d-lin-mc3-dma

D-Lin-MC3-DMA is a synthetic ionizable cationic lipid that serves as a benchmark delivery component in lipid nanoparticle (LNP) formulations for nucleic acid therapeutics. It is characterized by a pH-sensitive dimethylamino headgroup that remains neutral at physiological pH (7.4), minimizing toxicity and extending circulation time, but becomes protonated in the acidic environment of the endosome (pKa ~6.44). This protonation facilitates endosomal escape by promoting fusion with the endosomal membrane, thereby releasing the encapsulated cargo—such as siRNA, mRNA, or circular RNA—into the cytoplasm. D-Lin-MC3-DMA was the first ionizable lipid to be utilized in an FDA-approved LNP-based drug, patisiran (Onpattro), developed by Alnylam Pharmaceuticals for the treatment of hereditary transthyretin-mediated amyloidosis.

Other names

dilinoleylmethyl-4-dimethylaminobutyratedilinoleylmethyl4-dimethylaminobutyratedilinoleylmethyl 4-dimethylaminobutyrate(6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate