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

Yi Li, Zhiqing Liu, Galina Aglyamova, Jianping Chen, Haiying Chen, Mukund Bhandari, Mark A. White, Gabrielle Rudenko, Jia Zhou

Research output: Contribution to journalArticle

Abstract

The transcription factor ΔFosB 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 ΔFosB. Herein we describe the identification of a novel phenanthridine analogue ZL0220 (27) as an active and promising ΔFosB chemical probe with micromolar inhibitory activities against ΔFosB homodimers and ΔFosB/JunD heterodimers.

Original languageEnglish (US)
Article number127300
JournalBioorganic and Medicinal Chemistry Letters
Volume30
Issue number16
DOIs
StatePublished - Aug 15 2020

Keywords

  • Chemical probes
  • Fluorescence polarization assay
  • High-throughput screening
  • ΔFosB homodimer
  • ΔFosB/JunD heterodimer

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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