Lu Quinn, Quinn Amy M, Patel Mehul P, Semus Simon F, Graves Alan P, Bandyopadhyay Deepak, Pope Andrew J, Thrall Sara H
GlaxoSmithKline, Collegeville, Pennsylvania, USA.
J Biomol Screen. 2012 Jun;17(5):555-71. doi: 10.1177/1087057112437763. Epub 2012 Mar 5.
Epigenetic gene regulation is a critical process controlling differentiation and development, the malfunction of which may underpin a variety of diseases. In this article, we review the current landscape of small-molecule epigenetic modulators including drugs on the market, key compounds in clinical trials, and chemical probes being used in epigenetic mechanistic studies. Hit identification strategies for the discovery of small-molecule epigenetic modulators are summarized with respect to writers, erasers, and readers of histone marks. Perspectives are provided on opportunities for new hit discovery approaches, some of which may define the next generation of therapeutic intervention strategies for epigenetic processes.
表观遗传基因调控是控制细胞分化和发育的关键过程，其功能失调可能是多种疾病的基础。在本文中，我们综述了小分子表观遗传调节剂的现状，包括已上市药物、临床试验中的关键化合物以及用于表观遗传机制研究的化学探针。针对组蛋白修饰的写入者、擦除者和读取者，总结了发现小分子表观遗传调节剂的活性分子识别策略。我们还展望了新的活性分子发现方法的机遇，其中一些方法可能会定义下一代表观遗传过程的治疗干预策略。
