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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Li, Yi¹  Liu, Zhiqing¹  Aglyamova, Galina¹  Chen, Jianping¹  Chen, Haiying¹  Bhandari, Mukund¹  White, Mark A.^2,3  Rudenko, Gabrielle^1,3  Zhou, Jia^1,3 

[1] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA

[2] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA

[3] Univ Texas Med Branch, Sealy Ctr Struct Biol & Mol Biophys, Galveston, TX 77555 USA

关键词: Delta FosB homodimer;    Delta FosB/JunD heterodimer;    Chemical probes;    High-throughput screening;    Fluorescence polarization assay;   

DOI  :  10.1016/j.bmcl.2020.127300

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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