生物活性 EPZ004777 is a potent, selective DOT1L inhibitor with an IC50 of 0.4 nM.
IC50 & Target IC50: 0.4 nM (DOT1L)[1]
体外研究(In Vitro) EPZ004777 demonstrates potent, concentration-dependent inhibition of DOT1L enzyme activity with an IC50 of 400±100 pM. EPZ004777 displays remarkable selectivity for inhibition of DOT1L over other HMTs(PRMT5, 521±137 nM; others, >50 μM). The effect of extended EPZ004777 treatment is remarkably specific for the MLL-rearranged cell lines. The number of viable MV4-11 and MOLM-13 cells is dramatically reduced by EPZ004777, whereas the growth of Jurkat cells is unaffected. A small population of MV4-11 cells remain viable in the presence of EPZ004777, but their number remain constant when growth curves are tracked over longer periods indicating that they have ceased to divide. The proliferation of MLL-AF9-transformed cells is strongly inhibited by EPZ004777 at concentrations of 3 μM or greater[1]. EPZ004777 selectively inhibits proliferation of MLL-AF10 and CALM-AF10 transformed murine bone marrow cells[2].
体内研究(In Vivo) EPZ004777 is well tolerated and no overt toxicity is observed. Complete blood count analysis after 14 days of continuous exposure to EPZ004777 revealed a statistically significant increase in the total white blood cell count, which resulted from an increase in neutrophils, monocytes, and lymphocytes. EPZ004777 (50, 100, or 150 mg/mL) administration is well tolerated, and no significant weight loss is observed[1].
分子量 539.67
性状 Solid
Formula C28H41N7O4
CAS 号 1338466-77-5
运输条件 Room temperature in continental US; may vary elsewhere.
储存方式 Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month 溶解性数据 In Vitro: DMSO : 80 mg/mL (148.24 mM; Need ultrasonic)
配制储备液 浓度溶剂体积质量 1 mg 5 mg 10 mg 1 mM 1.8530 mL 9.2649 mL 18.5298 mL 5 mM 0.3706 mL 1.8530 mL 3.7060 mL 10 mM 0.1853 mL 0.9265 mL 1.8530 mL * 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂: