A-241

A-241 is a selective small-molecule catalytic inhibitor of the histone acetyltransferases (HATs) P300 (EP300) and CBP (CREBBP). Developed by AbbVie, A-241 targets the acetyltransferase domain of these proteins, which serve as critical transcriptional co-activators. By inhibiting the acetylation of histones and non-histone substrates, A-241 disrupts oncogenic transcriptional programs, particularly those dependent on MYC and IRF4, which are essential for the survival of multiple myeloma cells. Preclinical studies demonstrate that A-241 induces potent apoptotic and anti-proliferative effects and causes genome-wide histone deacetylation, especially at enhancer regions. It is frequently utilized in epigenetic research alongside the related inhibitor A-485 to explore vulnerabilities in hematologic malignancies.