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.

Physicochemical Properties

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	MS049 diHCl; MS-049; MS 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 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].
ln Vivo
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.
Animal Protocol
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 Oct 13;59(19):9124-9139.

Solubility Data

Solubility (In Vitro)

DMSO:56 mg/mL (174.3 mM) Water:56 mg/mL (174.3 mM) Ethanol:50 mg/mL (155.6 mM)

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.