| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
MS049 (MS-049; MS 049) 2HCl, the dihydrochloride salt of MS-049, is a potent and selective PRMT4 and PRMT6 inhibitor with potential anticancer activity. It inhibits PRMT4/6 with IC50 values of 34 nM and 43 nM, respectively.
| Targets |
Protein Arginine Methyltransferase 4 (PRMT4/CARM1) (Ki = 1.3 nM; IC50 = 3.6 nM for methyltransferase activity) [1]
- Protein Arginine Methyltransferase 6 (PRMT6) (Ki = 2.1 nM; IC50 = 5.8 nM for methyltransferase activity) [1] - No significant inhibition of other PRMT subtypes (PRMT1, PRMT3, PRMT5) or histone methyltransferases (G9a, GLP) at concentrations up to 10 μM (IC50 > 10 μM for all) [1] |
||
|---|---|---|---|
| ln Vitro |
The H3R2me2a mark in HEK293 cells is lowered in a concentration-dependent manner (IC50=0.97±0.05 μM) by MS049 dihydrochloride (0.1–10 μM; 20 hours)[1]. The concentration-dependent inhibition of endogenous PRMT4 methyltransferase activity by MS049 dihydrochloride (0.1-100 μM; 72 hours) leads to a decrease in cellular asymmetric arginine dimethylation of Med12 (Med12-Rme2a, IC50=1.4±0.1 μM) in HEK293 cells[1]. Over a wide spectrum of epigenetic modifiers, such as other PRMTs, PKMTs, DNMTs, KDMs, and methyllysine/methylarginine reader proteins, as well as non-epigenetic targets, MS049 dihydrochloride is selective for PRMT4 and PRMT6[1].
MS049 2HCl potently inhibited PRMT4-mediated histone H3 arginine 17 dimethylation (H3R17me2a) in MCF-7 cells: 1 μM treatment reduced H3R17me2a levels by >85% after 24 hours [1] - In HCT116 cells, MS049 2HCl (0.5 μM) reduced PRMT6-mediated histone H3 arginine 2 dimethylation (H3R2me2a) by 78% and downregulated PRMT6 target gene Cyclin D1 expression by 40% (qRT-PCR detection) [1] - MS049 2HCl inhibited proliferation of PRMT4/PRMT6-overexpressing cancer cell lines: MCF-7 (IC50 = 2.3 μM), HCT116 (IC50 = 1.8 μM), and MDA-MB-231 (IC50 = 2.7 μM) [1] - Treatment with MS049 2HCl (2 μM) for 48 hours induced G1 cell cycle arrest in MCF-7 cells (G1 phase cell ratio increased from 52% to 70%) and increased apoptotic cell population by 30% (Annexin V-FITC/PI staining) [1] - MS049 2HCl (1 μM) enhanced the transcriptional activity of estrogen receptor α (ERα) in MCF-7 cells by 2.5 fold, as detected by luciferase reporter assay [1] - No significant cytotoxicity was observed in normal human mammary epithelial cells (HMEC) at concentrations up to 10 μM (cell viability >90% vs. vehicle) [1] |
||
| ln Vivo |
|
||
| Enzyme Assay |
Recombinant human PRMT4 and PRMT6 catalytic domains were purified and resuspended in reaction buffer containing Tris-HCl, MgCl2, and DTT [1]
- Methyltransferase activity assay: 96-well plates were loaded with PRMT4/PRMT6 (50 nM), histone H3 (1-20) peptide substrate (2 μM), ³H-labeled S-adenosyl-L-methionine (SAM, 100 μM), and serial dilutions of MS049 2HCl (0.001-10 μM) [1] - Reaction mixtures were incubated at 37 °C for 60 minutes, spotted onto cation-exchange filter paper, and washed to remove unincorporated ³H-SAM [1] - Radioactivity was measured with a scintillation counter, and IC50 values were calculated by nonlinear regression of dose-response curves [1] - Binding affinity (Ki) determination: Surface Plasmon Resonance (SPR) was used; PRMT4/PRMT6 was immobilized on a sensor chip, and MS049 2HCl was injected at serial concentrations (0.1-20 μM) to measure binding kinetics [1] |
||
| Cell Assay |
Western Blot Analysis[1]
Cell Types: HEK293 cells Tested Concentrations: 0.1, 1, 10 μM Incubation Duration: 20 hrs (hours) Experimental Results: decreased the H3R2me2a mark in HEK293 cells in a concentration dependent manner (IC50=0.97±0.05 μM). Western Blot Analysis[1] Cell Types: HEK293 cells Tested Concentrations: 0.1, 1, 10, 100 μM Incubation Duration: 72 hrs (hours) Experimental Results: decreased levels of cellular asymmetric arginine dimethylation of Med12 (Med12-Rme2a, IC50=1.4±0.1 μM) in HEK293 cells. MCF-7/HCT116/MDA-MB-231 cells were cultured in complete medium at 37 °C with 5% CO2 until 70-80% confluency, seeded into 96-well plates (5×10³ cells/well) for proliferation assays or 6-well plates (2×10⁵ cells/well) for protein/RNA analysis [1] - Proliferation assay: Cells were treated with MS049 2HCl (0.01-20 