A transcription factor hijacking to regulate RARα by using a chimeric molecule of retinoic acid and a DNA alkylator.

As a model compound for the transcription factor hijacking mechanism of action of DNA damaging agent that simultaneously bind to the nuclear receptor, we designed and synthesized a chimeric molecule, RA-mustard, which can bind with both retinoic acid receptor α (RARα) and DNA. The interaction between RA-mustard with RARα was confirmed by binding assay using RARα-overexpressing cell extract. RA-mustard-modified DNA diminished the RARα-dependent luciferase expression in the RARα-abundant cells.