Taxane medicinal precursor

Abstract

The invention discloses a taxane medicinal precursor, which is a conjugate formed by bonding a hydroxyl group at C-2' or C-7 position of a taxane compound and water-soluble targeting peptide through a conjugation bridge, wherein the conjugation bridge contains at least one of an ester bond, a carbonic ester bond, a urea bond and a disulfide bond. Compared with the taxane compound, the medicinal precursor has the advantages that the medicinal precursor has extremely high water solubility capable of reaching 2mg / ml, so that the problem that the taxane compound can only be dissolved by using an unsafe substance such as an organic solvent and tween 80 in the prior art is solved; due to the adoption of a covalent coupling mode, the taxane medicinal precursor is ensured to have high stability when being stored in vitro, and the taxane compound can be rapidly released to achieve medicinal effects after the taxane medicinal precursor enters cells; the taxane compound can be carried to a specific tumor cell through the targeting peptide to reduce killing ability to normal cells; a decomposed product of the targeting peptide in the cells is amino acid, so that high biocompatibility is ensured.

Description

technical field

[0001] The invention relates to a taxane drug prodrug, in particular to a taxane drug prodrug. Background technique

[0002] Taxane drugs mainly include paclitaxel and docetaxel, which are currently one of the most effective clinical antitumor drugs. Paclitaxel is a tetracyclic diterpenoid isolated from the bark of Pacific yew with the molecular formula C 47 h 51 o 14 N, the molecular weight is 853.9, insoluble in water. Approved by the US FDA in 1992, its mechanism of action is to bind to cellular tubulin and promote tubulin polymerization to resist depolymerization and block mitosis, thereby inhibiting tumor growth and inducing tumor cell apoptosis. Clinical studies have confirmed that paclitaxel has a significant effect in the treatment of various solid tumors, including breast cancer, advanced ovarian cancer, lung cancer, brain and neck tumors, and acute leukemia. Docetaxel is semi-synthesized from the non-cytotoxic precursor compound 10-deacylated b...

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