MS049 (MS 049; MS-049) is a potent and selective inhibitor of protein arginine methyltransferases-PRMT4 and PRMT6 with potential antineoplastic activity. It inhibits PRMT4/6 with IC50s of 34 nM and 43 nM, respectively.
Physicochemical Properties
| Molecular Formula | C₁₅H₂₄N₂O |
| Molecular Weight | 248.36 |
| Exact Mass | 248.188 |
| Elemental Analysis | C, 72.54; H, 9.74; N, 11.28; O, 6.44 |
| CAS # | 1502816-23-0 |
| Related CAS # | MS049 dihydrochloride;2095432-59-8 |
| PubChem CID | 53868701 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.0±0.1 g/cm3 |
| Boiling Point | 352.6±37.0 °C at 760 mmHg |
| Flash Point | 167.0±26.5 °C |
| Vapour Pressure | 0.0±0.8 mmHg at 25°C |
| Index of Refraction | 1.543 |
| LogP | 2.21 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 18 |
| Complexity | 209 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CNCCN1CCC(OCC2=CC=CC=C2)CC1 |
| 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 | N-methyl-2-(4-phenylmethoxypiperidin-1-yl)ethanamine |
| Synonyms | MS 049 MS049MS-049 |
| 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) |
Biological Activity
| ln Vitro | The H3R2me2a mark in HEK293 cells is lowered in a concentration-dependent manner (IC50=0.97±0.05 μM) by MS049 (0.1-10 μM; 20 hours) [1]. In HEK293 cells (Med12-Rme2a, IC50 = 1.4±0.1 μM), MS049 (0.1-100 μM; 72 hours) decreased the amount of endogenous PRMT4 methyltransferase activity, leading to a decrease in cellular asymmetric arginine dimethylation of Med12[1]. In addition to non-epigenetic targets, MS049 is selective for PRMT4 and PRMT6 against a range of epigenetic modifiers, including as other PRMT, PKMT, DNMT, KDM, and methyllysine/methylarginine reader proteins [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: Reduce H3R2me2a mark in HEK293 cells in a concentration-dependent manner (IC50=0.97±0.05 μM). Western Blot Analysis[1] Cell Types: HEK293 Cell Tested Concentrations: 0.1, 1, 10, 100 μM Incubation Duration: 72 hrs (hours) Experimental Results: Cellular asymmetric arginine dimethylation levels of Med12 are diminished (Med12-Rme2a, IC50=1.4 ±0.1 μM) HEK293 cells. |
| References |
[1]. Discovery of a Potent, Selective, and Cell-Active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6. J Med Chem. 2016 Sep 15. |
Solubility Data
| Solubility (In Vitro) |
H2O : ≥ 100 mg/mL (~402.64 mM) DMSO : ≥ 31 mg/mL (~124.82 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.07 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 (10.07 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (10.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. Solubility in Formulation 4: 100 mg/mL (402.64 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0264 mL | 20.1321 mL | 40.2641 mL | |
| 5 mM | 0.8053 mL | 4.0264 mL | 8.0528 mL | |
| 10 mM | 0.4026 mL | 2.0132 mL | 4.0264 mL |