EPZ5676

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.

1380288-87-8

EPZ5676 | EPZ-5676 | EPZ 5676 | Pinometostat

>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

C30H42N8O3

562.71

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.