| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
DLin-KC2-DMA is an ionizable cationic lipid component of lipid nanoparticles (LNPs) for siRNA delivery, not a drug with specific molecular targets. [1][2]
DLin-KC2-DMA is an ionizable cationic lipid (pKa≈6) that produces significant siRNA-mediated gene silencing of GAPDH when incorporated into LNPs. It is used for siRNA delivery in pharmaceutical and biomedical research. The compound's ionizable amine headgroup enables strong nucleic acid complexation and triggered release under acidic conditions. |
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| ln Vitro |
Significant siRNA-mediated GAPDH gene silencing in macrophages and dendritic cells can be achieved with DLin-KC2-DMA (1, 5 μg; 72 hours) [1]. Dendritic cells and macrophages have a high uptake of DLin-KC2-DMA (24 h) [1]. Following uptake via the endocytic pathway, DLin-KC2-DMA has the ability to efficiently stimulate the release of siRNA that has been encapsulated into the cytosol [1]. In primary APCs, DLin-KC2-DMA is essentially non-toxic [1].
In primary bone marrow-derived dendritic cells (BMDCs), LNPs containing DLin-KC2-DMA achieved 80% silencing of GAPDH mRNA at 100 nM siRNA concentration, significantly outperforming LNPs with other cationic lipids (e.g., DLinDMA: 40% silencing). Silencing efficiency was confirmed by qRT-PCR and correlated with enhanced cellular uptake (flow cytometry). [1] In vitro, DLin-KC2-DMA-formulated LNPs demonstrate efficient cellular uptake and endosomal escape, leading to potent gene silencing. The compound shows similar potency to DLin-MC3-DMA in facilitating siRNA-mediated knockdown of target genes in cell culture. Its pKa of approximately 6.7 is optimal for endosomal escape while maintaining stability in the bloodstream. |
| ln Vivo |
Target genes in APc can be efficiently silenced in vivo by the DLin-KC2-DMA containing LNP siRNA system (5 mg/kg; intravenous injection; single dose) [1].
In vivo, administration of Factor VII siRNA in DLin-KC2-DMA-containing LNPs reduces serum Factor VII protein levels in mice. The compound demonstrates significant in vivo gene silencing efficacy, comparable to the clinically validated DLin-MC3-DMA. DLin-KC2-DMA-based LNPs effectively deliver siRNA to hepatocytes and achieve durable target gene knockdown in rodent models. |
| Enzyme Assay |
In vitro assays for DLin-KC2-DMA involve formulating LNPs with siRNA and characterizing particle size and zeta potential. The ability of DLin-KC2-DMA-based LNPs to facilitate siRNA delivery is assessed in cell culture using reporter gene systems. Gene silencing potency is quantified by measuring IC50 values for target gene knockdown. Endosomal escape is evaluated using fluorescently labeled siRNA and confocal microscopy.
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| Cell Assay |
Cytotoxicity assay [1]
Cell Types: macrophages, dendritic cells Tested Concentrations: 5 μg/mL (DLin-KC2-DMA contains-LNPs) Incubation Duration: 72 h Experimental Results: Almost no toxicity. Western Blot Analysis[1] Cell Types: macrophages, dendritic cells Tested Concentrations: 1, 5 μg Incubation Duration: 72 hrs (hours) Experimental Results: In macrophages, GAPDH silencing exceeded 60% at 1 μg and over 80 at 5 μg %. Dramatically diminished GAPDH protein, showing 83% silencing effect at 5 μg. siRNA transfection efficiency: BMDCs were incubated with DLin-KC2-DMA-based LNPs encapsulating GAPDH siRNA (50-100 nM) for 48h. Cells were lysed for mRNA extraction and qRT-PCR analysis of GAPDH expression. Cellular uptake: BMDCs treated with Cy5-labeled siRNA-loaded LNPs for 4h. Uptake quantified by flow cytometry measuring Cy5 fluorescence intensity. [1] Cellular uptake and gene silencing studies are performed using cell lines such as HepG2 or primary hepatocytes. Cells are treated with DLin-KC2-DMA-formulated LNPs containing siRNA. After incubation, gene expression is measured by qRT-PCR or Western blot. Cytotoxicity is assessed to ensure specificity. Time-course experiments determine the duration of silencing and optimal dosing schedules. |
| Animal Protocol |
Animal/Disease Models: naive C57BL/6 mice[1].
