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KW 2449

现货
Catalog No.
A4123
多重激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 880.00
现货
10mg
¥ 650.00
现货
50mg
¥ 2,600.00
现货
200mg
¥ 7,100.00
现货

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Background

KW 2449 is a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase with IC50 values of 6.6nM, 14nM, 4nM and 48nM, respectively [1].

KW-2449 is a potent kinase inhibitor against FLT3, ABL, T315I-mutant ABL (ABL-T315I) tyrosine kinases as well as Aurora kinase. In vitro assay shows KW-2449 has the potency of growth inhibition with different mechanisms. In leukemia cells with FLT3 mutations, KW-2449 down-regulates phosphorylated-FLT3/STAT5, induces G1 arrest and apoptosis. KW-2449 also inhibits tumor growth in FLT3-mutated xenograft model. While in leukemia cells with wild-type FLT3, KW-2449 reduces phosphorylated histone H3, induces G2/M arrest and apoptosis. However, it is reported that the AML patients treated with LT3 inhibitors, such as KW-2449, have only partial FLT3 inhibition in vivo. And the plasma level of FL (the ligand of FLT3) appears to rise after chemotherapy, which impeding the efficacy of the FLT3 inhibitors [1, 2].

References:
[1] Shiotsu Y, Kiyoi H, Ishikawa Y, Tanizaki R, Shimizu M, Umehara H, Ishii K, Mori Y, Ozeki K, Minami Y, Abe A, Maeda H, Akiyama T, Kanda Y, Sato Y, Akinaga S, Naoe T. KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.
[2] Sato T, Yang X, Knapper S, White P, Smith BD, Galkin S, Small D, Burnett A, Levis M. FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivo. Blood. 2011 Mar 24;117(12):3286-93.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt332.4
Cas No.1000669-72-6
FormulaC20H20N4O
Solubility≥16.6 mg/mL in DMSO, <2.25 mg/mL in EtOH, <2.39 mg/mL in H2O
Chemical Name[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone
SDFDownload SDF
Canonical SMILESC1CN(CCN1)C(=O)C2=CC=C(C=C2)C=CC3=NNC4=CC=CC=C43
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

MOLM-13细胞

溶解方法

在DMSO中的溶解度>16.6mg/mL。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

0.01-0.3 μM; 24, 48和72 h; 37°C

应用

在MOLM-13细胞中,KW-2449以剂量依赖的方式抑制FLT3(P-FLT3)的磷酸化及其下游分子磷酸化STAT5(P-STAT5)。此外,KW-2449增加了G1期细胞的百分比,降低了S期细胞的百分比,导致细胞凋亡增加。

动物实验[1]:

动物模型

携带皮下MOLM-13肿瘤的SCID小鼠

剂量

2.5, 5.0, 10和20 mg/kg; 口服; 每天2次,给药14天

应用

在携带皮下MOLM-13肿瘤的SCID小鼠中,KW-2449从4到12小时完全降低肿瘤中P-FLT3和P-STAT5的水平。虽然FLT3和STAT5的磷酸化在24小时恢复到几乎基础水平。KW-2449以剂量依赖的方式表现出有效和显著的抗肿瘤作用。

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] Shiotsu Y, Kiyoi H, Ishikawa Y, Tanizaki R, Shimizu M, Umehara H, Ishii K, Mori Y, Ozeki K, Minami Y, Abe A, Maeda H, Akiyama T, Kanda Y, Sato Y, Akinaga S, Naoe T. KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.

生物活性

描述 KW 2449是多重激酶FLT3、ABL、Aurora激酶和FGFR的抑制剂。
靶点 FLT3 FLT3 (D835Y) Abl Abl (T315I) Aurora A FGFR1
IC50 6.6 nM 1 nM 14 nM 4 nM 48 nM 36 nM

质量控制