For research use only.

Catalog No.S7817

1 publication

MI-503 Chemical Structure

CAS No. 1857417-13-0

MI-503 is a potent and selective Menin-MLL inhibitor with IC50 of 14.7 nM. It shows pronounced growth suppressive activity in a panel of human MLL leukemia cell lines(GI50 at 250 nM-570 nM range), but only a minimal effect in human leukemia cell lines without MLL translocations.

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Selleck's MI-503 has been cited by 1 publication

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Biological Activity

Description MI-503 is a potent and selective Menin-MLL inhibitor with IC50 of 14.7 nM. It shows pronounced growth suppressive activity in a panel of human MLL leukemia cell lines(GI50 at 250 nM-570 nM range), but only a minimal effect in human leukemia cell lines without MLL translocations.
Menin-MLL interaction [1]
(Cell-free assay)
14.7 nM
In vitro

Treatment of murine bone marrow cells (BMC) transformed with the MLL-AF9 oncogene with MI-503 results in substantial growth inhibition, with half-maximal growth inhibitory concentration (GI50) values of 0.22 μM, measured after 7 days of treatment. The cell growth inhibitory effect of MI-503 is time-dependent, with a pronounced effect achieved after 7-10 days of treatment. MI-503 is also very effective in inducing differentiation of MLL leukemia cells and substantially increases expression of CD11b, a myeloid differentiation marker. These effects are accompanied by reduced c-kit (CD117) expression, a marker associated with leukemia stem cells (LSCs). Treatment with sub-micromolar concentrations of MI-503 also leads to markedly reduced expression of Hoxa9 and Meis1, downstream targets of MLL fusion proteins substantially upregulated in MLL leukemias[1].

Methods Test Index PMID
Western blot
MLL / Menin ; 

PubMed: 27888797     

Western blot depicting MLL1 and menin protein expression after 6 day treatment with MI-503 or MI-NC in Ewing sarcoma cells.

Growth inhibition assay
Cell viability; 

PubMed: 25817203     

Titration curves from MTT assay performed for 7 days of treatment of human MLL leukemia cell lines with MI-503: MV4;11 (MLL-AF4), MOLM-13 (MLL-AF9), KOPN-8 (MLL-ENL) and SEM (MLL-AF4) and control AML cell lines without MLL translocations: HL-60, NB4 and Jurkat; mean ± SD, n = 4. 

In vivo MI-503 has very favorable drug-like properties, including metabolic stability and pharmacokinetic profile in mice. It blocks hematologic tumors in vivo and reduces MLL leukemia tumor burden. MI-503 achieves high level in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability (~75%). Prolonged treatment (38 days) with MI-503 induces no toxicity in mice as reflected by no alterations in the body weight and no morphological changes in liver and kidney tissues. MI-503 could substantially improve survival of MLL leukemic mice and does not impair normal hematopoiesis in vivo[1].


Cell Research:[1]
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  • Cell lines: MV4;11 human leukemia cells expressing MLL-AF4
  • Concentrations: --
  • Incubation Time: 7days
  • 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. Media is changed at day 4, viable cell numbers are restored to the original concentration and compounds are re-supplied. MTT cell proliferation assay kit is then employed, 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 Real-time quantitative PCR (qRT-PCR) after 6 days of incubation of compounds with cells, with media 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.
    (Only for Reference)
Animal Research:[1]
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  • Animal Models: Mouse models of MLL leukemia (BALB/c nude mice)
  • Dosages: 15 mg/kg
  • Administration: i.v.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL warmed (177.1 mM)
Ethanol 15 mg/mL warmed (26.56 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 564.63


CAS No. 1857417-13-0
Storage powder
in solvent
Synonyms N/A
Smiles CC1=C(C=CC2=C1C=C(N2CC3=CNN=C3)C#N)CN4CCC(CC4)NC5=C6C=C(SC6=NC=N5)CC(F)(F)F

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Histone Methyltransferase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID