What is ALC-0315?

What is ALC-0315?

Published by BroadPharm on February 10, 2023

Lipid nanoparticles (LNP) have played an important role in the creation and approval of mRNA vaccines. One of the more notable lipids found in Pfizer’s COVID-19 vaccine BNT162b2 is ALC- 0315.

ALC-0315 is an amino lipid with a tertiary amine linked with a branched tail through ester bonds. The tertiary amine allows the lipid to form a zwitterionic lipid. ALC-0315 is a colorless oily compound with a molecular weight of 766.3 and a CAS number of 2036272-55-4 IUPAC name is [(4-Hydroxybutyl)azanediyl]di(hexane-6,1-diyl) bis(2-hexyldecanoate).

ALC-0315 can be synthesized through the route as shown in Figure 1.

alc-0315 image

Figure 1. Shows the synthesis route of ALC-0315.

ALC-0315 is an ideal drug carrier due to its fast clearance rate, tolerability, immunogenicity, and protein expression. While ALC-0315 is soluble in organic solvents, it forms a membrane when suspended in polar solvents. The tertiary amine forms an ionic bond to mRNA allowing for ideal encapsulation of the mRNA payload. ALC-0315 remains neutral at physiological pH and takes on a positive charge in an acidic environment. This property to stay neutral at physiological pH allows the lipid to have fewer interactions with the anionic membranes of blood cells. ALC- 0315’s ability to take on a positive charge plays an important role after cellular uptake. When ALC-0315 interacts with the acidic endosome, the tertiary amine becomes protonated and forms cone-shaped ion pairs that drive the transition from a bilayer to an inverted hexagon phase. This phase promotes endosomal escape and the release of the mRNA into the cytosol. Once the mRNA is released, ALC-0315 is metabolized through two sequential ester hydrolysis reactions first yielding the monoester metabolite followed by the doubly de-esterified metabolite. The product of both hydrolysis reactions is 6-hexyldecanoic acid. The remaining aliphatic head group is eliminated via biliary and renal clearance.

With the recent advances in nanoparticle drug delivery technology, the scientific community is on the edge of many new therapeutics being created. To further empower drug delivery, BroadPharm offers a broad selection of ionizable lipids, cationic lipids, PEG lipids, and Phospholipids. BroadPharm also offers custom lipid syntheses to further satisfy your research need.

Please don’t hesitate to contact sales@broadpharm.com or call (858) 677-6760 for timely support.