New paper: Refinement of the “Bump-and-Hole” Approach to Allele-Selective BET Bromodomain Inhibition now published in Chemical Science

  • ToC graphics
  • Fig. 1 Bump-&-hole system optimization.
  • Fig. 2 L/V mutant characterization.
  • Scheme 1 Bumped compound synthesis.
  • Fig. 3 Compound modifications & BRD:ligand co-crystal structures.
  •  Fig. 4 Bumped compounds can inhibit single bromodomains and are effective in cells.
  • Fig. 5 Enantiomer Characterization.
  • Fig. 6 (2R,3S)-7: a potent and highly-selective bumped BET inhibitor.
  • Fig. 7 (2R,3S)-7 does not perturb WT BET-dependent cells.
  • Fig. 8 Application of the bump-&-hole system to a biological question.
  • Fig. 9 BRD4 and NF-κB-target gene expression.

Well done for this tour-de-force study to our BBSRC EastBio PhD student Andrew, to Kwok-Ho, Andrea, and to former Lab members Michael, Lars and Matt -with important contributions from our collaborators too!