MI-2 (Menin-MLL Inhibitor)

製品コードS7618 バッチS761802

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.

1271738-62-5

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

75 mg/mL (199.7 mM)

Ethanol

75 mg/mL (199.7 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

2%DMSO 1 30%PEG300 2 2%Tween80 3 66%ddH2O

3.0mg/ml

Taking the 1 mL working solution as an example, add 20 μL of 150 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 660 μL of ddH2O to adjust the volume to 1 mL. 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-2 (Menin-MLL Inhibitor) is a potent menin-MLL interaction inhibitor with IC50 of 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]

製品説明

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

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 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.

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：

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

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。