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

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.

journal_name

Bioorg Med Chem Lett

authors

Li Y,Liu Z,Aglyamova G,Chen J,Chen H,Bhandari M,White MA,Rudenko G,Zhou J

doi

10.1016/j.bmcl.2020.127300

subject

Has Abstract

pub_date

2020-08-15 00:00:00

pages

127300

issue

16

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(20)30411-X

journal_volume

30

pub_type

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