CONJUGATES OF MONOMETHYL AURISTATIN E WITH ASIALOGLYCOPROTEIN RECEPTOR LIGANDS FOR TARGETED TRANSPORT INTO TUMOR CELLS OF LIVER Russian patent published in 2023 - IPC A61K47/55 A61K47/62 A61P35/00 

FIELD: medicinal chemistry.

SUBSTANCE: invention relates to low-molecular conjugates of the antitumor monomethyl auristatin E, in which the active substance is connected to an N-acetylgalactosamine residue with a cleavable cathepsin B dipeptide linker valine-citrulline or a non-cleavable linker based on hex-5-ynic acid. A method of producing the conjugate and its use for the preparation of a pharmaceutical composition for the treatment of hepatocellular carcinoma are also proposed.

EFFECT: conjugates are characterized by greater efficiency in relation to the ASGPR-expressing cell line (HepG2), and also have cytotoxicity at the level of medicinal products of similar action used in clinical practice, and are stable under conditions that mimic physiological ones (pH 5.0 and 7.4), but are subject to hydrolysis under the action of a mixture of Pronase enzymes.

12 cl, 4 dwg, 1 tbl, 11 ex