From Hit Seeking to Magic Bullets: The Successful Union of Epigenetic and Fragment Based Drug Discovery (EPIDD + FBDD)
In this review, we summarize the progress made over the past 15 years in applying fragment-based drug discovery (FBDD) to epigenetic drug discovery (EPIDD), with a focus on targeting epigenetic writer and eraser enzymes, as well as reader domains. The most notable successes have been in the identification of bromodomain-binding ligands. Through screening a diverse collection of fragment hits, several potent and selective compounds have been developed, including oncology clinical candidates such as mivebresib, ABBV-744, pelabresib, and PLX51107.