EPZ5676

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

EPZ-5676 是一种蛋白质甲基转移酶 DOT1L 的 S-腺苷甲硫氨酸 (SAM) 竞争性抑制剂，Ki 为 80 pM。

EPZ-5676 is an S-adenosyl methionine (SAM) competitive inhibitor of protein methyltransferase DOT1L with Ki of 80 pM, demonstrating >37,000-fold selectivity against all other PMTs tested, inhibits H3K79 methylation in tumor. Phase 1.(In Vitro):Pinometostat (EPZ-5676) inhibits H3K79me2 with IC50 values of 3 nM and 5 nM in MV4-11 and HL60 cells, respectively. Pinometostat (EPZ-5676) is a potent inhibitor of MV4-11 proliferation with an IC50 value of 3.5 nM. Pinometostat (EPZ-5676) induces a synergistic and durable antiproliferative effect, increases expression of differentiation markers and apoptosis as single agent, and demonstrates combination benefit in combination with AML standard of care drugs in MLL-r cells.(In Vivo):Pinometostat (EPZ-5676) (70 mg/kg, i.p.) causes complete and sustained regression in a rat xenograft model of MLL-rearranged leukemia. Pinometostat (EPZ-5676) (70, 35 mg/kg, i.v.) reduces HOXA9 and MEIS1 mRNA levels of tumors taken from rats, and reduces MLL-fusion target gene expression in vivo.

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EPZ5676 | EPZ-5676 | EPZ 5676 | Pinometostat

Chromatin/Epigenetic

HMTase

DOT1L

Cancer

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1380288-87-8

562.71

C30H42N8O3

>98% (HPLC)

Ethanol: 92 mg/mL warmed (163.49 mM); DMSO: 100 mg/mL warmed (177.71 mM)

O[C@H]1[C@H](N2C=NC3=C(N)N=CN=C23)O[C@H](CN([C@H]4C[C@@H](CCC5=NC6=CC(C(C)(C)C)=CC=C6N5)C4)C(C)C)[C@H]1O

(2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol

(-20℃)

With Ice Pack

≥ 2 years