| Identification | Back Directory | [Name]
Decanoic acid, 2-hexyl-, 1,1'-[[(4-hydroxybutyl)imino]di-6,1-hexanediyl] ester | [CAS]
2036272-55-4 | [Synonyms]
((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate)
Decanoic acid, 2-hexyl-, 1,1'-[[(4-hydroxybutyl)imino]di-6,1-hexanediyl] ester
Decanoic acid, 2-hexyl-, 1,1'-[[(4-hydroxybutyl)imino]di-6,1-hexanediyl] ester ISO 9001：2015 REACH | [Molecular Formula]
C48H95NO5 | [MDL Number]
MFCD33402175 | [MOL File]
2036272-55-4.mol | [Molecular Weight]
766.27 |
| Chemical Properties | Back Directory | [Boiling point ]
760.6±55.0 °C(Predicted) | [density ]
0.919±0.06 g/cm3(Predicted) | [solubility ]
Soluble in Ethanol, DMSO, DMF | [pka]
15.11±0.10(Predicted) | [InChIKey]
QGWBEETXHOVFQS-UHFFFAOYSA-N | [SMILES]
N(CCCCCCOC(=O)C(CCCCCC)CCCCCCCC)(CCCCCCOC(=O)C(CCCCCC)CCCCCCCC)CCCCO |
| Hazard Information | Back Directory | [Description]
ALC-0315 ([(4-hydroxybutyl)azanediyl]di(hexane-6,1-diyl) bis(2-hexyldecanoate),2036272-55-4) is a synthetic lipid. A colorless oily material, it has attracted attention as a component of the SARS-CoV-2 vaccine, BNT162b2, from BioNTech and Pfizer. Specifically, it is one of four components that form lipid nanoparticles (LNPs), which encapsulate and protect the otherwise fragile mRNA that is the active ingredient in these drugs. These nanoparticles promote the uptake of therapeutically effective nucleic acids such as oligonucleotides or mRNA both in vitro and in vivo.
| [Uses]
ALC-0315(2036272-55-4) is one of the components of the BNT162b2 vaccine (0.43 mg per dose). Its chemical properties as a tertiary amine mean that its cation can form an ionic bond to the messenger RNA which carries the genetic information for the SARS-CoV-2 spike protein formation in the human body. Importantly, once the lipid nanoparticle which encapsulates the mRNA has been absorbed into antigen-presenting cells (a process called receptor-mediated endocytosis) the more acidic environment within the endosome fully protonates the ALC-0315 as a result the nanoparticle releases its payload of mRNA.
| [Application]
ALC-0315(2036272-55-4) is a cationic lipid and is critical to the self-assembly process of the particle itself, the ability of the particle to be taken up into cells and the escape of the RNA from the endosome.
ALC-0315 is the functional cationic lipid component of the drug product. When incorporated in lipid nanoparticles, it helps regulate the endosomal release of the RNA. During drug product manufacturing, introduction of an aqueous RNA solution to an ethanolic lipid mixture containing ALC-0315 at a specific pH leads to an electrostatic interaction between the negatively charged RNA backbone and the positively charged cationic lipid. This electrostatic interaction leads to encapsulation of RNA drug substance resulting with particle formation. Once the lipid nanoparticle is taken up by the cell, the low pH of the endosome renders the LNP fusogenic and allows the release of the RNA into the cytosol.
| [Biological Functions]
Main ingredient in the lipid-nanoparticle that delivers the mRNA into the cell.
Cationic (positively charged) lipid that during the manufacturing process, promotes the nanoparticle to assemble into a virus size particle with the negatively charged mRNA in the middle, and facilitates mRNA release from the nanoparticle once inside the cell. | [Biological Activity]
ALC-0315(2036272-55-4) is an ionizable amino lipid that has been used in combination with other lipids in the formation of lipid nanoparticles. Administration of severe acute respiratory coronavirus 2 (SARS-CoV-2) mRNA in ALC-0315-containing lipid nanoparticles induces the production of IgG that binds to the SARS-CoV-2 receptor-binding domain (RBD) in rhesus macaques, with a boost in antigen-specific IgG geometric mean titers (GMT) seven and 14 days after a second dose. Formulations containing ALC-0315 have been used in the development of lipid nanoparticles for the delivery of mRNA-based vaccines.
| [Side effects]
The most common adverse reaction to SARS-CoV-2 mRNA vaccine containing ALC-0315 (generated by Pfizer-BioNTech ) was anaphylaxis, with some patients experiencing systemic allergic reactions. The allergens of the LNP-based COVID-19 vaccine may be related to LNP (and/or vesicle) aggregates, and whether these aggregates can trigger allergic reactions remains to be evaluated. | [Synthesis]
The preparation of ALC-0315 was first described in a patent application to lipid nanoparticles by Acuitas Therapeutics in 2017.? The final step is a reductive amination reaction in which 4-aminobutanol is condensed with a lipid aldehyde, using sodium triacetoxyborohydride as the reducing agent to convert the intermediate imines to the amine of the product.
 | [References]
1. Vogel, A.B., Kanevsky, I., Che, Y., et al. BNT162b vaccines protect rhesus macaques from SARS-CoV-2. Nature 592(7853), 283-289 (2021). |
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