Polycomb repressive complex 2 inhibitors: emerging epigenetic modulators

Abstract

Polycomb repressive complex 2 (PRC2) plays a significant part in histone methylation - trimethylating K27 at H3, an epigenetic hallmark of gene silencing. Inhibition of PRC2 has been reported as a promising strategy for the treatment of various cancers. Significant efforts have been made toward the development of PRC2 inhibitors and some of them have progressed to clinical trials. The binding mode of these inhibitors is well understood. Here, we summarize the advances in drug discovery and development for PRC2 component inhibitors by focusing on their chemotypes, activity, selectivity and binding modes. We believe that such analysis will provide new avenues for the design and development of next-generation PRC2 inhibitors through establishment of a structure-based drug design platform.