| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
PEG2000-C-DMG does not have a traditional drug target. Instead, it functions as a surface-modifying excipient in LNPs. The PEG chain creates a hydrophilic "stealth" layer around LNPs, preventing opsonization and recognition by the reticuloendothelial system (RES), thereby prolonging circulation time. Additionally, PEG2000-C-DMG is designed to dissociate from the LNP surface over time, exposing the underlying cationic or ionizable lipids to facilitate cellular uptake.
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| ln Vitro |
In vitro, liposomes containing PEG2000-C-DMG show reduced uptake by cultured cardiomyocytes and other phagocytic cells compared to non-PEGylated formulations. The fixed aqueous layer thickness (FALT) around PEG2000-modified liposomes correlates with prolonged circulation and reduced RES clearance. Liposomes modified with PEG2000 are useful for uptake into tumor cells via passive targeting through the enhanced permeability and retention (EPR) effect.
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| ln Vivo |
In vivo, LNPs containing PEG2000-C-DMG have been used in patisiran, an siRNA therapeutic for hereditary transthyretin-mediated amyloidosis (hATTR), demonstrating effective delivery of siRNA to hepatocytes following intravenous administration. In rats and monkeys, PEG2000-C-DMG is eliminated unchanged in the bile. Intravenous administration of PEG2000-C-DMG-containing LNPs results in prolonged circulation time compared to non-PEGylated counterparts, allowing enhanced accumulation in target tissues.
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| Enzyme Assay |
Binding studies are typically performed to characterize LNP surface properties, not as a traditional receptor binding assay. One method is to measure the fixed aqueous layer thickness (FALT) of PEG2000-C-DMG-modified liposomes by photon correlation spectroscopy or zeta potential measurements. The surface coverage of PEG can be quantified by ¹H-NMR or by using radiolabeled PEG-lipid, where liposomes are separated from unincorporated lipid by size exclusion chromatography or ultracentrifugation. Protein corona formation is assessed by incubating LNPs with serum or plasma (50% v/v, 37degC, 1-4 h), followed by SDS-PAGE and mass spectrometry identification of bound proteins. Complement activation is measured by ELISA for C3a or C5b-9 deposition. Uptake by RAW264.7 macrophages (a model of RES cells) is quantified by flow cytometry using fluorescently labeled LNPs (e.g., DiD or rhodamine-DOPE).
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| Cell Assay |
HepG2 or primary hepatocytes are plated in 24-well plates (1×10⁵ cells/well) and treated with LNPs containing PEG2000-C-DMG and encapsulating fluorescently labeled siRNA (e.g., Cy5-siRNA) at concentrations equivalent to 10-200 nM siRNA. After 4-24 hours of incubation at 37degC, cellular uptake is measured by flow cytometry or confocal microscopy. Gene silencing efficiency is determined by qRT-PCR of the target mRNA (e.g., TTR or GFP). Cytotoxicity is assessed by MTT or CellTiter-Glo assay. Fixed aqueous layer thickness (FALT) can be correlated with uptake efficiency.
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| Animal Protocol |
In animal PK studies, LNPs containing PEG2000-C-DMG and siRNA (e.g., patisiran) are administered intravenously to rats or cynomolgus monkeys at clinically relevant doses (0.1-1 mg/kg siRNA). Blood samples are collected at multiple time points (5 min to 48 hours). Plasma siRNA concentration is quantified by qRT-PCR or hybridization assay. Tissue distribution (liver, spleen, kidney) is determined by homogenization and siRNA quantification. For toxicity studies, animals are dosed once every 3 weeks for up to 24 months. PEG2000-C-DMG pharmacokinetics are derived from total PEG measurement in plasma or from quantification of the DMG metabolite.
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| ADME/Pharmacokinetics |
In humans, following IV administration of patisiran (0.3 mg/kg once every 3 weeks), the estimated steady-state clearance (CLss) of PEG2000-C-DMG is 2.1 +/- 0.6 mL/h/kg, and the half-life is approximately 80-100 hours. In rats and monkeys, PEG2000-C-DMG is eliminated unchanged in the bile, and no parent drug or metabolite is detected in urine. PK is linear and time-independent with chronic dosing. PEG2000-C-DMG shows no drug-drug interactions or CYP450 modulation due to its lipid excipient nature.
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| Toxicity/Toxicokinetics |
Toxicology studies in rats and monkeys demonstrate that PEG2000-C-DMG is well tolerated at the doses used in patisiran (0.3 mg/kg, IV, once every 3 weeks). No significant treatment-related adverse effects are attributed to the PEG2000-C-DMG component itself. The primary safety concern for PEGylated lipids is potential complement activation-related pseudoallergy (CARPA) upon first infusion, which is managed by slow infusion and premedication. In the patisiran clinical trials, infusion-related reactions were the most common adverse event, but these were mild to moderate and manageable.
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| References | |
| Additional Infomation |
PEG2000-C-DMG is a key component of the lipid nanoparticle (LNP) formulation of patisiran (ONPATTRO®), an FDA-approved (2018) and EMA-approved siRNA therapeutic for hereditary transthyretin-mediated amyloidosis (hATTR) with polyneuropathy. The compound's lipid anchor (DMG, C14:0) is relatively short compared to DSPE-PEG (C18:0), allowing it to dissociate from the particle surface more rapidly, which is critical for endosomal release of siRNA. It is also used in other LNP-based therapeutics and vaccines currently in development, including COVID-19 mRNA vaccines. The TFA salt is not relevant for this PEGylated lipid; it is typically supplied as a solid or in chloroform solution.
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| Molecular Formula |
C126H249NO52
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|---|---|
| Molecular Weight |
2610.29
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| Exact Mass |
671.534
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| PubChem CID |
166638297
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
39
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| Heavy Atom Count |
47
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| Complexity |
705
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCCCCCCCCCCCCC(=O)OC[C@H](COC(=O)NCCCOCCOC)OC(=O)CCCCCCCCCCCCC
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| InChi Key |
YWYMLVACUCXAEC-PGUFJCEWSA-N
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| InChi Code |
InChI=1S/C38H73NO8/c1-4-6-8-10-12-14-16-18-20-22-24-27-36(40)45-33-35(34-46-38(42)39-29-26-30-44-32-31-43-3)47-37(41)28-25-23-21-19-17-15-13-11-9-7-5-2/h35H,4-34H2,1-3H3,(H,39,42)/t35-/m1/s1
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| Chemical Name |
[(2R)-3-[3-(2-methoxyethoxy)propylcarbamoyloxy]-2-tetradecanoyloxypropyl] tetradecanoate
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 (~38.31 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (0.96 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 (0.96 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 (0.96 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 | 0.3831 mL | 1.9155 mL | 3.8310 mL | |
| 5 mM | 0.0766 mL | 0.3831 mL | 0.7662 mL | |
| 10 mM | 0.0383 mL | 0.1915 mL | 0.3831 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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