一种以亚甲基蓝类似物作为蛋白降解子的2-(4-羟苯基)苯并噻吩类化合物及其应用
By introducing a methylene blue analogue as a singlet oxygen trigger tag onto the raloxifene analogue backbone, combined with light or ultrasound stimulation, highly efficient and selective degradation of ERα protein was achieved. This solves the problems of large molecular weight, poor tissue specificity, and poor drug-likeness in existing technologies, and provides a new targeted protein degradation strategy.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- GUIZHOU UNIV
- Filing Date
- 2024-06-16
- Publication Date
- 2026-07-17
AI Technical Summary
Existing targeted protein degradation technologies, such as PROTAC, have problems in breast cancer treatment, including large molecular weight, poor tissue specificity, poor drug-likeness, and significant toxic side effects, making it difficult to effectively overcome drug resistance and improve selectivity.
Using methylene blue analogues as singlet oxygen triggering group tags, combined with raloxifene analogue skeletons, singlet oxygen is generated through light or ultrasound stimulation to achieve high spatiotemporal resolution degradation of ERα protein. A benzothiophene compound containing a singlet oxygen triggering group tag was designed and synthesized.
This study achieved highly efficient and selective degradation of ERα protein, reduced the molecular weight of the compound, improved drug-likeness and cell membrane permeability, simplified the synthesis process, and provided a new targeted degradation strategy.
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Figure CN119751438B_ABST