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.

聚梳抑制复合物2（PRC2）在组蛋白甲基化中起着重要作用-H3处的K27发生三甲基化，这是基因沉默的表观遗传学特征。据报道，抑制PRC2是治疗各种癌症的有前途的策略。在开发PRC2抑制剂方面已经做出了巨大的努力，其中一些已经进行了临床试验。这些抑制剂的结合方式是众所周知的。在这里，我们通过着重于它们的化学型，活性，选择性和结合模式来总结PRC2成分抑制剂在药物发现和开发方面的进展。我们相信，这种分析将通过建立基于结构的药物设计平台，为下一代PRC2抑制剂的设计和开发提供新的途径。