MI-3 (Menin-MLL Inhibitor)

Catalog No.S7619 Batch:S761901

Technical Data

Formula

C₁₈H₂₅N₅S₂

Molecular Weight

375.55

CAS No.

1271738-59-0

Solubility (25°C)*

In vitro

DMSO

19 mg/mL (50.59 mM)

Ethanol

19 mg/mL (50.59 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 Corn oil

1.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

MI-3 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 648 nM.

Targets

Menin-MLL interaction ^[1]

648 nM

In vitro

In HEK293 cells, MI-3 accesses the protein target and effectively inhibits the menin-MLL-AF9 interaction. MI-3 effectively blocks MLL fusion protein-mediated leukemic transformation by downregulating the expression of target genes required for MLL fusion protein oncogenic activity. In human MLL leukemia cell lines harboring different MLL translocations, MI-3 effectively blocks cell proliferation, and induces apoptosis. ^[1]

Protocol (from reference)

Kinase Assay:^{^[1]}	High Throughput Screening FITC-MBM1 at 15 nM and menin at 150 nM in the FP buffer are mixed and incubated for 1h in the dark at room temperature. For point screening, the 0.2 μL of each compound (20 μM final concentration, 1% DMSO) is added to 20 μL of the aliquot of the protein-peptide mixture and incubated on 384-well plates in the dark at room temperature for 1h. In confirmation screening, the serial dilution plates with compounds in DMSO are prepared and used to titrate the menin-FITC-MBM1 complex. Change in fluorescence polarization is monitored at 525 nm after excitations at 495 nm using the PHERAstar microplate reader (BMG) and applied to determine IC50 values with the Origin 7.0 program.
Cell Assay:^{^[1]}	Cell lines MLL-AF9 and E2A-HLF transduced murine BMC Concentrations ~20 μM Incubation Time 12 days Method The MLL-AF9 and E2A-HLF transduced murine BMC are plated in 12-well plates at the concentration of 5×10³ cells/mL with 1 mL methylcellulose medium M3234 containing 20% IMDM medium, 1% penicillin/streptomycin, IL-3 and 0.25% DMSO or compounds. 6 days later colonies are stained with 100 μL iodonitrotetrazolium chloride at final concentration of 1 mg/mL, incubated at 37°C for 30 min and counted. To replate for the 2nd round, colonies are counted at day 6 without staining and cells were washed out by 1×PBS buffer and resuspended in IMDM medium containing 15% FBS, 1% penicillin/streptomycin and IL-3. 5×10³ cells are plated in 12-well plates with 1ml methylcellulose medium M3234 containing 20% IMDM medium, 1% penicillin/streptomycin, IL-3 and 0.25% DMSO or compounds. 6 days later colonies are stained and counted.

Kinase Assay:^{^[1]}

High Throughput Screening
FITC-MBM1 at 15 nM and menin at 150 nM in the FP buffer are mixed and incubated for 1h in the dark at room temperature. For point screening, the 0.2 μL of each compound (20 μM final concentration, 1% DMSO) is added to 20 μL of the aliquot of the protein-peptide mixture and incubated on 384-well plates in the dark at room temperature for 1h. In confirmation screening, the serial dilution plates with compounds in DMSO are prepared and used to titrate the menin-FITC-MBM1 complex. Change in fluorescence polarization is monitored at 525 nm after excitations at 495 nm using the PHERAstar microplate reader (BMG) and applied to determine IC50 values with the Origin 7.0 program.

Cell Assay:^{^[1]}

Cell lines
MLL-AF9 and E2A-HLF transduced murine BMC
Concentrations
~20 μM
Incubation Time
12 days
Method
The MLL-AF9 and E2A-HLF transduced murine BMC are plated in 12-well plates at the concentration of 5×10³ cells/mL with 1 mL methylcellulose medium M3234 containing 20% IMDM medium, 1% penicillin/streptomycin, IL-3 and 0.25% DMSO or compounds. 6 days later colonies are stained with 100 μL iodonitrotetrazolium chloride at final concentration of 1 mg/mL, incubated at 37°C for 30 min and counted. To replate for the 2nd round, colonies are counted at day 6 without staining and cells were washed out by 1×PBS buffer and resuspended in IMDM medium containing 15% FBS, 1% penicillin/streptomycin and IL-3. 5×10³ cells are plated in 12-well plates with 1ml methylcellulose medium M3234 containing 20% IMDM medium, 1% penicillin/streptomycin, IL-3 and 0.25% DMSO or compounds. 6 days later colonies are stained and counted.

References

[1] Grembecka J, et al. Nat Chem Biol. 2012, 8(3), 277-284.

Selleck's MI-3 (Menin-MLL Inhibitor) has been cited by 5 publications

macroH2A2 antagonizes epigenetic programs of stemness in glioblastoma [ Nat Commun, 2023, 14(1):3062]	PubMed: 37244935
ecDNA hubs drive cooperative intermolecular oncogene expression [ Nature, 2021, 10.1038/s41586-021-04116-8]	PubMed: 34819668
Co-inhibition of HDAC and MLL-menin interaction targets MLL-rearranged acute myeloid leukemia cells via disruption of DNA damage checkpoint and DNA repair. [ Clin Epigenetics, 2019, 11(1):137]	PubMed: 31590682
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740]	PubMed: 30135193
A RUNX2-Mediated Epigenetic Regulation of the Survival of p53 Defective Cancer Cells [ PLoS Genet, 2016, 12(2):e1005884]	PubMed: 26925584

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