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Mechanism of inhibition of menin-MLL by small molecules targeting MBM1 site on menin. A. MI-2-2 binds to menin and directly competes with MBM1 peptide. B. MI-2-2 does not compete with MBM2 peptide. C. Proposed two-step mechanism of inhibition of MLL containing both MBM1 and MBM2 via MI-2-2. Graphs represent fluorescence polarization experiments showing inhibition of binding of different MLL fragments to menin via MI-2-2 [25].
