ZM-447439 是一种强效、选择性的 Aurora 激酶抑制剂,能够与 Aurora 激酶的活性位点结合,将 Aurora 激酶锁定在非活性构象中,从而阻断其在细胞有丝分裂过程中的关键作用。ZM-447439 通过诱导细胞周期停滞和凋亡,在 Hep2癌细胞等多种癌症的三维培养模型中显示出显著的抗癌潜力。
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产品名称 | Aurora A ↓ ↑ | Aurora B ↓ ↑ | Aurora C ↓ ↑ | 其他靶点 | 纯度 | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
BI-847325 |
++
Aurora A (Human), IC50: 25 nM |
++++
Aurora B (Xenopus laevis), IC50: 3 nM |
++
Aurora C (Human), IC50: 15 nM |
99%+ | |||||||||||||||
CCT 137690 |
++
Aurora A, IC50: 15 nM |
++
Aurora B, IC50: 25 nM |
++
Aurora C, IC50: 19 nM |
99%+ | |||||||||||||||
MK-5108 |
++++
Aurora A, IC50: 0.064 nM |
99%+ | |||||||||||||||||
KW-2449 |
+
Aurora A, IC50: 48 nM |
FLT3 | 99%+ | ||||||||||||||||
Tozasertib |
++++
Aurora A, Ki app: 0.6 nM |
++
Aurora B, Ki app: 18 nM |
+++
Aurora C, Ki app: 4.6 nM |
FLT3,Bcr-Abl | 99%+ | ||||||||||||||
AT9283 |
++++
Aurora A, IC50: ~3.0 nM |
++++
Aurora B, IC50: ~3.0 nM |
99%+ | ||||||||||||||||
MLN8054 |
+++
Aurora A, IC50: 4 nM |
+
Aurora B, IC50: 172 nM |
99%+ | ||||||||||||||||
ZM-447439 |
+
Aurora A, IC50: 110 nM |
+
Aurora B, IC50: 130 nM |
Src | 99%+ | |||||||||||||||
TCS7010 |
++++
Aurora A, IC50: 3.4 nM |
99%+ | |||||||||||||||||
TAK-901 |
++
Aurora A-TPX2, IC50: 21 nM |
++
Aurora B-INCENP, IC50: 15 nM |
99%+ | ||||||||||||||||
Danusertib |
+++
Aurora A, IC50: 13 nM |
+
Aurora B, IC50: 79 nM |
+
Aurora C, IC50: 61 nM |
RET | 99%+ | ||||||||||||||
MK-8745 |
++++
Aurora A, IC50: 0.6 nM |
99+% | |||||||||||||||||
PHA-680632 |
++
Aurora A, IC50: 27 nM |
+
Aurora B, IC50: 135 nM |
+
Aurora C, IC50: 120 nM |
FLT3 | 99%+ | ||||||||||||||
AMG 900 |
+++
Aurora A, IC50: 5 nM |
+++
Aurora B, IC50: 4 nM |
++++
Aurora C, IC50: 1 nM |
99%+ | |||||||||||||||
Alisertib |
++++
Aurora A, IC50: 1.2 nM |
99%+ | |||||||||||||||||
ENMD-2076 |
+++
Aurora A, IC50: 14 nM |
+
Aurora B, IC50: 350 nM |
FLT3,RET | 98% | |||||||||||||||
JNJ-7706621 |
+++
Aurora A, IC50: 11 nM |
++
Aurora B, IC50: 15 nM |
99%+ | ||||||||||||||||
CYC-116 |
+++
Aurora A, Ki: 8 nM |
+++
Aurora B, Ki: 9 nM |
FLT3 | 99%+ | |||||||||||||||
Reversine |
+++
Aurora A, IC50: 12 nM |
+++
Aurora B, IC50: 13 nM |
++
Aurora C, IC50: 20 nM |
98% | |||||||||||||||
CCT129202 |
++
Aurora A, IC50: 42 nM |
+
Aurora B, IC50: 198 nM |
+
Aurora C, IC50: 227 nM |
98% | |||||||||||||||
SNS-314 mesylate |
+++
Aurora A, IC50: 9 nM |
++
Aurora B, IC50: 31 nM |
++++
Aurora C, IC50: 3 nM |
99%+ | |||||||||||||||
Barasertib-HQPA |
++++
Aurora B, IC50: 0.37 nM |
99%+ | |||||||||||||||||
Hesperadin |
+
Aurora B (human), IC50: 250 nM |
98% | |||||||||||||||||
GSK-1070916 |
++++
Aurora B-INCENP, IC50: 3.5 nM |
+++
Aurora C-INCENP, IC50: 6.5 nM |
SIK,Tie-2 | 99% | |||||||||||||||
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。 |
靶点 |
|
描述 | Cells treated with ZM-447439 enter interphase, proceed normally into mitosis, and assemble bipolar spindles. However, chromosome alignment, segregation, and cytokinesis all fail. ZM-447439 inhibits cell division and the mitotic phosphorylation of histone H3. It prevents chromosome alignment and separation, impairs spindle checkpoint function, and inhibits the kinetochore localization of BubR1, Mad2, and Cenp-E[1]. The inhibition of Aurora kinases by ZM-447439 reduces the phosphorylation of Ser10 on histone H3 in Hep2 cancer cells. Cells treated with ZM-447439 that are arrested in G2/M phase induce multipolar spindles and accumulate 4N/8N DNA, similar to cells with genetic suppression of Aurora-B. Treatment with ZM-447439 can induce apoptosis. The inhibition of Aurora kinases by ZM-447439 is closely associated with a reduction in the phosphorylation of Akt Ser473 and its substrates GSK3α/β Ser21 and Ser9[2]. |
细胞系 | 浓度 | 检测类型 | 检测时间 | 活动说明 | 数据源 |
human A172 cell | Growth inhibition assay | Inhibition of human A172 cell growth in a cell viability assay, IC50=0.98411 μM | SANGER | ||
human A498 cell | Growth inhibition assay | Inhibition of human A498 cell growth in a cell viability assay, IC50=2.3669 μM | SANGER | ||
human ABC-1 cell | Growth inhibition assay | Inhibition of human ABC-1 cell growth in a cell viability assay, IC50=1.40352 μM | SANGER | ||
human BE-13 cell | Growth inhibition assay | Inhibition of human BE-13 cell growth in a cell viability assay, IC50=0.84418 μM | SANGER | ||
Dose | Mice: 80 mg/kg[3] (i.p.) |
Administration | i.p. |
计算器 | ||||
存储液制备 | 1mg | 5mg | 10mg | |
1 mM 5 mM 10 mM |
1.95mL 0.39mL 0.19mL |
9.74mL 1.95mL 0.97mL |
19.47mL 3.89mL 1.95mL |
CAS号 | 331771-20-1 |
分子式 | C29H31N5O4 |
分子量 | 513.588 |
别名 | |
运输 | 蓝冰 |
存储条件 |
液体 -20°C:3-6个月-80°C:12个月 粉末 Sealed in dry,Store in freezer, under -20°C |
溶解度 |
DMSO: 25 mg/mL(48.68 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO |
动物实验配方 |