We chose to exemplify this approach using BRD4 as the target protein. While there is not an urgent need for the development of further BRD4 ligands, the availability of structural information on both BRD4 bromodomains make it an excellent testing ground for this technology. BRD4, together with BRD2, BRD3 and BRDT, comprise the BET family of bromodomain-containing proteins, which function as a readers of acetyl lysine (KAc) residues on histones, and other proteins. All members of the BET family are characterized by the presence of two bromodomains, BD1 and BD2, located at the N-terminus of the protein. Owing to the highly conserved nature of the members of the BET family, developing ligands that selective targeting the different isoforms, and between the two tandem domains, has been an important challenge and only relatively few highly selective ligands for the discrete domains have been reported to date. Our strategy potentially provides a rapid method to identify inhibitors that selectively inhibit protein domains with very similar sequences, for example BD1 over BD2, or vice versa.