Heterobifunctional compound for targeted degradation of BRD4 based on HSP70, preparation and application

By designing HSP70-BRD4 heterobifunctional compounds, using HSP70 ligand to link chain linker to form compounds, the problems of large toxic side effects and low selectivity of existing BRD4 inhibitors are solved, and the BRD4 protein is efficiently degraded, providing new targeted therapy strategies.

CN119285649APending Publication Date: 2025-01-10CHINA PHARM UNIV
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Patent Information

Application Number
CN202411408283.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-10-10
Publication Date
2025-01-10

AI Technical Summary

Technical Problem

Existing BRD4 inhibitors have problems with large toxic side effects and low selectivity, and lack heterobifunctional small molecules that can target BRD4 and HSP70 at the same time.

Method used

A class of heterobifunctional compounds based on HSP70 targeted degradation of BRD4 can be designed to form compounds through HSP70 ligand and BRD4 inhibitor (+)-JQ-1 linker, and target tumor cells using HSP70 ligand, thereby improving the The role of BRD4 inhibitors in tumor cells.

Benefits of technology

It significantly improved the role of BRD4 inhibitors in tumor cells, reduced toxic side effects, and improved selectivity. In particular, the BRD4 protein degradation rate of compound AB-13 in leukemia MV-4-11 cells reached 90%, providing new Targeted protein degradation methods and drug discovery strategies.

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Abstract

The invention provides a hetero-bifunctional compound for targeted degradation of BRD4 based on HSP70, and preparation and application thereof, and belongs to the technical field of pharmaceutical synthesis chemical industry. An HSP70 inhibitor is selected as a ligand part A combined with HSP70, a BRD4 inhibitor is selected as a ligand part B combined with BRD4, and the ligand A of HSP70 and the ligand B of BRD4 are connected through a connecting chain Linker to obtain a series of bifunctional degradation agents capable of degrading BRD4 to different degrees, and the obtained degradation agents have the characteristics of high selectivity and strong activity, and can be used for degrading BRD4 in different degrees. The defects of poor selectivity, strong toxic and side effects and the like of a BRD4 inhibitor on tumor tissues can be overcome.
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Citation Information

Patent Citations

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Cited By

  • Heterobifunctional compound for targeted degradation of BRD4 based on HSP70, preparation, and use

    WO2026076912A1