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。
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.