Аннотация:Liver cancer takes fifth place in the rating of most common types among men and theeighth among women worldwide. The most common type of liver cancer is hepatocellularcarcinoma (HCC) - more than 75% of liver cancer is HCC. 1 Now, to treat this type of canceroncologists are using cytotoxic drugs which also affect healthy tissues.The main goal of the work was to study targeted delivery to the liver. So the focuswas to find the most promising target cells and drug molecules. In this work, theasialoglycoprotein receptor was chosen as the delivery site, which is the best option fortargeted delivery of drugs to the liver due to its location on the surface of hepatocytes. Astargeting molecules native ligands of ASGPR were used. We chose modified triterpenic andbile acids as medical molecules. In their unmodified state they show anticancer and anti-inflammatory properties. Studies were held to obtain ligands’ dissociation constants todetermine which of them have the potential to be used in therapy. Spectroscopy of surfaceplasmon resonance was used to study the parameters of interaction of ASGPR with variousligands.Multivalent ligands were demonstrating a cooperative effect. Dissociation constantdecreases with increasing amount of N-acetylgalactosamine (GalNAc) residues: K D = 19,6 ±9,8 nM(mono-), K D = 1,3 ± 1,1 nM(bi-), K D = 0,7 ± 0,2 nM(three-). The length of the linkerbetween the skeleton of the molecule and the residue of GalNAc had an impact on theobtained dissociation constant. This is presumably due to an increase in the mobility ofGalNAc: K D = 0,8 ± 0,1 nM for long linker and K D = 19,5 ± 9,8 nM for the long one. The effectof the presence of hydroxyl groups in the skeleton of bile acid on binding to the receptor alsohad an impact on the obtained dissociation constant. We assume that this is due to achange in the hydrophobicity of the ligand. Steric factors on nonspecific binding of triterpenicacids to the hydrophobic site of ASGPR influenced obtained data. This can mean that someform of non-specific binding is taking place when ASGPR reacts with ligands.Few of studied ligands with the obtained values of the dissociation constant less than1 nM can be considered as leading compounds for the further development of a platform fortargeted drug delivery to hepatocytes.This study was supported in part by the Russian Science Foundation grant 20-63-46029, State Topic АААА-А21-121011290089-4 and MSU Program of Development.