We next asked to what extent SIM1 might exhibit both avidity, i.e. enhanced binding affinity for BET proteins due to intramolecular BD1 and BD2 binding, and cooperativity within the ternary complex, i.e. enhanced affinity of forming ternary complex relative to the corresponding binary complex. We used established phage-based bromodomain displacement assays to quantitatively measure compound binding with tandem bromodomain constructs (Supplementary Information). Bidentate SIM1 showed picomolar affinity to tandem bromodomain constructs BRD2(1,2), BRD3(1,2), BRD4(1,2) and full-length BRD4, with 50-90X increase in affinity compared to monodentate (R,S)-SIM1 evidencing its avidity (Fig and