动物 B (mg/kg) × 动物 B的Km系数
动物 A的Km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Km系数(3),再除以大鼠的Km系数(6),得到化合物用于大鼠的等效剂量为10 mg/kg。


储备液配制

以下数据基于产品分子量,对于特殊产品,请参照COA中的储备液配制条件和说明进行操作。

Concentration / Solvent Volume / Mass1 mg5 mg10 mg
1 mM2.1076 mL10.5379 mL21.0757 mL
5 mM0.4215 mL2.1076 mL4.2151 mL
10 mM0.2108 mL1.0538 mL2.1076 mL