Description

EPZ***6,CAS *********8
 

EPZ***6 is a potent inhibitor of DOT1L histone methyltransferase, according to Xray crystallographic analysis, that occupies the Sadenosyl methionine (SAM) binding pocket of DOT1L and induces conformational changes in DOT1L resulting in the opening of a hydrophobic pocket beyond the amino acid portion of SAM. EPZ***6 selectively inhibits DOTIL with a value of *0% inhibition concentration IC*0 of 0.8 nM, which is ****0fold greater in selectivity than other methyltransferases, including CARM1, EHMT1/2, EZH1/2, PRMT1/2/5/6/8, SETD7, SMYD2/3, and WHSC1/1L1. EPZ***6 has been investigated for the treatment of MLLrearranged leukemia in multiple studies where results have shown that EPZ***6 inhibits H3K*9 methylation and the expression of MLLfusion target gene and potently kills acute leukemia cell lines bearing MLL translocation.

Reference

Daigle SR, Olhava EJ, Therkelsen CA, Basavapathruni A, Jin L, BoriackSjodin PA, Allain CJ, Klaus CR, Raimondi A, Scott MP, Waters NJ, Chesworth R, Moyer MP, Copeland RA, Richon VM, Pollock RM. Potent inhibition of DOT1L as treatment of MLLfusion leukemia. Blood. ***3 Aug 8;**2(6):*******5.

(2R,3S,4S,5R)2(6aminopurin9yl)5[[[3[2(6tertbutyl1Hbenzimidazol2yl)ethyl]cyclobutyl]propan2ylamino]methyl]oxolane3,4diol