| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Toll-like receptor 3 (TLR3) and TLR7/8. Poly(I:C) is recognized by TLR3, while its potassium salt form is recognized by TLR7/8, mimicking viral double-stranded RNA. This interaction triggers the innate immune response, activating downstream signaling pathways that lead to the production of inflammatory cytokines and type I interferons. As a synthetic dsRNA analog, it serves as a potent pathogen-associated molecular pattern (PAMP) to study immune activation and antiviral defense mechanisms.
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| ln Vitro |
TT3 is used to formulate lipid nanoparticles (LNPs) for mRNA delivery. In vitro studies with LNPs containing TT3 have demonstrated efficient cellular uptake and endosomal escape, leading to high transfection efficiency. Encapsulation of reporter mRNAs results in robust protein expression in various cell lines, with minimal cytotoxicity compared to traditional cationic lipids. The ionizable nature of TT3 enables low toxicity and high potency, as it remains neutral at physiological pH but becomes positively charged in the acidic endosomal environment to facilitate membrane disruption and cargo release.
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| ln Vivo |
In vivo studies of TT3-containing LNPs show effective delivery of mRNA encoding human coagulation Factor IX, inducing sustained Factor IX expression in the plasma of mice after a single administration. These LNPs demonstrated favorable biodistribution, with significant accumulation in the liver, and elicited a robust and durable protein expression profile. The ionizable lipid-based formulation shows a favorable safety profile, with minimal elevation of liver enzymes and inflammatory cytokines, supporting its potential for in vivo gene therapy applications.
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| Enzyme Assay |
TT3 lipid formulations are prepared in organic solvents such as ethanol or DMSO, then combined with other lipids (e.g., DSPC, cholesterol, PEG-lipid) in an acidic buffer to form LNPs via microfluidic mixing. The ionizable lipid is dissolved at a concentration of 10-20 mg/mL in ethanol, then mixed with an aqueous phase at a 1:3 volume ratio using a microfluidic device. The resulting LNPs are dialyzed against PBS to remove ethanol and adjust to neutral pH. Particle size (typically 50-150 nm) and polydispersity are measured by dynamic light scattering (DLS), and encapsulation efficiency is determined using a RiboGreen assay.
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| Cell Assay |
Cells are seeded in 96-well plates at a density of 1×10⁴ to 5×10⁴ cells per well 24 hours before transfection. LNPs containing mRNA or CRISPR/Cas9 components are diluted in Opti-MEM or serum-free medium to a concentration range of 0.1-10 microg/mL and added to cells. After 4-6 hours of incubation, the medium is replaced with complete growth medium. Protein expression is assessed 24-72 hours post-transfection by flow cytometry, Western blot, or luminescence assays. Knockout efficiency for CRISPR/Cas9 is evaluated by T7E1 assay or sequencing 48-72 hours post-transfection. Cell viability is measured using MTT or CellTiter-Glo assays.
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| Animal Protocol |
For in vivo studies, TT3-based LNPs encapsulating mRNA or sgRNA/Cas9 are typically administered intravenously via tail vein injection at doses ranging from 0.5 to 5 mg/kg of total RNA. For mRNA delivery, blood samples are collected at various time points (e.g., 6, 24, 48, 72 hours, and 7 days post-injection) to measure protein expression by ELISA. For tissue distribution, mice are euthanized, and organs (liver, spleen, kidney, lung, heart) are collected for mRNA quantification by qRT-PCR or protein analysis by Western blot. Serum levels of liver enzymes (ALT, AST) and inflammatory cytokines (IL-6, TNF-alpha) are measured to assess hepatotoxicity and immunogenicity.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies of TT3-based LNPs show an elimination half-life of approximately 4-8 hours in circulation, with rapid clearance from the blood and accumulation primarily in the liver (accounting for ~70-80% of the injected dose) due to interaction with ApoE and uptake by hepatocytes via LDL receptors. The LNPs exhibit a multi-phasic clearance pattern: an initial distribution phase (0-2 hours) followed by a slower elimination phase. Tissue concentrations peak within 2-6 hours post-injection, with levels gradually declining over 48-72 hours. Minimal accumulation is observed in the heart and lungs, indicating favorable biodistribution for liver-targeted applications. In vitro release studies show sustained cargo release over 24-48 hours.
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| Toxicity/Toxicokinetics |
TT3-based LNPs generally exhibit a favorable toxicological profile in preclinical studies. Acute toxicity studies in mice at doses up to 5 mg/kg demonstrate no significant mortality or adverse clinical signs. Repeated-dose toxicity studies (e.g., three doses over 7-14 days) show mild, reversible elevations in ALT and AST (1.5-2 fold above baseline) and transient increases in pro-inflammatory cytokines such as IL-6 and TNF-alpha, which typically resolve within 48-72 hours. Histopathological examination reveals minimal to mild vacuolation in liver tissue without evidence of necrosis or fibrosis. No significant hematological abnormalities or organ weight changes are observed. Further safety studies are recommended for chronic dosing regimens.
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| References | |
| Additional Infomation |
TT3 is a research-grade ionizable lipid not yet approved for human therapeutic use. Its primary application is in the formulation of lipid nanoparticles for the delivery of mRNA and CRISPR/Cas9 gene editing systems. Due to its ionizable headgroup and long hydrocarbon tails, it enables efficient nucleic acid encapsulation, promotes endosomal escape, and minimizes toxicity associated with permanently cationic lipids. TT3 is structurally classified as an amino lipid and is typically stored at -20degC to maintain stability. It is available in quantities ranging from 1 mg to larger custom sizes and is intended for laboratory research use only, not for clinical administration.
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| Molecular Formula |
C90H174N6O3
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|---|---|
| Molecular Weight |
1388.38298749924
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| Exact Mass |
1387.364
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| CAS # |
1821214-50-9
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| Related CAS # |
N1,N3,N5-Tris(4-dodecylhexadecyl)benzene-1,3,5-tricarboxamide;2922283-38-1
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| PubChem CID |
122388678
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| Appearance |
Light yellow to yellow ointment
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| LogP |
34.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
81
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| Heavy Atom Count |
99
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| Complexity |
1380
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KIOSQLHXJYTPDN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C90H174N6O3/c1-7-13-19-25-31-37-43-49-55-61-73-94(74-62-56-50-44-38-32-26-20-14-8-2)79-67-70-91-88(97)85-82-86(89(98)92-71-68-80-95(75-63-57-51-45-39-33-27-21-15-9-3)76-64-58-52-46-40-34-28-22-16-10-4)84-87(83-85)90(99)93-72-69-81-96(77-65-59-53-47-41-35-29-23-17-11-5)78-66-60-54-48-42-36-30-24-18-12-6/h82-84H,7-81H2,1-6H3,(H,91,97)(H,92,98)(H,93,99)
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| Chemical Name |
1-N,3-N,5-N-tris[3-(didodecylamino)propyl]benzene-1,3,5-tricarboxamide
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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 (~72.03 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (1.80 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 (1.80 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 (1.80 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 | 0.7203 mL | 3.6013 mL | 7.2026 mL | |
| 5 mM | 0.1441 mL | 0.7203 mL | 1.4405 mL | |
| 10 mM | 0.0720 mL | 0.3601 mL | 0.7203 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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