Home Epigenetics Histone Methyltransferase inhibitor - MLL inhibitor MI-463 For research use only.

MI-463

MI-463 is a potent inhibitor of Menin-MLL interaction with an IC50 value of 15.3 nM.

MI-463 Chemical Structure

MI-463 Chemical Structure

CAS No. 1628317-18-9

Purity & Quality Control

Batch: S781601 DMSO]96 mg/mL]false]Ethanol]22 mg/mL]false]Water]Insoluble]false Purity: 99.83%
99.83

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Biological Activity

Description MI-463 is a potent inhibitor of Menin-MLL interaction with an IC50 value of 15.3 nM.
Targets
Menin-MLL interaction [1]
(Cell-free assay)
15.3 nM
In vitro
In vitro MI-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[1].
Cell Research Cell lines leukemia cells
Concentrations --
Incubation Time 6 or 7 days
Method For viability assays, leukemia cells are plated at relevant concentrations and treated with compounds or 0.25% DMSO and cultured at 37°C for 7 days. Medium is changed at day 4, viable cell numbers are restored to the original concentration, and compounds are re-supplied. The MTT cell proliferation assay kit (Roche) is then used, and plates are read for absorbance at 570 nm using a PHERAstar BMG microplate reader. Effect of menin-MLL inhibitors on expression level is assessed by qRT-PCR after 6 days of incubation of compounds with cells, with medium changed and compound re-supply at day 3. For cell differentiation studies, leukemia cells are treated with menin-MLL inhibitors for 7 days, then harvested, washed, and incubated with Pacific Blue rat anti-mouse CD11b antibody before being analyzed by flow cytometry.
In Vivo
In vivo MI-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[1].
Animal Research Animal Models C57BL/6 mice
Dosages 15 mg/kg
Administration I.V.

Chemical Information & Solubility

Molecular Weight 484.54 Formula

C24H23F3N6S
CAS No. 1628317-18-9 SDF Download MI-463 SDF
Smiles CC1=C(C=CC2=C1C=C(N2)C#N)CN3CCC(CC3)NC4=C5C=C(SC5=NC=N4)CC(F)(F)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 96 mg/mL ( (198.12 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 22 mg/mL

Water : Insoluble


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In vivo
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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