MI-463 (C09-0968-024)

InformationMI-463 MI-463 is a potent inhibitor of Menin-MLL interaction with an IC50 value of 15.3 nM.TargetsMenin-MLL interaction (Cell-free assay) 15.3 nMIn vitroMI-463 demonstrates profound on-target activity in MLL leukemia cells. MI-463 results in substantial growth inhibition, with half-maximal growth inhibitory concentration (GI50) values of 0.23 μM, measured after 7 days of treatment in MLL leukemia cells. 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 vivoMI-463 shows substantial survival benefit in mouse models of MLL leukemia. It has very favorable druglike properties, including metabolic stability and PK profile in mice. MI-463 achieves high levels in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability(∼45%). 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.Cell Research(from reference)Cell lines：leukemia cells Incubation Time：6 or 7 days. Specifications and Purity: 10mM in DMSO. Molecular Formula: C24H23F3N6S. Molecular Weight: 484.54. PubChem CID: 90455046. Isomeric SMILES: CC1=C(C=CC2=C1C=C(N2)C#N)CN3CCC(CC3)NC4=C5C=C(SC5=NC=N4)CC(F)(F)F.