Physicochemical Properties
| CAS # | 2783961-86-2 |
| Appearance | Typically exists as solid at room temperature |
| 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 | Compound 41 (PRMT5-IN-19) exhibits a potent anti-proliferative effect on A375 cells, as demonstrated by its IC50 value of 1.36 μM [1]. Compared to other histone methyltransferases (PRMT1 and PRMT4) and PKMTS (EZH2, NSD2, MLL1 and MLL4), PRMT5-IN-19 exhibits higher selectivity for PRMT5 (IC50 value of 23.9 nM) [1]. The SAM binding pocket in PRMT5 is occupied by PRMT5-IN-19 [1]. Several cancer cell lines (A-375, CHL-1, SNU-423, SNU-449, MDA-MB-231, MDA-MA-453, MV-4) of Proliferation-11, MOLM13) are inhibited by PRMT5-IN-19 (4-5 days), with IC50 values ranging from 1.08 to 3.45 μM [1]. In A375 cells, PRMT5-IN-19 inhibits arginine symmetric dimethylation [1]. Apoptosis is induced in a concentration-dependent manner by PRMT5-IN-19 (0–4 μM, 48 h), which inhibits the proliferation of A375 cells [1]. |
| ln Vivo | PRMT5-IN-19 (Compound 41, A375 xenograft model, 75 mg/kg/d, po, 19 days) possesses good PK characteristics and considerable anti-tumor effectiveness without evident body weight loss and visual toxicity [ 1]. |
| Cell Assay |
Cell proliferation assay[1] Cell Types: A-375, CHL-1, SNU-423, SNU-449, MDA-MB-231, MDA-MA-453, MV-4-11, MOLM13 Tested Concentrations: 0-10 μM Incubation Duration: 5 days Experimental Results: Inhibited the proliferation of multiple cancer cell lines with IC50 values ranging from 1.08 to 3.45 μM. Western Blot Analysis[1] Cell Types: A-375 Cell Tested Concentrations: 0.5, 1, 2, 4,8 μM Incubation Duration: 48 hrs (hours). Experimental Results: Inhibition of arginine symmetric dimethylation in a dose-dependent manner. |
| Animal Protocol |
Animal/Disease Models: A375 cell-derived nude mouse xenograft model [1]. Doses: 75 mg/kg/d Doses: Po, 19 days Experimental Results: No effect on body weight, showing anti-tumor efficacy by inhibiting the methyltransferase activity of PRMT5, with a tumor growth inhibition (TGI) rate of 73%. Animal/Disease Models: Rats and mice [1]. Doses: Oral 10 mg/kg, intravenous (iv) (iv)injection 3 mg/kg Route of Administration: po (po (oral gavage)) intravenous (iv) (iv)injection (pharmacokinetic/PK/PK analysis) Experimental Results: pharmacokinetic/PK/PK parameters of PRMT5-IN-19 in SD rats and Micea, c [1]. |
| References | [1]. Deqin Rong, et al. Structure-Aided Design, Synthesis, and Biological Evaluation of Potent and Selective Non-Nucleoside Inhibitors Targeting Protein Arginine Methyltransferase 5. J Med Chem. 2022 Jun 9;65(11):7854-7875. |
Solubility Data
| 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 |
| 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.) |