Definition

An orally bioavailable protein-protein interaction (PPI) inhibitor of the menin-mixed lineage leukemia (MLL; mixed-lineage leukemia 1; MLL1; myeloid/lymphoid leukemia; histone-lysine N-methyltransferase 2A; KMT2A) proteins, with potential antineoplastic activity. Upon oral administration, menin-MLL interaction inhibitor JNJ-75276617 inhibits the interaction between the two proteins menin and MLL and the formation of the menin-MLL complex. This reduces the expression of downstream target genes and results in an inhibition of the proliferation of leukemic cells with either KMT2A alterations such as gene rearrangements (KMT2A-r), duplications, and amplification, or nucleophosmin 1 gene (NPM1) alterations. The menin-MLL complex plays a key role in the survival, growth, transformation and proliferation of certain kinds of leukemia cells.