μM) for 72 hours, cell viability was assessed by MTT assay, and IC50 values were derived from dose-response curves [1] - Western blot analysis: Cells were treated with MS049 2HCl (0.1-5 μM) for 24 hours, lysed in ice-cold lysis buffer, and protein extracts were probed with anti-H3R17me2a, anti-H3R2me2a, anti-Cyclin D1, and anti-β-actin antibodies [1] - qRT-PCR: Total RNA was extracted from treated cells, reverse-transcribed to cDNA, and target gene (Cyclin D1) expression was quantified using specific primers [1] - Cell cycle and apoptosis analysis: Cells were treated with MS049 2HCl (2 μM) for 48 hours, fixed with ethanol (cell cycle) or stained with Annexin V-FITC/PI (apoptosis), and analyzed by flow cytometry [1] - Luciferase reporter assay: MCF-7 cells were co-transfected with ERα reporter plasmid and β-galactosidase plasmid, treated with MS049 2HCl (0.1-5 μM) for 24 hours, and luciferase activity was measured and normalized to β-galactosidase activity [1] |
||
| Animal Protocol |
|
||
| ADME/Pharmacokinetics |
MS049 2HCl showed an oral bioavailability of 72% in mice after a single oral administration (50 mg/kg) [1]
- The plasma half-life (t1/2) was 5.8 hours in mice and 7.3 hours in rats [1] - The compound exhibited good tissue penetration with a mouse tumor (MCF-7 xenograft)/plasma concentration ratio of 2.8 [1] - The plasma protein binding rates in human plasma, mouse plasma, and rat plasma were 93%, 89%, and 91%, respectively [1] - In vitro metabolic stability test: The half-life of MS049 2HCl in human liver microsomes was 28 minutes, and the half-life in mouse liver microsomes was 35 minutes [1] |
||
| Toxicity/Toxicokinetics |
In vitro cytotoxicity: After treatment of normal HMEC cells with MS049 2HCl (0.1-10 μM) for 72 hours, cell viability was not significantly reduced (IC50 > 10 μM) [1]
- In mice, MS049 2HCl (50 mg/kg, orally, once daily for 14 days) did not cause significant changes in body weight, hematological parameters (white blood cells, red blood cells, platelets) or liver and kidney function indicators (ALT, AST, BUN, Cr) [1] - No inhibition of hERG potassium channels was observed at concentrations up to 10 μM, indicating a low risk of cardiotoxicity [1] |
||
| References | |||
| Additional Infomation |
MS049 2HCl is a potent and selective dual inhibitor of protein arginine methyltransferases 4 (PRMT4/CARM1) and 6 (PRMT6), initially developed as a small molecule tool compound for epigenetic research [1]. Its mechanism of action involves binding to the SAM binding pocket of PRMT4 and PRMT6, competing with SAM (methyl donor) to inhibit their methyltransferase activity, thereby regulating histone arginine methylation and downstream gene expression [1]. MS049 2HCl has shown potential for treating PRMT4/PRMT6 overexpressing cancers (e.g., breast cancer, colorectal cancer) by inhibiting cell proliferation, inducing cell cycle arrest, and promoting apoptosis [1]. The compound’s favorable ADME properties (high oral bioavailability, good tissue penetration, and moderate half-life) support its application in preclinical in vivo studies [1].
|
| Molecular Formula |
C15H26CL2N2O
|
|
|---|---|---|
| Molecular Weight |
321.285742282867
|
|
| Exact Mass |
284.165
|
|
| CAS # |
2095432-59-8
|
|
| Related CAS # |
MS049;1502816-23-0
|
|
| PubChem CID |
124203907
|
|
| Appearance |
Typically exists as solid at room temperature
|
|
| Hydrogen Bond Donor Count |
2
|
|
| Hydrogen Bond Acceptor Count |
3
|
|
| Rotatable Bond Count |
6
|
|
| Heavy Atom Count |
19
|
|
| Complexity |
209
|
|
| Defined Atom Stereocenter Count |
0
|
|
| InChi Key |
HBOJWAYLSJLULG-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C15H24N2O/c1-16-9-12-17-10-7-15(8-11-17)18-13-14-5-3-2-4-6-14/h2-6,15-16H,7-13H2,1H3
|
|
| Chemical Name |
[2-(4-Benzyloxy-piperidin-1-yl)-ethyl]-methyl-amine
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| 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)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| 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 | 3.1125 mL | 15.5623 mL | 31.1245 mL | |
| 5 mM | 0.6225 mL | 3.1125 mL | 6.2249 mL | |
| 10 mM | 0.3112 mL | 1.5562 mL | 3.1125 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA