Knowledge about interrelationships between different proteins is crucial in fundamental research for the elucidation of protein networks and pathways. Furthermore, it is especially critical in chemical biology to identify further key regulators of a disease and to take advantage of polypharmacology effects. Here, we present a new concept that combines a scaffold-based analysis of bioactivity data with a subsequent screening to identify novel inhibitors for a protein target of interest. The initial scaffold-based analysis revealed a flavone-like scaffold that can be found in ligands of different unrelated proteins indicating a similarity in ligand binding. This similarity was further investigated by testing compounds on bromodomain-containing protein 4 (BRD4) that were similar to known ligands of the other identified protein targets. Several new BRD4 inhibitors were identified and proven to be validated hits based on orthogonal assays and X-ray crystallography. The most important discovery was an unexpected relationship between BRD4 and peroxisome-proliferator activated receptor gamma (PPARγ). Both proteins share binding site similarities near a common hydrophobic subpocket which should allow the design of a polypharmacology-based ligand targeting both proteins. Such dual-BRD4-PPARγ modulators open up new therapeutic opportunities, because both are important drug targets for cancer therapy and many more important diseases. Thereon, a complex structure of sulfasalazine was obtained that involves two bromodomains and could be a potential starting point for the design of a bivalent BRD4 inhibitor.