MI-503

製品コードS7817 バッチS781701

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

C₂₈H₂₇F₃N₈S

分子量

564.63

CAS No.

1857417-13-0

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

100 mg/mL (177.1 mM)

Ethanol (warmed with 50ºC water bath)

15 mg/mL (26.56 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.500mg/ml (0.89mM)	Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.125mg/ml (0.22mM)	Taking the 1 mL working solution as an example, add 50 μL of 2.5 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-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.
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 this compound is time-dependent, with a pronounced effect achieved after 7-10 days of treatment. It 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 this chemical also leads to markedly reduced expression of Hoxa9 and Meis1, downstream targets of MLL fusion proteins substantially upregulated in MLL leukemias^[1].
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. This compound 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 this chemical induces no toxicity in mice as reflected by no alterations in the body weight and no morphological changes in liver and kidney tissues. It could substantially improve survival of MLL leukemic mice and does not impair normal hematopoiesis in vivo^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	MV4;11 human leukemia cells expressing MLL-AF4
	濃度	--
	反応時間	7days
	実験の流れ	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 this compound 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 this chemical for 7 days, then harvested, washed and incubated with Pacific Blue rat anti-mouse CD11b antibody before being analyzed by flow cytometry.
動物実験	動物モデル	Mouse models of MLL leukemia (BALB/c nude mice)
	投薬量	15 mg/kg
	投与方法	i.v.

参考

https://pubmed.ncbi.nlm.nih.gov/25817203/

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：

Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters [ Nat Genet, 2025, 57(1):165-179]	PubMed: 39806204
Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters [ Nat Genet, 2025, 57(1):165-179]	PubMed: 39806204
Menin inhibitor MI-503 exhibits potent anti-cancer activity in osteosarcoma [ Sci Rep, 2025, 15(1):7059]	PubMed: 40016386
Nuclear Phase Separation Drives NPM1-mutant Acute Myeloid Leukemia [ bioRxiv, 2025, 2025.05.23.655671]	PubMed: 40501735
MLL1 regulates cytokine-driven cell migration and metastasis [ Sci Adv, 2024, 10(11):eadk0785]	PubMed: 38478601
Targeting Menin disrupts the KMT2A/B and polycomb balance to paradoxically activate bivalent genes [ Nat Cell Biol, 2023, 25(2):258-272]	PubMed: 36635503
Therapeutic targeting of metabolic vulnerabilities in cancers with MLL3/4-COMPASS epigenetic regulator mutations [ J Clin Invest, 2023, 133(13)e169993]	PubMed: 37252797
Combinatorial targeting of a chromatin complex comprising Dot1L, menin and the tyrosine kinase BAZ1B reveals a new therapeutic vulnerability of endocrine therapy-resistant breast cancer [ Breast Cancer Res, 2022, 24(1):52]	PubMed: 35850772
Combinatorial targeting of menin and the histone methyltransferase DOT1L as a novel therapeutic strategy for treatment of chemotherapy-resistant ovarian cancer [ Cancer Cell Int, 2022, 22(1):336]	PubMed: 36333801
Super-enhancer Acquisition Drives FOXC2 Expression in Middle Ear Cholesteatoma [ J Assoc Res Otolaryngol, 2021, 10.1007/s10162-021-00801-7]	PubMed: 33861394

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。