中文名称:

3-(1H-吲唑-5-基)-N-丙基咪唑并[1,2-B]哒嗪-6-胺

中文同义词:

3-(1H-吲唑-5-基)-N-丙基咪唑并[1,2-B]哒嗪-6-胺;单倍体生殖细胞特异性核蛋白激酶HASPIN抑制剂(CHR-6494)

英文名称:

CHR-6494

英文同义词:

3-(1H-indazol-5-yl)-N-propyliMidazo[1,2-b]pyridazin-6-aMine;CHR-6494 3-(1H-indazol-5-yl)-N-propyliMidazo[1,2-b]pyridazin-6-aMine;3-(1H-Indazol-5-yl)-N-propyl-imidazo[1,2-b]pyridazin-6-amine trifluoroacetate salt;3-(1H-Indazol-5-yl)-N-propylimidazo[1,2-b]pyridazin-6-amine trifluoroacetate salt;CHR 6494 trifluoroacetate salt;CHR-6494 trifluoroacetate salt;Haspin Kinase Inhibitor, CHR-6494;CHR-6494

CAS号:

1333377-65-3

分子式:

C16H16N6

分子量:

292.34

EINECS号:

相关类别:

细胞生物学试剂;细胞周期

Mol文件:

1333377-65-3.mol

密度 

1.39±0.1 g/cm3(Predicted)

储存条件 

2-8°C

溶解度 

DMSO: soluble5mg/mL, clear (warmed)

形态

powder

酸度系数(pKa)

13.24±0.40(Predicted)

颜色

white to beige

生物活性

CHR-6494 是一种有效的 haspin 抑制剂，能够抑制组蛋白 H3T3 的磷酸化，IC50 值为 2 nM。

靶点

IC50: 2 nM (haspin)

体外研究

CHR-6494 is a potent inhibitor of haspin, inhibiting histone H3T3 phosphorylation, with an IC 50 of 2 nM. CHR-6494 does not modify H3S10 and H328 phosphorylation levels, and shows no significantly inhibitory effects on other protein kinases such as Aurora B kinase. CHR-6494 dose-dependently inhibits the growth of cancer cells, such as HCT-116, HeLa, MDA-MB-231, and Wi-38 cell, with IC 50 s of 500 nM, 473 nM, 752 nM and 1059 nM, respectively. CHR-6494 (500 nM) produces a mitotic catastrophe with abnormal morphology of the mitotic spindle and centrosome amplification, and upregulates the spindle assembly checkpoint protein BUB1 and the marker of mitotic arrest cyclin B1. CHR-6494 exhibits inhibitory activities against melanoma cell lines, including BRAFV600E mutants, NRAS mutants, and wild type cells, with IC 50 s ranging from 396 nM to 1229 nM. CHR-6494 (300 nM and 600 nM) induces apoptosis, increases caspase 3/7 activity by 3- and 6-fold, respectively in COLO-792 cells, and to 8.5- and 16-fold in RPMI-7951 cells. CHR-6494 in combination with MEK inhibitors synergistically inhibits viability of melanoma cells, enhances apoptosis in melanoma cells, modulates cell cycle progression independently by arresting melanoma cells at different phases, and suppresses migration of melanoma cells.

体内研究

CHR-6494 (50 mg/kg, i.p.) inhibits the growth of tumor and cuases no obvious body weight change in nude mice bearing HCT-116 human colorectal cancer cells.

WGK Germany 

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