| abstract |
The present invention relates to the inhibition of wild type and certain mutant forms of human histone methyltransferase EZH2, which is 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 the mutant type of EZH2 such that trimethylation of H3-K27 associated with certain cancers is inhibited. The method can be used to treat cancer, including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods for identifying selective small molecule inhibitors of mutant forms of EZH2 and also for determining reactivity to EZH2 inhibitors in a subject. |