XP-524

**XP-524** is a potent dual inhibitor of bromodomain and extraterminal motif (BET) protein BRD4 and histone acetyltransferase EP300/CBP, designed to overcome limitations of single-agent BET inhibitors in pancreatic ductal adenocarcinoma (PDAC). Developed by researchers led by Ajay Rana at the University of Illinois Chicago (UIC), it demonstrates superior potency to benchmark BET inhibitor JQ1 (IC50 5.8 nM for BRD4-BD1, 1.5 nM for BRD4-BD2) and comparable efficacy to JQ1 combined with EP300/CBP inhibitor SGC-CBP30, repressing oncogenic KRAS transcription and downstream MAPK signaling, preventing neoplastic transformation, and extending survival in transgenic PDAC mouse models. XP-524 reprograms the tumor microenvironment by enhancing self-peptide presentation, cytotoxic T lymphocyte recruitment, and sensitivity to anti-PD-1 checkpoint inhibition, doubling median survival when combined.[1][2][3]