M-525

M-525 is a first-in-class, highly potent, irreversible and covalent menin-MLL protein-protein interaction inhibitor. M-525 binds to menin with an IC₅₀ of 3 nM and achieves low nanomolar potencies in cell growth inhibition and in suppression of MLL regulated gene expression in MLL leukemia cells. Anti-leukemia activity^[1]. In Vitro: M-525 achieves an IC₅₀ of 3 nM in the MV4;11 cell line and has an IC₅₀ of 2 µM in the HL-60 cell line. M-525 (3-300 nM; 24 h) is potent and effective in suppressing the expression of MEIS1 and HOX genes in MV4;11 cells carrying the MLL-AF4 fusion and in MOLM-13 cells carrying the MLL-AF9 fusion. It demonstrates high cellular specificity over non-MLL leukemia cells^[1].