EP300 and cancer: Despite strong evidence linking CREBBP/EP300 to pathological transcriptional programs in cancer, prior to the late 2010s, inhibitors targeting CREBBP/EP300 acetyltransferase activity were limited to cell impermeable substrate analogs (e.g. Lys-CoA), nonselective natural products (e.g. curcumin), or reactive synthetic compounds (e.g. C646) [6].