Structure-based-design studies, with the crystal structure of the HOXB1–PBX1/DNA transcription factor complex, were used to identify 1, 4-disubstituted naphthalenes as potential antagonists. An initial library of 32 analogs was synthesized, two of which were found to be more potent than the reported activity for a 12 amino acid peptide antagonist. Antagonists were also identified of the related BRN1/DNA and BRN2/DNA transcription ...