产品说明书

EPZ004777 HCl

Print
Chemical Structure| 1380316-03-9 同义名 : EPZ004777 hydrochloride
CAS号 : 1380316-03-9
货号 : A523386
分子式 : C28H42ClN7O4
纯度 : 98+%
分子量 : 576.131
MDL号 : N/A
存储条件：

粉末

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(182.25 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

H2O: 100 mg/mL(173.57 mM)，配合低频超声助溶
动物实验配方：
生物活性
描述 The DOT1L, a kind of H3K79 methyltransferase, is another important histone-methylation regulator. DOT1L plays a role in several processes such as mixed-lineage leukemia gene (MLL)-rearranged leukemia, erythropoiesis, cardiac differentiation, embryonic development, cartilage homeostasis and chondrocyte differentiation by inducing H3K79 methylation. EPZ004777 HCl is a potent, selective DOT1L inhibitor with an IC50 of 0.4 nM in a cell-free assay. In in vitro, studies have demonstrated that EPZ004777 leads to a dose-dependent reduction in the global H3K79 dimethylation level, and has highest selective binding ability with DOT1L than other HMTs, including PRMT5. Of note, EPZ004777 is strikingly susceptive for the MLL-rearranged cell lines, such as MLL-AF9, MLL-AF10 and CALM-AF10 genes transformed murine bone hematopoietic cells at a dose of 3 μM or more greater, resulting in the cell cycle arrest, growth inhibition, differentiation and apoptosis. The number of MV4-11 and MOLM-13 cells, MLL-rearranged cell lines, is dramatically reduced by EPZ004777, whereas the growth of Jurkat cells is unaffected, further supported its high specificity. In in vivo, EPZ004777 HCl effective suppressed tumor growth in MLL leukemia xenograft mice and improved life expectancy. Moreover, mice exposure to EPZ004777 HCl daily for continuous 14 days significantly increase the total leucocytes in blood, mainly resulted from an increase in lymphocytes, monocytes and neutrophils. EPZ004777 is well tolerated and no overt toxicity is observed from 50-100 mg/mL. EPZ004777 (50, 100, or 150 mg/mL) administration is well tolerated, and no significant weight loss is observed, together with no significant weight loss.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.74mL

0.35mL

0.17mL

8.68mL

1.74mL

0.87mL

17.36mL

3.47mL

1.74mL
参考文献

[1]Chen L, Deshpande AJ, et al. Abrogation of MLL-AF10 and CALM-AF10-mediated transformation through genetic inactivation or pharmacological inhibition of the H3K79 methyltransferase Dot1l. Leukemia. 2013 Apr;27(4):813-22.

[2]Daigle SR, Olhava EJ, et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell. 2011 Jul 12;20(1):53-65.