A novel BPTF inhibitor scaffold Sanguinarine chloride was discovered via HTRF screening.

The binding mode of the Sanguinarine chloride was predicted through Molecular docking.

NMR, MST and SPR demonstrated the high binding affinity of Sanguinarine chloride to BPTF bromodomain.

Sanguinarine chloride displayed a potent anti-proliferative effect.

Chromatin remodeling regulates many basic cellular processes, such as gene transcription, DNA repair, and programmed cell death. As the largest member of nucleosome remodeling factor (NURF), BPTF plays a vital role in the occurrence and development of cancer. Currently, BPTF bromodomain inhibitors are still in development. In this study, by conducting homogenous time-resolved fluorescence resonance energy transfer (HTRF) assay, we identified a potential, novel BPTF inhibitor scaffold Sanguinarine chloride with the IC50 value of 344.2 ± 25.1 nM. Biochemical analysis revealed that compound Sanguinarine chloride exhibited high binding affinity to the BPTF bromodomain. Molecular docking predicted the binding mode of Sanguinarine chloride and elucidated the activities of its derivatives. Moreover, Sanguinarine chloride showed a potent anti-proliferative effect in MIAPaCa-2 cells and inhibited the expression of BPTF target gene c-Myc. Taken together, Sanguinarine chloride provides a qualified chemical tool for developing potent BPTF bromodomain inhibitors.

BPTF bromodomain

BPTF inhibitors

HTRF

c-Myc

bromodomain PHD finger transcription factor

nucleosome remodeling factor

homogenous time-resolved fluorescence resonance energy transfer

surface plasmon resonance assays

glutathione S-transferase

Carr-Purcell-Meiboom-Gill

nuclear magnetic resonance

All data generated or analysed during this study are included in this published article [and its supplementary information files]

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