The chromatin regulators CBP and p300 maintain gene expression programs through lysine acetylation of chromatin and transcriptional regulators and by scaffolding functions mediated by several protein-protein interaction domains. We have developed a chemical degrader of p300/CBP, dCBP-1, using in silico modeling and cellular activity assays including capillary-based immunodetection assays (ProteinSimple, WES). We have found that dCBP-1 is exceptionally potent at killing multiple myeloma cells and can abolish the enhancer that drive MYC oncogene expression. As an efficient degrader of this unique class of chromatin regulators, dCBP-1 will be a useful tool for understanding p300/CBP activity at enhancers in both normal and diseased cells.