abstract |
The present invention relates to the inhibition of wild-type and specific mutant forms of human histone methyltransferase EZH2, a catalytic subunit of the PRC2 complex that promotes monomethylation to trimethylation of lysine 27 (H3-K27) on histone H3. In one embodiment, the inhibition is selective for a mutant form of EZH2, such that trimethylation of H3-K27 associated with a particular cancer is inhibited. The methods can be used to treat cancers, including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). In addition, a method for identifying a mutant form of a selective small molecule inhibitor of EZH2 and a method for determining reactivity to an EZH2 inhibitor in a subject are also provided. |