MI-503

Catalog No.S7817 Batch:S781701

Technical Data

Formula

C₂₈H₂₇F₃N₈S

Molecular Weight

564.63

CAS No.

1857417-13-0

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (177.1 mM)

Ethanol

15 mg/mL (26.56 mM)

Water

Insoluble

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

Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	0.5mg/ml	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	0.125mg/ml	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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

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.

Targets

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

14.7 nM

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 MI-503 is time-dependent, with a pronounced effect achieved after 7-10 days of treatment. MI-503 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 MI-503 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. MI-503 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 MI-503 induces no toxicity in mice as reflected by no alterations in the body weight and no morphological changes in liver and kidney tissues. MI-503 could substantially improve survival of MLL leukemic mice and does not impair normal hematopoiesis in vivo^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines MV4;11 human leukemia cells expressing MLL-AF4 Concentrations -- Incubation Time 7days Method 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 menin-MLL inhibitors 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 menin-MLL inhibitors for 7 days, then harvested, washed and incubated with Pacific Blue rat anti-mouse CD11b antibody before being analyzed by flow cytometry.
Animal Study:^{^[1]}	Animal Models Mouse models of MLL leukemia (BALB/c nude mice) Dosages 15 mg/kg Administration i.v.

Cell Assay:^{^[1]}

Cell lines
MV4;11 human leukemia cells expressing MLL-AF4
Concentrations
--
Incubation Time
7days
Method
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 menin-MLL inhibitors 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 menin-MLL inhibitors for 7 days, then harvested, washed and incubated with Pacific Blue rat anti-mouse CD11b antibody before being analyzed by flow cytometry.

Animal Study:^{^[1]}

Animal Models
Mouse models of MLL leukemia (BALB/c nude mice)
Dosages
15 mg/kg
Administration
i.v.

References

[1] Borkin D, et al. Cancer Cell. 2015, 27(4):589-602.

Selleck's MI-503 has been cited by 9 publications

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
Combined targeting of the Menin-MLL chromatin regulatory complex and the FLT3 tyrosine kinase as a novel therapeutic approach against NPM1mut and MLL-r [ Johannes Gutenberg-Universität Mainz, 2021, 10.25358/openscience-5949]	PubMed: None
Menin and Menin-Associated Proteins Coregulate Cancer Energy Metabolism [ Cancers (Basel), 2020, 12(9)E2715]	PubMed: 32971831
Menin-MLL inhibitor blocks progression of middle ear cholesteatoma in vivo [ Int J Pediatr Otorhinolaryngol, 2020, 140:110545]	PubMed: 33302022

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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