Figure 2.

Binding affinity and cooperativity of ternary complex formation. A) Dose‐dependent displacement of a fluorescent HIF‐1α peptide by 1 alone or 1 in complex with a BET bromodomain, measured by fluorescence polarization. Cooperative binding is observed for all the BD2s while slightly negatively cooperative binding is observed for the BD1s. B) Representative inverse ITC titrations of VCB into 1 and VCB into 1:Brd2^BD1 or 1:Brd4^BD2 showing cooperative binding in the case of Brd4^BD2 and negatively cooperative binding in the case of Brd2^BD1.