title: Specific Direct Small Molecule p300/β-Catenin Antagonists Maintain Stem Cell Potency.
abstract: 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.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Cu
authors.initials: C
authors.lastname: Nguyen
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Yasuda
authors.forename: Michael
authors.initials: M
authors.lastname: McMillan
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: USC Norris Comprehensive Cancer Center, 1450 Biggy Street, NRT4501, Los Angeles, CA 90033, USA. kahnm@usc.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Kahn
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D050881:E1A-Associated p300 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057809:HEK293 Cells; D000066449:Human Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D054852:Small Molecule Libraries; D051176:beta Catenin; D050882:CREB-Binding Protein; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human