MI-2 (Menin-MLL Inhibitor)

Catalog No.S7618 Batch:S761801

Technical Data

Formula	C₁₈H₂₅N₅S₂
Molecular Weight	375.55	CAS No.	1271738-62-5
Solubility (25°C)*	In vitro	DMSO	75 mg/mL (199.7 mM)
		Ethanol	75 mg/mL (199.7 mM)
		Water	Insoluble
* <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.)

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Biological Activity

Description

MI-2 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 446 nM.

Targets

Menin-MLL interaction ^[1]
(Cell-free assay)

446 nM

In vitro

In HEK293 cells, MI-2 accessed the protein target and effectively inhibits the menin-MLL-AF9 interaction. MI-2 effectively blocks MLL fusion protein-mediated leukemic transformation by downregulating the expression of target genes required for MLL fusion protein oncogenic activity. MI-2 also effectively blocks cell proliferation, and induces cell apoptosis in human MLL leukemia cell lines harboring different MLL translocations. ^[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 methycellulose 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 methycellulose 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-2 (Menin-MLL Inhibitor) has been cited by 10 publications

Studies of Epigenetics and Properties of B Cell Receptor in WALDENSTRÖM Macroglobulinemia (WM) [ ProQuest, 2023, 30484965]	PubMed: none
Glioblastoma stem cell-specific histamine secretion drives pro-angiogenic tumor microenvironment remodeling [ Cell Stem Cell, 2022, S1934-5909(22)00417-9]	PubMed: 36265493
Epigenetic modifier balances Mapk and Wnt signalling in differentiation of goblet and Paneth cells [ Life Sci Alliance, 2022, 5(4)e202101187]	PubMed: 35064075
Hyperglycemic Memory of Innate Immune Cells Promotes In Vitro Proinflammatory Responses of Human Monocytes and Murine Macrophages [ J Immunol, 2021, ji1901348]	PubMed: 33431659
The Wnt-Driven Mll1 Epigenome Regulates Salivary Gland and Head and Neck Cancer [ Cell Rep, 2019, 26(2):415-428]	PubMed: 30625324
Menin Associates with the Mitotic Spindle and is Important for Cell Division [ Endocrinology, 2019, 10.1210/en.2019-00274]	PubMed: 31211356
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
Glutaminolysis Mediated by MALT1 Protease Activity Facilitates PD-L1 Expression on ABC-DLBCL Cells and Contributes to Their Immune Evasion. [ Front Oncol, 2018, 8:632]	PubMed: 30619766
A RUNX2-Mediated Epigenetic Regulation of the Survival of p53 Defective Cancer Cells [ PLoS Genet, 2016, 12(2):e1005884]	PubMed: 26925584
Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation. [Grandy RA, et al. Mol Cell Biol, 2015, 36(4):615-27]	PubMed: 26644406

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