MI-463

Research use only, not for human use.

MI-463 is a highly potent and orally bioavailable small-molecule inhibitor of menin–MLL.

MI-463 is a highly potent and orally bioavailable small-molecule inhibitor of menin–MLL (IC50=15.3 nM; Kd=9.9 nM); shows profound effects in MLL leukemia cells and substantial survival benefit in mouse models of MLL leukemia.

MI-463 can reach the target protein in mammalian cells and effectively inhibit the menin-mLL-AF9 interaction at sub-micromolar concentrations. Treatment of murine bone marrow cells (BMC) transformed with the mLL-AF9 oncogene with MI-463 results in substantial growth inhibition, with GI50 of 0.23 μM.

MI-463 achieves high level in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability (45%). Pharmacologic inhibition of the menin-mLL interaction substantially delays progression of mLL leukemia in murine models through on-target activity without causing toxicity. MI-463 induces strong inhibition of tumor growth with once daily intraperitoneal (i.p.) administration. The expression of mLL fusion protein target genes, HOXA9 and MEIS1, are significant reduced upon treatment with MI-463. 20 days treatment of MV4;11 xenograft recipient mice with MI-463 also results in a substantial delay in leukemia progression as manifested by a marked decrease in the bioluminescence level which is associated with a significant decrease in the population of leukemic cells in the peripheral blood, spleen and bone marrow samples.

MI463 | MI 463

Chromatin/Epigenetic

HMTase

HMTase

Cancer

——

1628317-18-9

484.5398

C24H23F3N6S

>98% (HPLC)

10 mM in DMSO

CC1=C2C(NC(C#N)=C2)=CC=C1CN(CC3)CCC3NC4=C(C=C(CC(F)(F)F)S5)C5=NC=N4

1H-Indole-2-carbonitrile, 4-methyl-5-[[4-[[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]-1-piperidinyl]methyl]-

(-20℃)

With Ice Pack

≥ 2 years