Despite their high degree of identity and even higher homology, the two Kat3 transcriptional
coactivators, CBP and p300, have distinct functions, particularly within the Wnt/β-catenin signaling cascade.
ICG-001, by directly binding to CBP but not p300, inhibits CBP/β-catenin transcription and has
served as an invaluable chemical genomic tool to dissect the Wnt signaling cascade and the divergent
roles of these two coactivators. However, to date no direct antagonist of the p300/β-catenin interaction
has been reported. We now report the identification and validation of the first highly specific, direct
p300/β-catenin antagonists, YH249/250 and their ability to maintain pluripotency in ESC.