| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The target of OF-C4-Deg-Lin is not a biological molecule, but rather the delivery vehicle itself. It is a functional excipient used to form lipid nanoparticles (LNPs). These LNPs target the endosomal pathway within cells. Once the LNP is endocytosed, the ionizable lipid helps to destabilize the endosomal membrane, facilitating the release of the encapsulated siRNA or mRNA payload into the cytoplasm.
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|---|---|
| ln Vitro |
OF-C4-Deg-Lin is an ionizable lipid with varying linker lengths. Its "activity" is measured by its ability to encapsulate nucleic acids (siRNA, mRNA) into stable LNPs and to facilitate the transfection of these payloads into cells in vitro. In cell culture studies, LNPs formulated with OF-C4-Deg-Lin demonstrate efficient gene silencing (for siRNA) or protein expression (for mRNA) with low cytotoxicity compared to non-degradable counterparts.
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| ln Vivo |
OF-C4-Deg-Lin has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA and mRNA in vivo. In animal models (e.g., mice), LNPs containing OF-C4-Deg-Lin have been shown to effectively deliver siRNA to the liver (after intravenous administration) to silence target genes, or to deliver mRNA for the production of therapeutic proteins such as Cas9 for gene editing or antigens for vaccines. The degradable linker is designed to enhance clearance and reduce accumulation.
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| Enzyme Assay |
Not applicable (no enzyme target). The characterization of OF-C4-Deg-Lin is performed using physicochemical assays rather than biological binding assays. Key parameters include: the critical micelle concentration (CMC), particle size (dynamic light scattering, DLS), polydispersity index (PDI), zeta potential, and the efficiency of nucleic acid encapsulation (using a RiboGreen assay or similar). The pKa of the ionizable lipid is also measured to determine its protonation behavior at physiological pH.
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| Cell Assay |
To assess OF-C4-Deg-Lin in vitro, LNPs encapsulating a reporter mRNA (e.g., encoding luciferase or GFP) or a therapeutic siRNA (e.g., targeting GFP or a housekeeping gene) are prepared. Cells (e.g., HeLa, HEK293T, or primary hepatocytes) are treated with the LNP formulations. For mRNA delivery, efficacy is measured by luminescence (luciferase), fluorescence microscopy (GFP), or ELISA (for a secreted protein). For siRNA delivery, efficacy is measured by qPCR or Western blot to quantify the reduction in target gene mRNA or protein levels. Cytotoxicity is assessed by MTT or ATP assays.
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| Animal Protocol |
The in vivo efficacy of OF-C4-Deg-Lin is tested in animal models. For siRNA delivery, mice are administered LNPs (containing siRNA against a liver-specific gene, like Factor VII or TTR) via intravenous (IV) injection. Blood is collected at various time points, and the protein levels of the target (e.g., Factor VII) are measured to determine the degree of gene silencing. For mRNA delivery, LNPs encapsulating a reporter mRNA (luciferase) are injected IV, and in vivo bioluminescence imaging is used to measure protein expression in the liver. Tissues are collected to assess the distribution of the payload and the lipid itself.
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| ADME/Pharmacokinetics |
OF-C4-Deg-Lin is an ionizable lipid with a molecular weight of 1594.49 and a molecular formula of C100H176N4O10. It is soluble in ethanol (≥45.8 mg/mL) but insoluble in water and DMSO. For LNP formulation, it is combined with other lipids (e.g., DSPC, cholesterol, and PEG-lipid) in an organic solvent, which is then mixed with an aqueous solution of nucleic acid using microfluidic mixing. The LNPs are characterized for size, polydispersity, and encapsulation efficiency. The degradable linker is designed to facilitate the in vivo clearance of the lipid.
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| Toxicity/Toxicokinetics |
The toxicity of OF-C4-Deg-Lin is a critical parameter, as LNPs can cause dose-limiting hepatotoxicity. The degradable linker in OF-C4-Deg-Lin is specifically designed to be hydrolyzed in vivo, leading to the generation of less toxic metabolites and reducing the potential for lipid accumulation in tissues. In standard in vivo studies, toxicity endpoints include body weight loss, serum biomarkers of liver injury (ALT, AST), and histological examination of the liver and spleen. OF-C4-Deg-Lin is part of a class of "next-generation" biodegradable ionizable lipids intended to have an improved safety profile over first-generation lipids.
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| References | |
| Additional Infomation |
OF-C4-Deg-Lin is a research-grade, ionizable lipid used in the formulation of lipid nanoparticles (LNPs) for nucleic acid delivery. It is part of a series of "OF-C4-Deg" lipids with varying linker lengths, designed to optimize delivery and biodegradability. This compound is not a therapeutic agent but an excipient. The development of such ionizable lipids was crucial for the success of RNA-based therapeutics, including the mRNA COVID-19 vaccines and siRNA drugs like patisiran (Onpattro). OF-C4-Deg-Lin is exclusively for preclinical research to develop new LNP formulations for gene therapy, protein replacement therapy, and vaccines. It is not an approved drug, and is not for human use.
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| Molecular Formula |
C100H176N4O10
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|---|---|
| Molecular Weight |
1594.48827171326
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| Exact Mass |
1594.342
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| CAS # |
2383003-60-7
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| PubChem CID |
168006879
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| Appearance |
Colorless to light yellow viscous liquid
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| LogP |
30.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
90
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| Heavy Atom Count |
114
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| Complexity |
2160
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CCCCC/C=C\C/C=C\CCCCCCCC(=O)OCCCCN(CCCCOC(=O)CCCCCCC/C=C\C/C=C\CCCCC)CCCC[C@@H]1NC(=O)[C@@H](NC1=O)CCCCN(CCCCOC(=O)CCCCCCC/C=C\C/C=C\CCCCC)CCCCOC(=O)CCCCCCC/C=C\C/C=C\CCCCC
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| InChi Key |
ZQXDXCNSODVUPG-ACIWIILCSA-N
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| InChi Code |
InChI=1S/C100H176N4O10/c1-5-9-13-17-21-25-29-33-37-41-45-49-53-57-61-79-95(105)111-89-73-69-85-103(86-70-74-90-112-96(106)80-62-58-54-50-46-42-38-34-30-26-22-18-14-10-6-2)83-67-65-77-93-99(109)102-94(100(110)101-93)78-66-68-84-104(87-71-75-91-113-97(107)81-63-59-55-51-47-43-39-35-31-27-23-19-15-11-7-3)88-72-76-92-114-98(108)82-64-60-56-52-48-44-40-36-32-28-24-20-16-12-8-4/h21-28,33-40,93-94H,5-20,29-32,41-92H2,1-4H3,(H,101,110)(H,102,109)/b25-21-,26-22-,27-23-,28-24-,37-33-,38-34-,39-35-,40-36-/t93-,94-/m0/s1
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| Chemical Name |
4-[4-[(2S,5S)-5-[4-[bis[4-[(9Z,12Z)-octadeca-9,12-dienoyl]oxybutyl]amino]butyl]-3,6-dioxopiperazin-2-yl]butyl-[4-[(9Z,12Z)-octadeca-9,12-dienoyl]oxybutyl]amino]butyl (9Z,12Z)-octadeca-9,12-dienoate
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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 |
| 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 (62.72 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (1.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6272 mL | 3.1358 mL | 6.2716 mL | |
| 5 mM | 0.1254 mL | 0.6272 mL | 1.2543 mL | |
| 10 mM | 0.0627 mL | 0.3136 mL | 0.6272 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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