UNC1999

UNC1999 is a potent, selective, and orally bioavailable small-molecule inhibitor of the histone methyltransferases EZH2 and EZH1. Developed as a chemical probe by researchers at the University of North Carolina at Chapel Hill, it acts as a cofactor-competitive inhibitor by competing with S-adenosyl-L-methionine (SAM). UNC1999 effectively reduces global levels of histone H3 lysine 27 trimethylation (H3K27me3), an epigenetic mark associated with gene silencing. It has been widely utilized in preclinical research to investigate the role of EZH2 in various malignancies, including small cell lung cancer (SCLC), mixed-lineage leukemia (MLL)-rearranged leukemias, and lymphomas. In research settings, it has demonstrated the ability to inhibit the growth of EZH2-dependent cancer cells and has been explored as a potential radiosensitizer.