The present invention relates to 1,4-disubstituted naphthalene scaffold compounds and other closely related scaffold compounds. The present invention also relates to combinatorial libraries of such compounds. In addition, the present invention relates to a method of identifying a protein-protein interaction antagonist. The method first involves providing a compound as described herein. Next, the compound is contacted with interacting proteins of a protein-protein interaction target complex, whereby the compound is allowed to compete with the interacting proteins. Then, the activity of the compound for inhibiting formation of the protein-protein interaction target complex is measured. Finally, the compound that inhibits formation of the protein-protein interaction target complex is identified as a protein-protein interaction antagonist. Also disclosed is a method for modulating a protein-protein interaction. The method involves contacting interacting proteins of a protein-protein interaction target with a compound as described herein, whereby the protein-protein interaction between the interacting proteins is modulated.