Holly H. Soutter

TL;DR: Crystal structures of PAR2 in complex with two distinct antagonists and a blocking antibody provide a basis for the development of selective PAR2 antagonists for a range of therapeutic uses.

TL;DR: The medicinal chemistry effort featured the judicious placement of lipophilicity, informed by co-crystal structures with IRAK4 and optimization of ADME properties to deliver clinical candidate PF-06650833 (compound 40), which displays a 5-unit increase in lipophilic efficiency from the fragment hit, excellent kinase selectivity, and pharmacokinetic properties suitable for oral administration.

TL;DR: This study is the first fragment‐based crystallographic screen against HIV PR, and the first time that fragments were screened against an inhibitor‐bound drug target to search for compounds that both bind to novel sites and stabilize the inhibited conformation of the target.

TL;DR: A DNA-encoded library screen is reported leading to the discovery of BAY-850, a potent and isoform selective inhibitor that specifically induces ATAD2 bromodomain dimerization and prevents interactions with acetylated histones in vitro, as well as with chromatin in cells.

TL;DR: Imidazo[1,5-a]quinoxalines were synthesized that function as irreversible Bruton's tyrosine kinase (BTK) inhibitors that showed good in vivo efficacy in preclinical RA models and in complex with a gate-keeper variant of ITK enzyme.