Discovery of phenanthridine analogues as novel chemical probes disrupting the binding of DNA to ΔFosB homodimers and ΔFosB/JunD heterodimers

The transcription factor Delta FosB accumulates in response to chronic insults such as drugs of abuse, L-3,4-dihydroxyphenylalanine (L-DOPA) or stress in specific regions of the brain, triggering long lasting neural and behavioral changes that underlie aspects of drug addiction, dyskinesia, and depression. Thus, small molecule chemical probes are urgently needed to investigate biological functions of Delta FosB. Herein we describe the identification of a novel phenanthridine analogue ZL0220 (27) as an active and promising Delta FosB chemical probe with micromolar inhibitory activities against Delta FosB homodimers and Delta FosB/JunD heterodimers.