GNE-781

GNE-781 is a potent, selective, and orally bioavailable small molecule inhibitor of the bromodomains of the paralogous histone acetyltransferases CBP (CREB-binding protein) and p300 (EP300). Developed by Genentech, GNE-781 functions as an epigenetic modulator by disrupting the interaction between the CBP/p300 bromodomains and acetylated lysine residues on histones. This disruption leads to the downregulation of oncogenic transcription factors and genes associated with super-enhancers, such as MYC and EVI1. Preclinical research has highlighted its potential in treating various malignancies, including acute myeloid leukemia (AML) and androgen receptor-positive prostate cancer, often showing synergistic effects when combined with other inhibitors of the p300/CBP complex, such as acetyltransferase domain inhibitors.