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MI-463 is a highly potent and orally bioavailable small molecule inhibitor of the Menin-MLL interaction, with an IC50 value of 15.3 nM. MI-463 is effective in inducing differentiation of MLL leukemia cells. Treatment with sub-micromolar concentrations of MI-463 also leads to markedly reduced expression of Hoxa9 and Meis1, downstream targets of MLL fusion proteins substantially upregulated in MLL leukemias.
In vivo, MI-463 induces strong inhibition of tumor growth with once daily intraperitoneal (i.p.) administration. In a mouse xenograft model using MV4;11 human MLL leukemia cells implanted into BALB/c nude mice, MI-463 induces strong inhibition of tumor growth with once-daily intraperitoneal (i.p.) administration. It does not impair normal hematopoiesis in vivo.
| Molecular Weight | 484.54 |
| Formula | C24H23F3N6S |
| CAS Number | 1628317-18-9 |
| Solubility (25°C) | DMSO: ≥ 85 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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