MI-3 (Menin-MLL Inhibitor)

製品コードS7619 バッチS761901

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₈H₂₅N₅S₂

分子量

375.55

CAS No.

1271738-59-0

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

19 mg/mL (50.59 mM)

Ethanol (warmed with 50ºC water bath)

19 mg/mL (50.59 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	MI-3 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 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]

製品説明

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

プロトコル(参考用のみ)

キナーゼアッセイ	High Throughput Screening
キナーゼアッセイ	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.
細胞アッセイ	細胞株	MLL-AF9 and E2A-HLF transduced murine BMC
	濃度	~20 μM
	反応時間	12 days
	実験の流れ	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.

参考

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

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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