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 细胞实验
Cell Line
Concentration
Treated Time
Description
References
U2OS cells
600 nM
28 h
To study the effect of CHR-6494 on the cell cycle of U2OS cells, results showed that CHR-6494 delayed the entry of cells into mitosis.
J Cell Physiol. 2020 May;235(5):4508-4519
HeLa cells
300 nM
15 h
To study the effect of CHR-6494 on the cell cycle of HeLa cells, results showed that CHR-6494 delayed the entry of cells into mitosis.
J Cell Physiol. 2020 May;235(5):4508-4519
MDA-MB-231 cells
500 nM
48 h
CHR-6494 inhibits H3T3 phosphorylation, leading to G2/M arrest and subsequent apoptosis
Oncogene. 2012 Mar 15;31(11):1408-18
HCT-116 cells
500 nM
48 h
CHR-6494 inhibits H3T3 phosphorylation, leading to G2/M arrest and subsequent apoptosis
Oncogene. 2012 Mar 15;31(11):1408-18
HeLa cells
500 nM
48 h
CHR-6494 inhibits H3T3 phosphorylation, leading to G2/M arrest and subsequent apoptosis
Oncogene. 2012 Mar 15;31(11):1408-18
MCF7 cells
200 nmol/L
96 h
To evaluate the effect of CHR-6494 on MLN8237 sensitivity, results showed that CHR-6494 significantly enhanced the killing effect of MLN8237.
Cancer Commun (Lond). 2021 Feb;41(2):121-139
SKBR3 cells
200 nmol/L
72 h
To evaluate the effect of CHR-6494 on MLN8237 sensitivity, results showed that CHR-6494 significantly enhanced the killing effect of MLN8237.
Cancer Commun (Lond). 2021 Feb;41(2):121-139
MDA-MB-231 cells
200 nmol/L
72 h
To evaluate the effect of CHR-6494 on MLN8237 sensitivity, results showed that CHR-6494 significantly enhanced the killing effect of MLN8237.
Cancer Commun (Lond). 2021 Feb;41(2):121-139
CHR-6494 TFA 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
HCT-116 human colorectal cancer xenograft model
Intraperitoneal injection
50 mg/kg
Once daily for 5 consecutive days, total 15 days
CHR-6494 showed antitumor activity without observed toxicity
Oncogene. 2012 Mar 15;31(11):1408-18
Nude mice
MDA-MB-231 xenograft model
Oral and intraperitoneal injection
20 mg/kg
Once daily for 15 consecutive days
To evaluate the antitumor effect of CHR-6494 in combination with MLN8237, results showed that the combination treatment significantly inhibited tumor growth.
Cancer Commun (Lond). 2021 Feb;41(2):121-139
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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