Physicochemical Properties
| CAS # | 2091332-22-6 |
| Appearance | Typically exists as solids at room temperature |
| Synonyms | ISIS-484137; ISIS 484137; ION224; ION-224 |
| 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
| Targets | Diacylglycerol O - acyltransferase 2 (DGAT2). |
| ln Vivo | In a 51 - week, multicenter, randomized, double - blind, placebo - controlled phase 2 trial, 160 patients with fibrotic metabolic dysfunction - associated steatohepatitis (MASH) were randomly assigned to receive IONIS - DGAT 2Rx (ION - 224) at doses of 60 mg, 90 mg, 120 mg or placebo. The results showed that the 90 - mg and 120 - mg dose groups had 46% and 59% of patients achieving the primary endpoint (NASH Activity Score (NAS) decreased by ≥2 points and no fibrosis deterioration), significantly higher than 19% in the placebo group. This indicates that IONIS - DGAT 2Rx (ION - 224) can effectively improve the pathological characteristics of MASH by inhibiting DGAT2, and the curative effect is independent of weight change. |
| Animal Protocol | The study was conducted in 43 clinical centers in the United States and Puerto Rico. From June 8, 2021, to December 27, 2022, 160 participants were randomly grouped (23 cases in the 60 - mg group, 45 cases in the 90 - mg group, 46 cases in the 120 - mg group, and 46 cases in the placebo group). IONIS - DGAT 2Rx (ION - 224) was administered without specifying the dissolution formula, and the administration route was not mentioned, but it can be inferred to be a common injection route according to the characteristics of antisense oligonucleotide drugs, and the administration frequency was once every 51 weeks. |
| Toxicity/Toxicokinetics | IONIS - DGAT 2Rx (ION - 224) was well - tolerated, and no serious adverse reactions occurred. The incidence of adverse events was 94% (107/114) in the IONIS - DGAT 2Rx (ION - 224) group and 89% (41/46) in the placebo group. |
| References |
[1]. The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7. Cardiovasc Diabetol. 2024 Jan 9;23(1):21. |
| Additional Infomation | IONIS - DGAT 2Rx (ION - 224) is an antisense oligonucleotide drug developed by using ligand - conjugated antisense (LICA) technology. DGAT2 is an enzyme that catalyzes the last step of triglyceride synthesis in the liver. Reducing the production of DGAT2 will correspondingly reduce the synthesis of triglycerides. There is evidence that the antisense inhibition of DGAT2 is related to the increase of fatty acid oxidation and oxidative gene expression. |
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.) |