IHK-44

IHK-44 is a potent small molecule dual inhibitor of the histone acetyltransferases CREB-binding protein (CBP) and p300. Developed at Case Western Reserve University, the compound was designed using structure-based drug design to address the epigenetic dependencies of fusion-positive rhabdomyosarcoma (FP-RMS). FP-RMS is driven by the PAX3-FOXO1 (P3F) fusion oncoprotein, which relies on CBP/p300 for its transcriptional activity. IHK-44 selectively suppresses P3F-driven transcription by targeting 3D clusters of histone acetylation that are enhancer-rich and lack CpG islands. Preclinical data suggests that FP-RMS is hypersensitive to IHK-44, while normal cells and fusion-negative RMS remain resistant, positioning IHK-44 as a potential therapeutic candidate for pediatric soft tissue carcinomas.