中文名 | CHR-6494 |
英文名 | CHR-6494 |
别名 | 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) |
英文别名 | CHR-6494 CHR 6494 trifluoroacetate salt CHR-6494 trifluoroacetate salt Haspin Kinase Inhibitor, CHR-6494 3-(1H-indazol-5-yl)-N-propyliMidazo[1,2-b]pyridazin-6-aMine 3-(1H-Indazol-5-yl)-N-propylimidazo[1,2-b]pyridazin-6-amine trifluoroacetate salt 3-(1H-Indazol-5-yl)-N-propyl-imidazo[1,2-b]pyridazin-6-amine trifluoroacetate salt CHR-6494 3-(1H-indazol-5-yl)-N-propyliMidazo[1,2-b]pyridazin-6-aMine |
CAS | 1333377-65-3 |
化学式 | C16H16N6 |
分子量 | 292.34 |
密度 | 1.39±0.1 g/cm3(Predicted) |
溶解度 | DMSO: 可溶5mg/mL,澄清 (温热) |
酸度系数 | 13.24±0.40(Predicted) |
存储条件 | 2-8°C |
外观 | 粉末 |
颜色 | white to beige |
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 | 3 |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 3.421 ml | 17.103 ml | 34.207 ml |
5 mM | 0.684 ml | 3.421 ml | 6.841 ml |
10 mM | 0.342 ml | 1.71 ml | 3.421 ml |
5 mM | 0.068 ml | 0.342 ml | 0.684 ml |
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