FIELD: chemistry; medicine.
SUBSTANCE: group of inventions relates to biotechnology and medicine, in particular to stability-modulated antibody-drug conjugates (ADC), stability-modulating linker components used to make these ADC, method for treating a cancer using said conjugates and method of making the conjugates. Antibody-drug conjugate has structure (I):
(I) or structure (II), and the linker component has structure (III), as defined in the claims. Antibody-drug conjugate is obtained by transglutaminase mediated conjugation. Method of treating a cancer in a subject in need comprises administering an effective amount of ADC to the subject. Linkers (III) used in conjugates ADC are able to up- and down-modulate the extracellular and/or intracellular stability of antibody-drug conjugates, so that more or less relative amount of the payload of ADCs is released at the desired site.
EFFECT: inventions permit the fine-tuning of ADC stability in vivo and permit the optimization of the therapeutic index of ADCs.
19 cl, 3 dwg, 9 tbl, 72 ex
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|---|---|---|---|
| LIGAND CONJUGATE WITH CYTOTOXIC DRUG PREPARATION, METHOD AND APPLICATION THEREOF | 2016 |
|
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| CYTOTOXIC PEPTIDES AND ANTIBODY-DRUG CONJUGATES THEREOF | 2012 |
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| ANTIBODY AND MEDICINAL AGENT CONJUGATE AND USE THEREOF FOR TREATING CANCER | 2015 |
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| CONJUGATE OF ANTI-IGF-1R ANTIBODY WITH DRUG AND USE THEREOF FOR TREATING CANCER | 2015 |
|
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| ANTIBODY AND DRUG CONJUGATES (ADC) AND ANTIBODY AND PRODRUG CONJUGATES (APDC) CONTAINING ENZYMATICALLY CLEAVABLE GROUPS | 2016 |
|
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| NEW CONJUGATES BINDING COMPOUND - ACTIVE COMPOUND (ADC) AND USE THEREOF | 2012 |
|
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| PROTEOLYSIS MODULATORS AND RELATED USES | 2019 |
|
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| 5-(7H-PYRROLO[2,3-d]PYRIMIDINE-4-YL)-5-AZASPIRO[2.5]OCTANE-8-CARBOXYLIC ACID DERIVATIVES AS NEW JAK-KINASE INHIBITORS | 2018 |
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RU2761626C2 |
