Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

TRIM24 is a transcriptional regulator as well as an E3 ubiquitin ligase. It is overexpressed in diverse tumors, and high expression levels have been linked to poor prognosis in breast cancer patients. TRIM24 contains a PHD/bromodomain offering the opportunity to develop protein interaction inhibitors that target this protein interaction module. Here we identified potent acetyl-lysine mimetic benzimidazolones TRIM24 bromodomain inhibitors. The best compound of this series is a selective BRPF1B/TRIM24 dual inhibitor that bound with a KD of 137 and 222 nM, respectively, but exerted good selectivity over other bromodomains. Cellular activity of the inhibitor was demonstrated using FRAP assays as well as cell viability data.

Original publication

DOI

10.1021/acs.jmedchem.5b00458

Type

Journal article

Journal

J Med Chem

Publication Date

25/02/2016

Volume

59

Pages

1642 - 1647

Keywords

Adaptor Proteins, Signal Transducing, Benzimidazoles, Carrier Proteins, Cell Line, Tumor, Crystallography, X-Ray, Humans, Lysine, Models, Molecular, Molecular Docking Simulation, Nuclear Proteins, Protein Structure, Tertiary