Hypoxia-responsive protein degradation targeting chimera compound as well as preparation method and application thereof

By designing an oxygen-responsive PROTAC prodrug based on azobenzene and using it in combination with photodynamic therapy, the existing PROTACs are solved, and the systemic toxicity and poor treatment effect after systemic administration is achieved, a more efficient and safer anti-tumor effect is achieved, and a real-time monitoring mechanism for drug release is provided.

CN119638779APending Publication Date: 2025-03-18TSINGHUA UNIVERSITY
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Patent Information

Application Number
CN202411694828.1
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-11-25
Publication Date
2025-03-18

AI Technical Summary

Technical Problem

Existing PROTACs cause systemic toxicity after systemic administration and are poorly effective in tumor treatment, especially due to the limited activation efficiency of hypoxia-activated prodrugs and the lack of a reporting mechanism for drug activation.

Method used

An hypoxic responsive PROTAC prodrug based on azobenzene was designed and used in combination with photodynamic therapy to improve antitumor effects. By utilizing the reducing properties of azo bonds in an hypoxic environment, active PROTAC drugs and photosensitizers are released, so that the degradation of BET protein and induced apoptosis of tumor cells can be achieved.

Benefits of technology

This method not only improves the safety of PROTAC, but also significantly enhances the synergistic treatment effect on tumors, can effectively inhibit the growth of breast cancer cells, and provides a mechanism for real-time monitoring of drug release.

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Abstract

The invention provides a hypoxia-responsive protein degradation targeting chimera compound as well as a preparation method and application thereof. The structure of the compound is as shown in a formula (VII), and more specifically as shown in a formula (I). The compound disclosed by the invention takes an azo bond as a hypoxia response unit, can respond to a hypoxia tumor microenvironment and activate a protein degradation function of the hypoxia tumor microenvironment, and meanwhile, recovers a fluorescence signal of a photosensitizer so as to monitor drug release in real time. Under the irradiation of near-infrared light, the photosensitizer generates active oxygen to induce tumor cell apoptosis, so that photodynamic therapy and PROTAC combined therapy are realized. The compound provided by the invention can solve the problems of systemic toxicity after administration of an existing PROTACs drug system and poor effect in tumor treatment, and meanwhile, can monitor drug release in real time, so that the compound has good practical application value. # imgabs0 #
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