Background:

MI-2 is a Menin-MLL inhibitor with IC50 value of 0.45 μM [1].

Mixed-lineage leukemia (MLL) is a common target of chromosomal translocations in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The leukemogenic activity of MLL fusion proteins is dependent on their direct interaction with menin, which is a tumor suppressor that directly controls cell growth in endocrine organs [1].

MI-2 is a Menin-MLL inhibitor. MI-2 bound to the wild-type menin but didn’t bind M278K and Y323K menin mutants. In HEK293 cells transfected with Flag-MLL-AF9, MI-2 effectively inhibited the menin-MLL-AF9 interaction without affecting the expression level of menin and MLL-AF9. In mouse bone marrow cells (BMC) transduced with MLL-AF9 and MLL-ENL, MI-2 blocked proliferation of BMC with GI50 value of about 5 μM. Also, MI-2 inhibited colony formation in BMC transduced with MLL-AF9. In a series of human MLL leukemia cell lines, MI-2 significantly inhibited translocation in a dose dependant way [1].

Reference:
[1].  Grembecka J, He S, Shi A, et al. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia. Nat Chem Biol, 2012, 8(3): 277-284.