"目录号: HY-15222
Epigenetics-
MI-2 抑制Menin-MLL相互作用，IC50为 446±28 nM。
Histone Methyltransferase
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生物活性
Description
MI-2 is aMenin-MLLinteraction inhibitor withIC50of 446±28 nM.
IC50& Target
IC50: 446±28 nM (Menin-MLL)[1]
In Vitro
The menin-MLL inhibitor MI-2 very effectively blocks proliferation of MLL-AF9 and MLL-ENL transduced BMC, with GI50values of about 5 μM. Assessment of diverse hydrophobic groups at R1 led to the development of several compounds with IC50values in the nanomolar range, including MI-2 (IC50= 446±28 nM) and MI-3 (IC50=648±25 nM).The dissociation constants measured for the menin-MLL inhibitors are at the nanomolar level, Kd=158 nM for MI-2. MI-2 can access the protein target and very effectively inhibit the menin-MLL-AF9 interaction in human cells. Furthermore, MI-2 shows only a small effect on the cell growth of E2A-HLF transduced BMC (GI50>50 μM), which may be due to inhibition of the menin interaction with wild-type MLL. Treatment with MI-2 results in GI50values below 10 μM in MV4;11 (harboring MLL-AF4; GI50=9.5 μM), KOPN-8 (MLL-ENL; GI50=7.2 μM) and ML-2 (MLL-AF6; GI50=8.7 μM), and in MonoMac6 (MLL-AF9; GI50=18 μM)[1].
References
[1].Grembecka J, et al. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia. Nature Chemical Biology (2012), 8(3), 277-284.