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| Targets |
The primary targets of 4A3-SC8 are not biological receptors but rather the siRNA or RNA payload it delivers. As a delivery vehicle, it enables the encapsulation and intracellular delivery of RNA therapeutics. It is designed to facilitate the accumulation of siRNA in the liver, spleen, and kidneys following intravenous administration.
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| ln Vitro |
In vitro, 4A3-SC8 functions as a lipid nanoparticle (LNP) component for RNA delivery. It encapsulates siRNA, protecting it from degradation and facilitating its cellular uptake. This leads to the effective silencing of target genes, such as Factor VII (FVII), in cell-based assays.
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| ln Vivo |
In mice injected intravenously with 1 mg siRNA/kg for 24 hours, 4A3-SC8 promotes siRNA accumulation primarily in the liver and a minor amount in the spleen and kidney, and it inhibits >95% of FVII [1]. On the first day following injection, mice receiving 100 mg/kg of 4A3-SC8 (together with 4 mg/kg of control siRNA siCTR) experienced illness and lost close to 20% of their body weight [1].
In vivo, 4A3-SC8-containing LNPs mediate siRNA accumulation mainly in the liver, with some accumulation in the spleen and kidneys, 24 hours after intravenous injection. This targeted delivery enables potent gene silencing, achieving >95% knockdown of hepatic Factor VII in mice. |
| Enzyme Assay |
Non-cellular assays for 4A3-SC8 typically involve characterizing its physicochemical properties, such as particle size, zeta potential, and encapsulation efficiency. These assays are used to optimize LNP formulations and ensure consistent quality for in vitro and in vivo studies.
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| Cell Assay |
Cellular assays for 4A3-SC8 are conducted using cell lines to assess siRNA delivery efficiency and gene silencing. Cells are treated with 4A3-SC8/siRNA complexes, and target gene expression is measured by qPCR or Western blotting. Cell viability is assessed to determine cytotoxicity.
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| Animal Protocol |
In vivo animal experiments for 4A3-SC8 typically use mouse models. The compound is administered via intravenous injection, and its biodistribution is assessed by measuring siRNA accumulation in various organs. Gene silencing efficacy is evaluated by measuring target gene expression (e.g., FVII) in the liver.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of 4A3-SC8 are related to its role as a drug delivery vehicle. Following intravenous injection, the LNPs facilitate the rapid accumulation of siRNA in target organs, such as the liver. The dendrimer is designed to be degradable, which may enhance its clearance and safety profile.
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| Toxicity/Toxicokinetics |
Toxicological data for 4A3-SC8 are limited, as it is a research reagent. Studies have shown that it is well-tolerated in mice at the doses used for siRNA delivery. Standard laboratory safety precautions should be followed when handling the compound.
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| References | |
| Additional Infomation |
4A3-SC8 is an innovative, modular degradable dendrimer for RNA delivery. It is used to synthesize lipid nanoparticles (LNPs) for the encapsulation of siRNA. It has shown promise in extending survival in aggressive liver cancer models and is a valuable tool for gene regulation studies.
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| Molecular Formula |
C75H139N3O16S4
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|---|---|
| Molecular Weight |
1467.18
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| Exact Mass |
1465.903
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| CAS # |
1857340-78-3
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| PubChem CID |
129092706
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| Appearance |
Colorless to light yellow liquid
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| LogP |
18.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
23
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| Rotatable Bond Count |
80
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| Heavy Atom Count |
98
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| Complexity |
1730
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCCCCCSCC(C)C(=O)OCCOC(=O)CCN(CCCN(C)CCCN(CCC(=O)OCCOC(=O)C(C)CSCCCCCCCC)CCC(=O)OCCOC(=O)C(C)CSCCCCCCCC)CCC(=O)OCCOC(=O)C(C)CSCCCCCCCC
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| InChi Key |
HMIDEMNFLBUNTB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C75H139N3O16S4/c1-10-14-18-22-26-30-56-95-60-64(5)72(83)91-52-48-87-68(79)36-44-77(45-37-69(80)88-49-53-92-73(84)65(6)61-96-57-31-27-23-19-15-11-2)42-34-40-76(9)41-35-43-78(46-38-70(81)89-50-54-93-74(85)66(7)62-97-58-32-28-24-20-16-12-3)47-39-71(82)90-51-55-94-75(86)67(8)63-98-59-33-29-25-21-17-13-4/h64-67H,10-63H2,1-9H3
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| Chemical Name |
2-[3-[3-[3-[bis[3-[2-(2-methyl-3-octylsulfanylpropanoyl)oxyethoxy]-3-oxopropyl]amino]propyl-methylamino]propyl-[3-[2-(2-methyl-3-octylsulfanylpropanoyl)oxyethoxy]-3-oxopropyl]amino]propanoyloxy]ethyl 2-methyl-3-octylsulfanylpropanoate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ≥ 100 mg/mL (68.16 mM)
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|---|---|
| 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 | 0.6816 mL | 3.4079 mL | 6.8158 mL | |
| 5 mM | 0.1363 mL | 0.6816 mL | 1.3632 mL | |
| 10 mM | 0.0682 mL | 0.3408 mL | 0.6816 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.
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