RB-231

RB-231 is a first-in-class small molecule inhibitor of the Polycomb repressive complex 1 (PRC1), specifically targeting the RING1A/B protein core. Developed at the University of Michigan, RB-231 binds directly to RING1A/B at the nucleosome interface, preventing PRC1 complex binding and the monoubiquitination of histone H2A lysine 119 (H2Aub). This inhibition leads to the de-repression of target genes, such as the p21 cell cycle inhibitor (CDKN1A), resulting in cell growth inhibition, apoptosis, and myeloid differentiation in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) models. Preclinical studies suggest selectivity for leukemic stem cells while sparing normal hematopoietic cells.