tcsc1419 Pinometostat

Pinometostat (EPZ-5676) is a potent DOT1L histone methyltransferase inhibitor with a K_i of 80 pM.

IC50 & Target: Ki: < 80 pM (DOT1L histone methyltransferase)

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^[1]. Pinometostat (EPZ-5676) induces a synergistic and durable antiproliferative effect, increases expression of differentiation markers and apoptosis as dingle agent, and demonstrates combination benefit in combination with AML standard of care drugs in MLL-r cells^[2].

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^[1].