A multi-targeted ligand-drug conjugate with endocytosis-mediated function

Abstract

The present invention discloses a multi-targeting ligand-drug conjugate with cell endocytosis mediating function, the drug conjugate includes a drug molecule and a linker coupled with the drug molecule, the drug conjugate The conjoined body includes at least two ligands that can specifically bind to cell surface receptors, at least one of the ligands has a first ligand that mediates endocytosis, and at least one of the ligands is combined with the first ligand. The ligands can be selectively coupled with the drug molecule or the linker to form a drug conjugate. The beneficial effect of the present invention lies in that: the combination of targeting and endocytic structures realizes the use of any ligand-targeted polypeptide as a guiding part, thereby broadening the targeting range of such drugs. Using multi-targeting ligands to enhance the affinity and targeting of drug conjugates to diseased cells can carry highly efficient toxin drugs such as MMAE, enhance drug efficacy and broaden the therapeutic window to avoid drug side effects.

Description

technical field [0001] The invention relates to a drug conjugate, in particular to a multi-targeting ligand-drug conjugate with a cell endocytosis mediating function, and belongs to the field of biomedical chemistry. Background technique [0002] Usually, the pathological and physiological characteristics of diseased cells are significantly different from those of normal cells, one of which is the specific or overexpressed substances (such as: antigens, chemical signals, receptors, etc.) on the surface of diseased cells. No expression or low expression. Antibody-drug conjugates (ADCs) and polypeptide-drug conjugates (PDCs) treat diseases based on this principle. Although some drugs have been marketed or entered clinical research, due to the principle of drug design, ADC and PDC drugs have great limitations in clinical application. [0003] ADC is currently mainly used in the field of tumor therapy. The targeting antibody used has a very high affinity for tumor cell surfac...

AI Technical Summary

Problems solved by technology

Therefore, when they are coupled with conventional chemotherapeutic drugs (such as doxorubicin, paclitaxel), the curative effect is low, and after coupling with high-efficiency drug molecules (such as MMAE, DM1, etc.), which are commonly used in ADCs, the toxicity is high, and the effective dose for tumor treatment will lead to animal poisoning death

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