Identification of synthetic inhibitors for the DNA binding of intrinsically disordered circadian clock transcription factors. Issue 76 (2nd September 2020)

• Record Type: Journal Article
• Authors: Hosoya, Yusuke; Nojo, Wataru; Kii, Isao; Suzuki, Takanori; Imanishi, Miki; Ohkanda, Junko
• Is Part Of: Chemical communications. Volume 56:Issue 76(2020)
• Page Start: 11203
• Page End: 11206
• Publication Date: 2020-09-02
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d0cc04861e
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : Fluorescent-based library screening for the DNA-binding of disordered BMAL1 and CLOCK identified heterocyclic inhibitors which possess low micromolar activity. Abstract : Essential components of the human circadian clock, BMAL1 and CLOCK, which are intrinsically disordered transcription factors, were expressed and subjected to a fluorescent in vitro binding assay using an E-box DNA fragment. Screening of a chemical library identified 5, 8-quinoxalinedione (1 ), which was found to inhibit binding of the heterodimer BMAL1/CLOCK to E-box at low micromolar concentrations.