EPZ5676 is a potent and selective inhibitor of the histone methyltransferase DOT1L, an enzyme involved in epigenetic regulation. It is primarily used in research settings to study the role of DOT1L in gene expression and cellular differentiation, particularly in hematological cancers. Its most notable application is in the investigation of MLL-rearranged leukemias, where aberrant DOT1L activity contributes to oncogenic gene expression. By inhibiting DOT1L, EPZ5676 reduces the methylation of histone H3 at lysine 79 (H3K79), leading to the suppression of leukemia-promoting genes. This makes it a valuable tool compound for validating DOT1L as a therapeutic target and for guiding the development of epigenetic therapies for acute leukemias.