Paul V. Fish

TL;DR: The key protein families that mediate epigenetic signalling through the acetylation and methylation of histones are reviewed, including histone deacetylases, protein methyltransferases, lysine demethylases, bromodomain-containing proteins and proteins that bind to methylated histones.

TL;DR: A large number of compounds with low solubility have been developed in the past few years for use in drug discovery and drug development, and these include polymethine-like compounds, which have shown promise in the treatment of cancer.

TL;DR: A potent and highly selective dihydroquinazoline-2-one inhibitor, PFI-1, which efficiently blocks the interaction of BET BRDs with acetylated histone tails, and has antiproliferative effects on leukemic cell lines and efficiently abrogates their clonogenic growth.

TL;DR: The discovery and structure–activity relationship (SAR) of a novel, small-molecule chemical probe for BET family inhibition that was identified through the application of structure-based fragment assessment and optimization techniques has yielded a potent, selective compound with cell-based activity (PFI-1) that may further add to the understanding of BET family function within the bromodomains.

TL;DR: The discovery of (R)-PFI-2 is reported—a first-in-class, potent, highly selective, and cell-active inhibitor of the methyltransferase activity of human SETD7—and its 500-fold less active enantiomer, (S)-P FI-2.