Figure 3:

Covalent fragment hits exhibit selective reactivity toward BRD4-BD2 relative to other BET bromodomains. Deconvoluted MS spectra of mixtures containing (A) BRD4-BD2, (B) BRD4-BD1, or (C) BRD3-BD2 after incubation with DMSO (black) or fragment 142 (red), 66 (blue), or 26 (grey). Since BRD4-BD1 and BRD3-BD2 together contain all three homologous BET bromodomain cysteine residues (highlighted in yellow in Figure 1A), these results suggest the three covalent fragment hits selectively react with one of the two BRD4 nonhomologous cysteine residues, Cys356 or Cys391 (Figure 1A).