OR-S1

OR-S1 is a small molecule dual inhibitor of Enhancer of Zeste Homolog 1 (EZH1) and Enhancer of Zeste Homolog 2 (EZH2). It is a structural analog of the clinical-stage compound valemetostat (DS-3201). OR-S1 functions as an epigenetic modulator by inhibiting the methyltransferase activity of EZH1 and EZH2, which are the catalytic subunits of the Polycomb Repressive Complex 2 (PRC2). This inhibition leads to a reduction in the trimethylation of histone H3 lysine 27 (H3K27me3), resulting in the de-repression of tumor suppressor genes such as CDKN1C (p57, KIP2). Preclinical studies have demonstrated that OR-S1 can overcome ibrutinib resistance in mantle cell lymphoma (MCL) by inducing cell cycle arrest and inhibiting tumor growth.