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.

CHR-6494 (0-10^-5 nM; 72 hours) dose-dependently inhibits the growth of cancer cells, such as HCT-116, HeLa, MDA-MB-231, and Wi-38 cells, with IC₅₀s 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 IC₅₀s ranging from 396 nM to 1229 nM.
CHR-6494 (300 nM and 600 nM; 72 hours) 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.
CHR-6494 (50, 200 nM; 1 week) enhances the antiproliferative effects of MLN8237 in MDA-MB-231, SKBR3 breast cancer cells.
CHR-6494 (200 nM; 72 hours) enhances the apoptosis of MDA-MB-231 and SKBR3 cells when combined with MLN8237.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

CHR-6494 (50 mg/kg; i.p. in two cycles of five consecutive days for 15 days) inhibits the growth of tumor and cuases no obvious body weight change in nude mice bearing HCT-116 human colorectal cancer cells.
CHR-6494 (20 mg/kg; intraperitoneal injection for 15 consecutive days) inhibits the tumor volume and weight compared with the control group in nude mice bearing MDA-MB-231 xenograft tumors.
CHR-6494 (20 mg/kg; intraperitoneal injection for 15 consecutive days) enhances the tumor volume and weight inhibition of MLN8237 (20 mg/kg; p.o.) in vivo.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

CHR-6494 (50 mg/kg; i.p. in two cycles of five consecutive days for 15 days) inhibits the growth of tumor and cuases no obvious body weight change in nude mice bearing HCT-116 human colorectal cancer cells.
CHR-6494 (20 mg/kg; intraperitoneal injection for 15 consecutive days) inhibits the tumor volume and weight compared with the control group in nude mice bearing MDA-MB-231 xenograft tumors.
CHR-6494 (20 mg/kg; intraperitoneal injection for 15 consecutive days) enhances the tumor volume and weight inhibition of MLN8237 (20 mg/kg; p.o.) in vivo.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Huertas D, et al. Antitumor activity of a small-molecule inhibitor of the histone kinase Haspin. Oncogene. 2012 Mar 15;31(11):1408-18.  [Content Brief]

  . Han L, et al. Anti-Melanoma Activities of Haspin Inhibitor CHR-6494 Deployed as a Single Agent or in a Synergistic Combination with MEK Inhibitor. J Cancer. 2017 Aug 25;8(15):2933-2943.  [Content Brief]

  . Chen A, et al. CRISPR/Cas9 screening identifies a kinetochore-microtubule dependent mechanism for Aurora-A inhibitor resistance in breast cancer. Cancer Commun (Lond). 2021 Feb;41(2):121-139.  [Content Brief]