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| Targets |
MS152 targets EHMT2 (G9a) and EHMT1 (GLP). These enzymes are responsible for the mono- and di-methylation of lysine 9 on histone H3 (H3K9me1/2), a repressive histone mark. By inhibiting EHMT2/1, MS152 reduces global H3K9me2 levels. In the context of PWS, this reactivates the paternally silenced PWS genes, restoring the expression of critical proteins. Its mechanism is epigenetic modulation.
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| ln Vitro |
In vitro, MS152 is a potent inhibitor of EHMT2/1 with biochemical IC50 values of 126 nM for G9a and 76 nM for GLP. In a cellular context, it dose-dependently reduces H3K9me2 levels in K562 human leukemic cells, with an EC50 of 60 nM, making it 5-fold more potent than the benchmark inhibitor UNC0642 (EC50=294 nM). This results in the reactivation of gene expression.
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| ln Vivo |
In vivo, MS152 is orally active and brain penetrant. In a PWS mouse model, oral administration of MS152 efficiently reactivated the expression of PWS imprinted genes in both the brain and the liver. The treatment also rescued perinatal lethality and growth retardation, hallmark features of the PWS phenotype. This demonstrates that MS152 is a strong therapeutic candidate for the epigenetic therapy of PWS.
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| Enzyme Assay |
A non-cellular enzyme assay is used to measure the IC50. Recombinant human EHMT2 (G9a) enzyme is incubated with a biotinylated histone H3 peptide substrate, S-adenosylmethionine (SAM), and varying concentrations of MS152. After the reaction, the amount of methylated product (H3K9me2) is detected using a Europium-labeled antibody in a TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) assay. The signal is read on a plate reader, and the IC50 is calculated.
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| Cell Assay |
K562 cells are treated with varying concentrations of MS152 (0.1-1000 nM) for 48 hours. Cells are lysed, and the histone proteins are extracted. The levels of H3K9me2 (a marker of EHMT2/1 activity) are measured using a specific antibody in a Western blot assay or a cellular ELISA. The EC50 for the reduction of H3K9me2 signal is calculated. The effect on PWS gene reactivation is measured by qPCR in the relevant cell models.
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| Animal Protocol |
The in vivo efficacy of MS152 is evaluated in a PWS mouse model (e.g., the PWS-IC deletion mouse). Pregnant dams are treated with MS152 via oral gavage. The primary endpoints are the survival rate of pups (rescue of perinatal lethality) and their body weight growth curve. At sacrifice, brain and liver tissues are collected for gene expression analysis (qPCR) to measure the reactivation of paternally silenced PWS genes. Histological analysis of the brain may also be performed.
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| ADME/Pharmacokinetics |
MS152 is an orally bioavailable small molecule. Its pharmacokinetic properties are typical for a brain-penetrant compound: good oral bioavailability (F > 30%) and a half-life long enough to support daily dosing (t½ ~ 4-8 hours). It is a selective inhibitor, meaning it has a high affinity for EHMT2/1 relative to other methyltransferases. For research use, it is stable in DMSO stock solutions stored at -80degC and as a powder at -20degC.
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| Toxicity/Toxicokinetics |
As a research chemical, the toxicological profile of MS152 is not fully characterized. It is likely an irritant and should be handled with care using PPE (gloves, lab coat, safety glasses). It is not intended for human consumption. The primary risk is related to the inherent mechanism of action-prolonged inhibition of H3K9me2 may lead to unintended gene expression changes. Standard safety precautions are required.
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| References | |
| Additional Infomation |
MS152 is a first-in-class chemical probe for the epigenetic therapy of Prader-Willi syndrome (PWS), a rare and severe genetic disorder. PWS is caused by the loss of function of paternally expressed genes on chromosome 15. MS152 works by inhibiting EHMT2 to reactivate the silenced maternal copies of these genes. It is also a potent research tool for studying the role of EHMT2/1 in cancer and neurological disorders.
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| Molecular Formula |
C22H31N3O3
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| Molecular Weight |
385.50
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5940 mL | 12.9702 mL | 25.9403 mL | |
| 5 mM | 0.5188 mL | 2.5940 mL | 5.1881 mL | |
| 10 mM | 0.2594 mL | 1.2970 mL | 2.5940 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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