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 catalyzes monomethylation to trimethylation of lysine 27 (H3-K27) on histone H3. . In one embodiment, the inhibition is selective for the mutant form of EZH2, whereby trimethylation of H3-K27, which is associated with certain cancers, is inhibited. The method can be used to treat cancers, including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). Also provided are methods of identifying small molecule selective inhibitors of mutant forms of EZH2, and methods of determining reactivity to EZH2 inhibitors in a subject. |