Doses: 3 or 5 mg/kg (DLin-KC2-DMA contains LNP) Route of Administration: Intravenous; single. Experimental Results: GAPDH production was Dramatically diminished in peritoneal macrophages and dendritic cells as well as spleen-derived APCs at the 5 mg/kg dose. In vivo animal studies for DLin-KC2-DMA involve intravenous administration of LNP-formulated siRNA to mice. Gene silencing efficacy is assessed by measuring target protein levels (e.g., Factor VII, TTR) in serum at various time points. Tissue distribution is evaluated by quantifying siRNA and lipid levels in liver, spleen, and other organs. Dose-response studies determine the ED50 for gene silencing. Duration of silencing is monitored over several weeks. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of DLin-KC2-DMA are characteristic of ionizable cationic lipids with ether-linked hydrophobic tails. Following intravenous administration, the compound accumulates primarily in the liver. It has a favorable pharmacokinetic profile with good bioavailability in target tissues. Clearance occurs via hepatic metabolism, with metabolites excreted in bile and urine. The pKa of 6.7 contributes to optimal endosomal escape and intracellular delivery.
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| Toxicity/Toxicokinetics |
DLin-KC2-DMA-LNPs (100 nM siRNA) showed extremely low cytotoxicity to bone marrow-derived dendritic cells (BMDCs), with cell viability >90% (MTT assay). [1]
Toxicological profile of DLin-KC2-DMA is favorable in preclinical studies. The compound shows low cytotoxicity in cell culture and is well-tolerated in vivo at therapeutic doses. Transient increases in liver enzymes may occur at higher doses but are reversible. No significant immunogenicity or off-target effects have been reported. The compound's safety profile supports its use in research applications. |
| References | |
| Additional Infomation |
DLin-KC2-DMA is an optimized ionizable lipid that enables efficient endosome escape of siRNA via pH-dependent charge conversion. [1]
Compared to earlier generations of products (such as DLinDMA-LNP), it facilitates the construction of a “MC3” LNP system with higher potency and lower immunogenicity. [2] DLin-KC2-DMA is an important reference compound in studies of lipid nanoparticle architecture and performance. It represents an intermediate development between the prototypical DLinDMA and the clinically validated DLin-MC3-DMA. DLin-KC2-DMA is widely used in research to optimize LNP formulations for nucleic acid delivery and to study the relationship between lipid structure and delivery efficacy. |
| Molecular Formula |
C43H79NO2
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|---|---|
| Molecular Weight |
642.092873811722
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| Exact Mass |
641.611
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| Elemental Analysis |
C, 80.43; H, 12.40; N, 2.18; O, 4.98
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| CAS # |
1190197-97-7
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| Related CAS # |
1224373-32-3 (S-isomer);1224373-36-7 (R-isomer);1190197-97-7;
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| PubChem CID |
44464860
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| Appearance |
Colorless to light yellow liquid
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| LogP |
15.7
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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 |
33
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| Heavy Atom Count |
46
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| Complexity |
704
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCC/C=C\C/C=C\CCCCCCCCC1(OC(CO1)CCN(C)C)CCCCCCCC/C=C\C/C=C\CCCCC
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| InChi Key |
LRFJOIPOPUJUMI-KWXKLSQISA-N
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| InChi Code |
InChI=1S/C43H79NO2/c1-5-7-9-11-13-15-17-19-21-23-25-27-29-31-33-35-38-43(45-41-42(46-43)37-40-44(3)4)39-36-34-32-30-28-26-24-22-20-18-16-14-12-10-8-6-2/h13-16,19-22,42H,5-12,17-18,23-41H2,1-4H3/b15-13-,16-14-,21-19-,22-20-
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| Chemical Name |
2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane
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| Synonyms |
KC 2 KC-2 KC2; DLin-KC2-DMA; 1190197-97-7; 2-(2,2-Di((9Z,12Z)-octadeca-9,12-dien-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylethanamine; 2-[2,2-bis[(9Z,12Z)-octadeca-9,12-dienyl]-1,3-dioxolan-4-yl]-N,N-dimethylethanamine; 2-[2,2-Di[(9Z,12Z)-octadeca-9,12-dien-1-yl]-1,3-dioxolan-4-yl]-N,N-dimethylethanamine; DLin-KC2-DMA?; SCHEMBL29670; 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane;
DLin-KC2-DMA D-Lin-KC2-DMA
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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: (1). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. (2). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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 (~155.74 mM)
Ethanol : ~100 mg/mL (~155.74 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.89 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 (3.89 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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 (3.89 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 | 1.5574 mL | 7.7871 mL | 15.5741 mL | |
| 5 mM | 0.3115 mL | 1.5574 mL | 3.1148 mL | |
| 10 mM | 0.1557 mL | 0.7787 mL | 1.5574 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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