Kevin Lee

TL;DR: A synthetic compound (I-BET) is described that by ‘mimicking’ acetylated histones disrupts chromatin complexes responsible for the expression of key inflammatory genes in activated macrophages, and confers protection against lipopolysaccharide-induced endotoxic shock and bacteria-induced sepsis.

TL;DR: It is shown that a novel small molecule inhibitor of the BET family, GSK1210151A (I-BET151), has profound efficacy against human and murine MLL-fusion leukaemic cell lines, through the induction of early cell cycle arrest and apoptosis, establishing the displacement of BET proteins from chromatin as a promising epigenetic therapy for these aggressive leukaemias.

TL;DR: The assay is developed to identify a ligand for the orphan receptor GPR1, suggesting a role for this receptor in the regulation of inflammation and an experimental strategy to monitor protein interactions in a cell with a high degree of selectivity and sensitivity.

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: The main phenotypic consequence of BET inhibition in MLL fusion leukaemia is a dramatic early induction of cell cycle arrest and apoptosis and a novel class of potent small molecule inhibitors to the BET family, which is chemically distinct to previously published BET-inhibitors are developed.