CHR-6494 is a potent inhibitor of haspin, with an IC50 of 2 nM. CHR-6494 inhibits histone H3T3 phosphorylation. CHR-6494 can be used in the research of cancer[1].
体内研究
Administration of CHR-6494 at doses of 50 mg/kg intraperitoneally in two cycles of five consecutive days for 15 days inhibits tumor growth without causing significant changes in body weight in nude mice bearing HCT-116 human colorectal cancer cells [1].
Moreover, CHR-6494 at a dose of 20 mg/kg via intraperitoneal injection for 15 consecutive days inhibits tumor volume and weight compared to the control group in nude mice bearing MDA-MB-231 xenograft tumors [3].
Additionally, CHR-6494 at a dose of 20 mg/kg via intraperitoneal injection for 15 consecutive days enhances the inhibition of tumor volume and weight when combined with MLN8237 (20 mg/kg orally) in vivo[3].
体外研究
Treatment with CHR-6494 at concentrations ranging from 0 to 500 nM for 72 hours results in a dose-dependent inhibition of cancer cell growth, including HCT-116, HeLa, MDA-MB-231, and Wi-38 cells, with IC50s of 500 nM, 473 nM, 752 nM, and 1059 nM, respectively [1].
At a concentration of 500 nM, CHR-6494 induces mitotic catastrophe characterized by abnormal morphology of the mitotic spindle and centrosome amplification. It also upregulates the spindle assembly checkpoint protein BUB1 and the mitotic arrest marker cyclin B1 [1].
Moreover, CHR-6494 exhibits inhibitory activities against melanoma cell lines, including BRAFV600E mutants, NRAS mutants, and wild-type cells, with IC50s ranging from 396 nM to 1229 nM [2].
Treatment with CHR-6494 at concentrations of 300 nM and 600 nM for 72 hours induces apoptosis, increasing caspase 3/7 activity by 3- and 6-fold, respectively, in COLO-792 cells and by 8.5- and 16-fold in RPMI-7951 cells [2].
Furthermore, CHR-6494 synergistically enhances the viability inhibition and apoptosis induction of melanoma cells in combination with MEK inhibitors. It also modulates cell cycle progression independently by arresting melanoma cells at different phases and suppresses melanoma cell migration [2].
Treatment with CHR-6494 at the concentration of 50- 200 nM for 1 week enhances the antiproliferative effects of MLN8237 in MDA-MB-231, SKBR3 breast cancer cells[3].
Treatment with CHR-6494 at the concentration of 50- 200 nM for 72 hours enhances the apoptosis of MDA-MB-231 and SKBR3 cells when combined with MLN8237[3].
CHR-6494 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MDA-MB-435
611 nM
72 h
CHR-6494 alone inhibits cell viability and induces apoptosis
J Cancer. 2017 Aug 25;8(15):2933-2943
MeWo
396 nM
72 h
CHR-6494 alone inhibits cell viability and induces apoptosis
J Cancer. 2017 Aug 25;8(15):2933-2943
RPMI-7951
628 nM
72 h
CHR-6494 alone inhibits cell viability and induces apoptosis
J Cancer. 2017 Aug 25;8(15):2933-2943
COLO-792
497 nM
72 h
CHR-6494 alone inhibits cell viability and induces apoptosis
J Cancer. 2017 Aug 25;8(15):2933-2943
U2OS cells
600 nM
28 h
To investigate the effect of CHR-6494 on the cell cycle of U2OS cells, results showed that CHR-6494 dose-dependently delayed the entry of cells into mitosis.
J Cell Physiol. 2020 May;235(5):4508-4519
HeLa cells
300 nM
15 h
To investigate 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
HK-2 cells
6.56 ± 0.02 µM
48 h
Evaluate the inhibitory effect of CHR-6494 on HK-2 cell proliferation
Pharmaceuticals (Basel). 2024 Oct 23;17(11):1420
NRK-49F cells
3.07 ± 0.32 µM
48 h
Evaluate the inhibitory effect of CHR-6494 on NRK-49F cell proliferation
Pharmaceuticals (Basel). 2024 Oct 23;17(11):1420
MDA-MB-231 cells
500 nM
48 h
CHR-6494 inhibits H3T3 phosphorylation, leading to G2/M cell cycle arrest and 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 cell cycle arrest and apoptosis
Oncogene. 2012 Mar 15;31(11):1408-18
HeLa cells
500 nM
48 h
CHR-6494 inhibits H3T3 phosphorylation, leading to G2/M cell cycle arrest and apoptosis
Oncogene. 2012 Mar 15;31(11):1408-18
SKBR3
200 nmol/L
72 h
To evaluate the synergistic therapeutic effects of CHR-6494 with MLN8237, results showed that CHR-6494 significantly enhanced the killing effects of MLN8237 on breast cancer cells.
Cancer Commun (Lond). 2021 Feb;41(2):121-139
MDA-MB-231
200 nmol/L
72 h
To evaluate the synergistic therapeutic effects of CHR-6494 with MLN8237, results showed that CHR-6494 significantly enhanced the killing effects of MLN8237 on breast cancer cells.
Cancer Commun (Lond). 2021 Feb;41(2):121-139
CHR-6494 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 significantly inhibits tumor growth without toxicity
Oncogene. 2012 Mar 15;31(11):1408-18
Nude mice
MDA-MB-231 xenograft model
Oral and intraperitoneal injection
20 mg/kg
15 consecutive days
To evaluate the synergistic antitumor effects of CHR-6494 with MLN8237 in vivo, results showed that the combination treatment significantly inhibited tumor growth.
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