Home Epigenetics Histone Methyltransferase inhibitor - MLL inhibitor MI-503

MI-503

Catalog No.S7817

For research use only.

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.

MI-503 Chemical Structure

CAS No. 1857417-13-0

Selleck's MI-503 has been cited by 4 Publications

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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.
Targets
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].
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
mouse bone marrow cells M1zDWmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NIjqb5k4KGSjeYO= MlPzS5Jwf3SqIHnubIljcXSrb36gc4YhVUyOLVHGPUB1emGwc3\vdo1m\CCvb4Xz[UBjd26nIH3hdpJwfyClZXzsd{Bi\nSncjC3JIRigXNiYomgUXRVKGG|c3H5MEBIUTVyIE2gNE4zOiEQvF2u M3ryXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4N{S0O|Y4Lz5{Nke0OFc3PzxxYU6=
Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot MLL / Menin 27888797
Growth inhibition assay Cell viability 25817203
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].

Protocol (from reference)

Cell Research:[1]
  • 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.
Animal Research:[1]
  • Animal Models: Mouse models of MLL leukemia (BALB/c nude mice)
  • Dosages: 15 mg/kg
  • Administration: i.v.

Solubility (25°C)

In vitro

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

Chemical Information

Molecular Weight 564.63
Formula

C28H27F3N8S
CAS No. 1857417-13-0
Storage 3 years -20°C powder
2 years -80°C in solvent
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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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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