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CHR-6494 {[allProObj[0].p_purity_real_show]}

货号:A878417

CHR-6494 is a potent and selective Haspin (Haploid Germ Cell-Specific Nuclear Protein Kinase) inhibitor that blocks H3T3ph phosphorylation.

CHR-6494 化学结构 CAS号:1333377-65-3
CHR-6494 化学结构
CAS号:1333377-65-3
CHR-6494 3D分子结构
CAS号:1333377-65-3
CHR-6494 化学结构 CAS号:1333377-65-3
CHR-6494 3D分子结构 CAS号:1333377-65-3
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CHR-6494 纯度/质量文件 产品仅供科研

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CHR-6494 生物活性

描述 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 参考文献

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

[2]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.

[3]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.

CHR-6494 实验方案

计算器
存储液制备 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.42mL

0.68mL

0.34mL

17.10mL

3.42mL

1.71mL

34.21mL

6.84mL

3.42mL

CHR-6494 技术信息

CAS号1333377-65-3
分子式C16H16N6
分子量 292.338
别名
运输蓝冰
存储条件

液体 -20°C:3-6个月-80°C:12个月

粉末 Keep in dark place,Inert atmosphere,2-8°C

溶解度

DMSO: 50 mg/mL(171.03 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

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