CHR-6494 TFA is a potent haspin inhibitor with an IC50 value of 2 nM. CHR-6494 TFA inhibits the phosphorylation of histone H3 threonine 3. CHR-6494 TFA induces apoptosis in cancer cells, such as melanoma and breast cancer. CHR-6494 TFA can be used in cancer research[1][2][3 ].CHR-6494 TFA dose-dependently inhibited the growth of HCT-116, HeLa, MDA-MB-231, and Wi-38 cancer cells with IC50 values of 500 nM, 473 nM, 752 nM, and 1059 nM, respectively, at a concentration range of <105 nM for 72 h. At a concentration of 500 nM, CHR-6494 TFA inhibited the growth of cancer cells with IC50 values of 500 nM, 473 nM, 752 nM, and 1059 nM, respectively. At a concentration of 500 nM, CHR-6494 TFA causes a mitotic catastrophe with abnormal morphology of the mitotic spindle and centrosome amplification, and up-regulates the spindle assembly checkpoint protein BUB1 and the mitotic arrest marker cytosolic protein B1[1].CHR-6494 TFA has inhibitory activity against melanoma cell lines, including BRAFV600E mutant, NRAS mutant and wild-type cells, with IC50 values ranging from 396 nM to 1229 nM. At 300 nM and 600 nM concentrations for 72 hours, CHR-6494 TFA induced apoptosis and increased caspase 3/7 activity to 3-fold and 6-fold, respectively, in COLO-792 cells, and to 8.5-fold and 16-fold, respectively, in RPMI-7951 melanoma cells[2].At the concentration of 50 and 200 nM for 1 week, CHR-6494 TFA enhanced the antiproliferative effect of MLN8237 in MDA-MB-231 and SKBR3 breast cancer cells, and increased apoptosis[3].
CHR-6494 TFA 动物研究
Animal study
At a dose of 50 mg/kg, administered intraperitoneally in two cycles of five consecutive days for 15 days, CHR-6494 TFA inhibited tumour growth in nude mice bearing HCT-116 human colorectal cancer cells[1].CHR-6494 TFA inhibited tumour growth in nude mice bearing MDA-MB-231 xenograft tumours when administered intraperitoneally at 20 mg/kg for 15 consecutive days[3].
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