| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
None (excipient). DLin-K-C3-DMA is an ionizable cationic lipid with an amine headgroup that is positively charged at acidic pH (facilitating nucleic acid complexation) and neutral at physiological pH (reducing toxicity). It facilitates endosomal escape via pH-dependent membrane destabilization.
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| ln Vitro |
DLin-K-C3-DMA LNPs efficiently encapsulate siRNA and mRNA, achieving high transfection efficiency in vitro. In HEK293 or HeLa cells, LNPs containing siRNA against a target gene (e.g., luciferase, GFP) demonstrate >90% target gene knockdown at low siRNA concentrations. The ionizable lipid promotes robust endosomal escape, leading to effective RNA interference (RNAi) or protein expression.
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| ln Vivo |
In vivo, DLin-K-C3-DMA LNPs are used for systemic delivery of siRNA to the liver. Following intravenous administration, LNPs accumulate in the liver and mediate efficient gene silencing in hepatocytes. For example, siRNA against apolipoprotein B (ApoB) reduces serum ApoB protein levels by >70%. DLin-K-C3-DMA LNPs have also been used for mRNA delivery, demonstrating robust protein expression in the liver after a single dose.
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| Enzyme Assay |
DLin-K-C3-DMA (C44H₈1NO2, MW 656.12) is dissolved in ethanol at ∼10-25 mg/mL. It is mixed with helper lipids (e.g., DSPC, cholesterol, PEG2000-DMG or PEG2000-DSPE) at optimized molar ratios (e.g., 40-50:10-15:30-40:1-5) and combined with an acidic aqueous buffer (25-50 mM sodium acetate, pH 4-5) containing the nucleic acid (siRNA, mRNA) via rapid mixing or microfluidic mixing. LNPs form spontaneously with sizes of 50-150 nm. Characterization includes DLS (size, PDI), zeta potential (∼+10 to +30 mV at low pH, ∼0 to +10 mV at pH 7.4), encapsulation efficiency (>90%) via Ribogreen or RiboGreen assay, and pKa measurement (typically ∼6.5-7.0).
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| Cell Assay |
For in vitro studies, LNPs are diluted in serum-free medium and added to cells (e.g., HEK293, HeLa, HepG2) at siRNA doses of 1-100 nM or mRNA doses of 0.01-1 ug/well in 96-well plates. After 4-6 h, medium is replaced. Gene knockdown is measured 24-72 h post-transfection by qRT-PCR or Western blotting, or by reporter assays (luciferase, GFP). For mRNA delivery, reporter gene expression is measured by luminescence or flow cytometry. Cytotoxicity is assessed by MTT assays; DLin-K-C3-DMA LNPs show low toxicity at effective doses.
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| Animal Protocol |
For in vivo studies, DLin-K-C3-DMA LNPs are administered intravenously via the tail vein to 6-8 week old female BALB/c or C57BL/6 mice at siRNA doses of 0.1-1 mg/kg or mRNA doses of 0.2-1 mg/kg. Blood samples are collected at various time points (0, 1, 2, 4, 8, 24 h) for PK analysis. For efficacy: tissues (liver, spleen) are harvested 24-72 h post-dose. mRNA or protein levels of the target gene are quantified by qRT-PCR, Western blotting, or ELISA. For mRNA delivery, luciferase activity in liver homogenates or in vivo bioluminescence imaging is performed. Tissues are fixed for histology (H&E staining) to assess safety.
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| ADME/Pharmacokinetics |
Following i.v. administration, DLin-K-C3-DMA LNPs have a plasma circulation half-life of 1-3 hours. LNPs accumulate predominantly in the liver (∼40-60% of injected dose) and spleen (∼10-20%). The lipid is cleared via metabolic degradation: the linoleyl tails (DLin) are unsaturated and susceptible to oxidation; the ester linkage can be hydrolyzed, and the resulting metabolites (fatty acids, DMA headgroup fragments) are eliminated via biliary and renal excretion. The pKa (∼6.5-7.0) allows for efficient endosomal escape.
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| Toxicity/Toxicokinetics |
DLin-K-C3-DMA LNPs are generally well-tolerated at siRNA doses ≤1 mg/kg. Mild, transient elevations of ALT/AST (2-3× baseline) may occur within 6-24 h post-dose, returning to baseline within 48-72 h. No significant histopathological changes have been reported. Cytokine responses (IL-6, TNF-alpha) may be observed but are typically mild. At high doses (>2 mg/kg siRNA), lethargy, piloerection, and more pronounced ALT/AST elevation may occur. The safety profile is similar to other ionizable lipids like DLin-MC3-DMA.
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| References | |
| Additional Infomation |
DLin-K-C3-DMA (CAS 1217306-46-1, C44H₈1NO2, MW 656.1) has >98% purity and is a colorless to light yellow liquid. Storage at -20degC is recommended. DLin-K-C3-DMA is structurally related to DLin-MC3-DMA (the lipid in Onpattro) but contains a shorter (C3) linker and lacks the hydroxyl group. It is for research use only; not approved for human use. No clinical trials have been reported.
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| Molecular Formula |
C44H81NO2
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|---|---|
| Molecular Weight |
656.1195
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| Exact Mass |
655.626
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| CAS # |
1217306-46-1
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| PubChem CID |
58473224
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| Appearance |
Colorless to light yellow liquid
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| LogP |
16
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
34
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| Heavy Atom Count |
47
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| Complexity |
719
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCC/C=C\C/C=C\CCCCCCCCC1(OC(CO1)CCCN(C)C)CCCCCCCC/C=C\C/C=C\CCCCC
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| InChi Key |
HNTKPUXXCNQLFR-KWXKLSQISA-N
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| InChi Code |
InChI=1S/C44H81NO2/c1-5-7-9-11-13-15-17-19-21-23-25-27-29-31-33-35-39-44(46-42-43(47-44)38-37-41-45(3)4)40-36-34-32-30-28-26-24-22-20-18-16-14-12-10-8-6-2/h13-16,19-22,43H,5-12,17-18,23-42H2,1-4H3/b15-13-,16-14-,21-19-,22-20-
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| Chemical Name |
3-[2,2-bis[(9Z,12Z)-octadeca-9,12-dienyl]-1,3-dioxolan-4-yl]-N,N-dimethylpropan-1-amine
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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 (152.41 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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. Solubility in Formulation 2: 2.5 mg/mL (3.81 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5241 mL | 7.6206 mL | 15.2411 mL | |
| 5 mM | 0.3048 mL | 1.5241 mL | 3.0482 mL | |
| 10 mM | 0.1524 mL | 0.7621 mL | 1.5241 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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