MI-nc is a weak inhibitor of the menin-MLL fusion protein interaction with an IC50 of 193 μM. It can be used as a negative control compound for tests involving MI-2, which showed more binding potency with menin, blocked the menin-MLL interaction with an IC50 of 0.45 μM, and induced apoptosis in cells expressing MLL fusion proteins [1].
Menin, a product of the multiple endocrine neoplasia gene, is an essential co-factor of oncogenic MLL fusion proteins. MLL interacts with menin in a bivalent mode involving 2 N-terminal fragments of MLL, and the menin–MLL interaction is critical for development of acute leukemia. Inhibition of the menin interaction with MLL fusion proteins is a very promising strategy to reverse their oncogenic activity [2].
References:
[1]. Grembecka J, He S, Shi A, et al. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia[J]. Nature chemical biology, 2012, 8(3): 277-284.
[2]. Yokoyama A, Somervaille T C P, Smith K S, et al. The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis[J]. Cell, 2005, 123(2): 207-218.