N-acetyl-D-galactosamine (GalNAc)

N-acetyl-D-galactosamine (GalNAc) is an amino sugar derivative of galactose that serves as a vital component in biological glycosylation processes and cell-surface signaling. In the context of modern biotechnology, GalNAc is primarily utilized as a highly specific targeting ligand for the Asialoglycoprotein receptor (ASGPR), which is abundantly expressed on the sinusoidal membrane of hepatocytes (PubChem CID 35717; UniProt P07306). This molecular interaction allows for the precise delivery of therapeutic agents, particularly RNA interference (RNAi) therapeutics like siRNAs and antisense oligonucleotides, directly to the liver. By conjugating three GalNAc units to a drug molecule—forming a triantennary structure—the drug achieves nanomolar affinity for the receptor, ensuring efficient cellular uptake via receptor-mediated endocytosis (Nature Biotechnology, 2017). This platform has revolutionized the treatment of liver-associated metabolic and genetic diseases by enhancing potency and significantly reducing systemic side effects. Approved therapies using this mechanism include Inclisiran for hypercholesterolemia and Givosiran for acute hepatic porphyria, marking GalNAc as a cornerstone of hepatic-targeted drug development.

Other names

2-(Acetylamino)-2-deoxy-D-galactose2-Acetamido-2-deoxy-D-galactoseAcetylgalactosamineGalNAc ligand

GalNAc-conjugated drugs bind with high affinity and specificity to the Asialoglycoprotein receptor (ASGPR) expressed on the surface of hepatocytes, facilitating rapid receptor-mediated endocytosis and intracellular delivery of the therapeutic payload.