Paul Bamborough

TL;DR: X-ray crystal structures of compounds bound into bromodomains of Brd2 and Brd4 elucidate the molecular interactions of binding and explain the precisely defined stereochemistry required for activity.

TL;DR: This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.

TL;DR: A thorough characterization of the Published Kinase Inhibitor Set is provided and chemical starting points for designing new chemical probes of orphan kinases are identified and the utility of these leads are illustrated by developing a selective inhibitor for the previously untargeted kinases LOK and SLK.

TL;DR: It is found that steady-state gene expression primarily requires BD1, whereas the rapid increase of gene expression induced by inflammatory stimuli requires both BD1 and BD2 of all BET proteins, which may guide future BET-targeted therapies.

TL;DR: A pharmacological approach to validate whether substrates are phosphorylated by LRRK2 and use this to provide evidence that L RRK2 may not be rate-limiting for the phosphorylation of the proposed substrate moesin is described.