navlimetostat

Navlimetostat (BMS-986158) is an orally bioavailable, potent, and selective dual inhibitor of Enhancer of Zeste Homolog 1 (EZH1) and Enhancer of Zeste Homolog 2 (EZH2), developed by Bristol Myers Squibb. EZH1 and EZH2 are the catalytic subunits of the Polycomb Repressive Complex 2 (PRC2), which methylates histone H3 at lysine 27 (H3K27me3), a modification that leads to the transcriptional silencing of genes involved in cell differentiation and tumor suppression. In many cancers, EZH2 is overexpressed or mutated, contributing to oncogenesis. By inhibiting both EZH1 and EZH2, navlimetostat reduces H3K27me3 levels and restores the expression of tumor suppressor genes, thereby inhibiting tumor growth. It is currently being investigated in clinical trials for the treatment of advanced solid tumors and hematologic malignancies, including myelofibrosis and lymphomas.