selective CBP and EP300 degraders

Selective CBP and EP300 degraders are a series of heterobifunctional small molecules (PROTACs) developed by Foghorn Therapeutics to specifically target and eliminate either CREB-binding protein (CBP) or Histone acetyltransferase p300 (EP300). These paralogous histone acetyltransferases share high structural similarity, and previous dual inhibitors have been limited by hematopoietic toxicity. By utilizing the VHL E3 ligase to induce proteasomal degradation of only one paralog, these degraders exploit synthetic lethal relationships—such as the dependency of EP300-mutant gastric and colorectal cancers on CBP, or the lineage dependency of hematological cancers on EP300. This selective approach is designed to maximize anti-tumor activity while sparing healthy tissues, thereby widening the therapeutic window compared to non-selective inhibition.

Other names

selective CBP and EP300 degradersCBP-selective degradersEP300-selective degradersEP-300-selective degradersEP 300-selective degraders