| abstract |
The present invention relates to human EZH2 inhibitors and methods of application thereof, in particular to the inhibition of wild-type and certain mutant forms of human histone methyltransferase EZH2, which is a catalytic subunit of a PRC2 complex that complexes It catalyzes the mono- to tri-methylation of lysine 27 (H3-K27) on histone H3. In one embodiment, the inhibition is selective for the mutant form of EZH2, thereby inhibiting the trimethylation of H3-K27 associated with certain cancers. The methods can be used to treat cancers, including follicular lymphoma and diffuse large B-cell lymphoma (DLBCL). The present invention also provides methods for identifying small molecule selective inhibitors of mutant forms of EZH2, and methods for determining responsiveness to EZH2 inhibitors in a subject. |