The SGC in collaboration with Pfizer has discovered a potent chemical probe for the YEATS family, PFI-8. The YEATS-domain containing proteins are responsible for epigenetic signaling via acylated lysines including acetylation and higher order acylations such as propionylation, butyrylation, and crotonylation. PFI-8 binds YEATS 1-4 with FRET Kis of 495, 330, 462, and 33 nM respectively using a biotin-tagged crotonylated H3 peptide. PFI-8N, a negative control compound showed FRET Ki of >20 mM.
Binding of YEATS4 to PFI-8
Cellular activity of PFI-8 using NanoBRET assay in HEK293 cells
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