EPZ5676  1380288-87-8

  EPZ-5676
分子式：C30H42N8O3   分子量：562.71
 
產(chǎn)品描述
EPZ-5676是蛋白甲基轉(zhuǎn)移酶 DOT1L的S-腺苷甲硫氨酸(SAM) 競(jìng)爭(zhēng)性抑制劑，Ki為80 pM,比作用于所有其他PMTs選擇性高37,000以上，抑制腫瘤H3K79甲基化。
靶點(diǎn)
DOT11L
         
IC50
80 pM Ki
         
體外研究
EPZ-5676 reduces H3K79 dimethylation with a cellular IC50 of 2.6 nM in MV4-11 cells. EPZ-5676 treatment results in concentration- and time-dependent reduction of H3K79 methylation without effect on the methylation status of other histone sites, which leads to inhibition of key MLL target genes and selective, apoptotic cell killing in MLL-rearranged leukemia cells. EPZ-5676 inhibits proliferation of MLL-AF4 rearranged cell line MV4-11 with an IC50 of 9 nM.
體內(nèi)研究
EPZ-5676 continuously intravenous infusion for 21 days to xenograft model of MLL-rearranged leukemia, leads to dose-dependent anti-tumor activity. At the highest dose of 70.5 mg/kg/day, complete tumor regressions are achieved with no regrowth for up to 32 days after the cessation of treatment. No significant weight loss or obvious toxicity is observed in rats treated with EPZ-5676 during efficacy study.
溶解性
DMSO 100 mg/mL，水 <1 mg/mL，乙醇 100 mg/mL
穩(wěn)定性
2年 -20°C粉狀，6月-80°C溶于DMSO