| Literature DB >> 29269214 |
Rostislav A Petrov1, Svetlana Yu Maklakova1, Yan A Ivanenkov2, Stanislav A Petrov1, Olga V Sergeeva3, Emil Yu Yamansarov1, Irina V Saltykova1, Igor I Kireev4, Irina B Alieva4, Ekaterina V Deyneka5, Alina A Sofronova6, Anastasiia V Aladinskaia5, Alexandre V Trofimenko5, Renat S Yamidanov7, Sergey V Kovalev1, Victor E Kotelianski8, Timofey S Zatsepin3, Elena K Beloglazkina1, Alexander G Majouga9.
Abstract
Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug - paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC.Entities:
Keywords: ASGP-R; Cancer; Paclitaxel; Targeted drug delivery
Mesh：
Substances：
Year: 2017 PMID： 29269214 DOI： 10.1016/j.bmcl.2017.12.032
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823