Small-Molecule Inhibition of the Acyl-Lysine Reader ENL as a Strategy against Acute Myeloid Leukemia.
Yiman LiuQinglan LiFatemeh AlikaramiDeclan R BarrettLeila MahdaviHangpeng LiSylvia TangTanweer A KhanMayako MichinoConnor M HillLele SongLu YangYuanyuan LiSheela Pangeni PokharelAndrew W StamfordNigel LivertonLouis M RenzettiSimon J TaylorGillian F WattTammy LadduwahettyStacia KargmanPeter T MeinkeMichael A FoleyJunwei ShiHaitao LiMartin P CarrollChun-Wei David ChenAlessandro GardiniIvan P MaillardDavid J HugginsKathrin Maria BerntLiling WanPublished in: Cancer discovery (2022)
AML is a poor-prognosis disease for which new therapeutic approaches are desperately needed. We developed an orally bioavailable inhibitor of ENL, demonstrated its potent efficacy in MLL-rearranged and NPM1-mutated AML, and determined its mechanisms of action. These biological and chemical insights will facilitate both basic research and clinical translation. This article is highlighted in the In This Issue feature, p. 2483.