FIELD: chemistry.
SUBSTANCE: invention relates to a method for producing an antibody-drug conjugate represented by the following formula: (maleimide-N-yl)-(CH2)n3-C(=O)-L2-LP-NH-(CH2)n1-La-(CH2)n2-C(=O)-(NH-DX) with an anti-HER2 antibody or a reactive derivative thereof, and conjugating the linker-drug group with the antibody in a manner to form a thioether bond at the disulphide bonds site represented in the hinge portion of the antibody, where n1 is an integer from 0 to 6, n2 is an integer from 0 to 5, n3 is an integer from 2 to 8, L2 is -NH-(CH2CH2-O)n4 -CH2CH2-C(=O)- or a single bond, where n4 is an integer from 1 to 6, LP is a tetrapeptide residue -GGFG-, La is -O- or a single bond, and -(NH-DX) is a group represented by the following formula:
,
where the nitrogen atom of the amino group in position 1 is in the bonding position.
EFFECT: conjugate has excellent antitumor activity.
19 cl, 14 dwg, 49 ex
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Authors
Dates
2023-04-12—Published
2015-01-28—Filed