| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
PRMT6
MS117 specifically targets Protein Arginine Methyltransferase 6 (PRMT6). It is a potent, irreversible covalent inhibitor that binds to the active site of the enzyme with an IC50 of 18 nM. It exhibits moderate selectivity, being 6-fold more selective for PRMT6 over PRMT1 (IC50 = 0.1 uM) and PRMT8 (IC50 = 0.11 uM). Its covalent nature ensures prolonged target engagement and sustained inhibition of PRMT6 methyltransferase activity. |
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| ln Vitro |
In a time-dependent way, MS117 (Compound 4) suppresses the activity of PRMT6 methyltransferase[1]. When compared to PRMT1 (IC50 = 0.1 ± 0.025 µM) and PRMT8 (IC50 = 0.11 ± 0.01 µM), MS117 (Compound 4) exhibits moderate selectivity (6-fold) for PRMT6 [1].
In vitro, MS117 (Compound 4) inhibits PRMT6 methyltransferase activity in a time-dependent manner, as expected for an irreversible covalent inhibitor. It demonstrates an IC50 of 18 nM in a biochemical assay and shows moderate selectivity over other PRMT family members. This inhibition leads to changes in the methylation status of PRMT6 substrates, ultimately affecting gene expression and having a potential impact on cancer cell viability. |
| ln Vivo |
In vivo efficacy data for MS117 is not explicitly detailed in the provided summaries. As a first-in-class covalent inhibitor, it is expected to be used in xenograft mouse models to evaluate its anti-tumor activity in PRMT6-dependent cancers. The ability to be formulated for in vivo use (as indicated by solubility data) suggests it has the potential to be an active tool for in vivo pharmacology.
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| Enzyme Assay |
For a cell-free system, purified recombinant PRMT6 enzyme and a radiolabeled methyl donor, 3H-S-adenosyl-L-methionine (3H-SAM), are incubated with a suitable protein or peptide substrate (e.g., histone H4 peptide). The reaction is terminated, and the incorporation of radioactive methyl groups into the substrate is measured by scintillation counting. The compound is pre-incubated with the enzyme to assess its inhibitory activity and to confirm the time-dependent nature of the inhibition.
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| Cell Assay |
In cellular assays, cancer cell lines (e.g., triple-negative breast cancer cells) are treated with various concentrations of MS117. Cell viability is measured after 48-72 hours using an MTT or CellTiter-Glo assay to determine an IC50. Target engagement and efficacy are assessed by Western blotting of cell lysates using a specific antibody that detects the methylation mark generated by PRMT6 (e.g., H3R2me2a). A decrease in the specific methylation mark indicates successful on-target activity in cells.
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| Animal Protocol |
While a specific animal study protocol is not provided, the compound's solubility data (≥ 2.5 mg/mL in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline) indicates its suitability for intravenous (IV) or intraperitoneal (IP) injection. A typical protocol would involve administering MS117 by IP injection daily or every other day to mice bearing subcutaneous tumor xenografts. Tumor volume is measured with calipers to assess growth inhibition.
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| ADME/Pharmacokinetics |
Detailed ADME (Absorption, Distribution, Metabolism, and Excretion) data for MS117 is not provided. The compound is soluble in DMSO (100 mg/mL), and formulations for in vivo injection have been developed, as detailed in the solubility data. Its chemical structure containing an acrylamide warhead indicates that it acts as a covalent inhibitor, potentially leading to a long residence time on its target in vivo.
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| Toxicity/Toxicokinetics |
Specific toxicology data for MS117 is not presented. The compound is a research tool for studying PRMT6 biology. As a first-in-class covalent inhibitor, its toxicity profile is not fully characterized. The primary focus of its use is to validate PRMT6 as a therapeutic target. While not formally in clinical trials, its use provides proof-of-concept for targeting PRMT6 with covalent inhibitors for therapeutic intervention.
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| References | |
| Additional Infomation |
PRMT6 is an arginine methyltransferase that catalyzes the asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a), which represses transcription. It is overexpressed in several cancers, including bladder, breast, and lung cancers, and is associated with poor patient prognosis. MS117 is the first irreversible covalent inhibitor developed for PRMT6. Its covalent mechanism provides a powerful tool for cellular and in vivo target validation studies in the field of cancer epigenetics.
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| Molecular Formula |
C17H22N4O
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|---|---|
| Molecular Weight |
298.382783412933
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| Exact Mass |
298.179
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| CAS # |
2702280-86-0
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| PubChem CID |
138753329
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| Appearance |
Light brown to brown solid powder
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| LogP |
1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
22
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| Complexity |
374
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(NC1C=C(C2C(CN(CCN)C)=CNC=2)C=CC=1)C=C
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| InChi Key |
HVDMIAFOVVMNJF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H22N4O/c1-3-17(22)20-15-6-4-5-13(9-15)16-11-19-10-14(16)12-21(2)8-7-18/h3-6,9-11,19H,1,7-8,12,18H2,2H3,(H,20,22)
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| Chemical Name |
N-[3-[4-[[2-aminoethyl(methyl)amino]methyl]-1H-pyrrol-3-yl]phenyl]prop-2-enamide
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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) |
DMSO: 100 mg/mL (335.14 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.38 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3514 mL | 16.7572 mL | 33.5143 mL | |
| 5 mM | 0.6703 mL | 3.3514 mL | 6.7029 mL | |
| 10 mM | 0.3351 mL | 1.6757 mL | 3.3514 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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