Targeting ligand-drug conjugate having cell endocytosis mediating function

Abstract

The present invention discloses a targeting ligand-drug conjugate having a cell endocytosis mediating function. The targeting ligand-drug conjugate comprises a drug molecule and a linker coupled to the drug molecule, and is characterized by further comprising a molecule having a mediating effect and a ligand specifically bound to a cell surface receptor, wherein the ligand is a polypeptide or small molecule ligand, and the molecule can be coupled to the ligand, can be coupled to the drug molecule or linker to form the drug conjugate, or is respectively and separately coupled to one of the drug molecule and the linker to form the drug conjugate. According to the present invention, with the combination of the targeting and the endocytosis (transmembrane) structure, the any ligand targeting polypeptide can be adopted as the leader so as to broaden the targeting range of the drug; and with the conjugate, the stability of the drug during the in vivo circulation is ensured, and the drug toxicity is reduced.

Description

technical field [0001] The invention relates to a drug conjugate, in particular to a 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 surface anti...

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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