Selectivity, ligand deconstruction, and cellular activity analysis of a BPTF bromodomain inhibitor.

ABSTRACT: Bromodomain and PHD finger containing protein transcription factor (BPTF) is an epigenetic protein involved in chromatin remodelling and is a potential anticancer target. The BPTF bromodomain has one reported small molecule inhibitor (AU1, rac-1). Here, advances made on the structure-activity relationship of a BPTF bromodomain ligand are reported using a combination of experimental and molecular dynamics simulations leading to the active enatiomer (S)-1. Additionally, a ligand deconstruction analysis was conducted to characterize important pharmacophores for engaging the BPTF bromodomain. These studies have been enabled by a protein-based fluorine NMR approach, highlighting the versatility of the method for selectivity, ligand deconstruction, and ligand binding. To enable future analysis o

SUBMITTER: Kirberger SE 

PROVIDER: S-EPMC6374164 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature