专利名称: Mertk Degraders and Uses Thereof
专利号: WO2020010210A1
公开日期: 2020年1月9日
发明者: Ji Nan 等

摘要 

Mertk是一种关键的受体酪氨酸激酶，其过度表达与多种肿瘤的发生和发展密切相关。专利WO2020010210A1描述了一类能够选择性降解Mertk的化合物，并探讨了其在癌症免疫治疗中的潜在应用。这些化合物通过靶向Mertk并利用细胞的泛素-蛋白酶体系统，实现对目标蛋白的高效降解，为精准医学提供了新的治疗策略。

Abstract
Mertk is a key receptor tyrosine kinase closely associated with tumorigenesis and progression in various cancers. Patent WO2020010210A1 describes compounds that selectively degrade Mertk and explores their potential applications in cancer immunotherapy. By targeting Mertk and utilizing the ubiquitin-proteasome system, these compounds achieve efficient degradation of the target protein, offering new therapeutic strategies in precision medicine.

作用机制与设计 

Mertk降解剂由三部分组成：靶向Mertk的配体、连接基团以及E3连接酶配体。它们通过将Mertk与E3连接酶桥接，触发目标蛋白的泛素化并降解。

Mechanism and Design
Mertk degraders are composed of three parts: a ligand targeting Mertk, a linker, and an E3 ligase ligand. They bridge Mertk and the E3 ligase, triggering ubiquitination and degradation of the target protein.

这种机制为治疗那些Mertk过度表达的肿瘤提供了一种创新方法。
This mechanism offers an innovative approach to treat tumors with overexpressed Mertk.

应用与前景 

Mertk降解剂在癌症治疗中展现了广阔的前景，特别是在免疫抑制性肿瘤微环境中。

Applications and Prospects
Mertk degraders show great promise in cancer therapy, especially in immunosuppressive tumor microenvironments.

未来研究方向包括：
Future research directions include:

• 开发针对不同E3连接酶的新型配体；
• 优化化合物的选择性与组织特异性；
• 探索其在其他疾病中的潜在应用（如炎症性疾病）。
• Developing novel ligands for diverse E3 ligases;
• Optimizing selectivity and tissue specificity of the compounds;
• Exploring potential applications in other diseases, such as inflammatory disorders.

总结 

Mertk降解剂代表了一种新兴的靶向治疗策略，能够通过降解特定蛋白来显著改善治疗效果。专利WO2020010210A1为其设计、合成及应用提供了宝贵的理论依据。

Conclusion
Mertk degraders represent an emerging targeted therapeutic strategy that can significantly improve treatment outcomes by degrading specific proteins. Patent WO2020010210A1 provides valuable insights into their design, synthesis, and applications.

Key Compounds and CAS Numbers / 相关化合物及其CAS号

Below are several related compounds and their CAS numbers mentioned in the context of Mertk degraders:
以下是与Mertk降解剂相关的几种化合物及其CAS号：

- Pomalidomide (CRBN E3 ligase ligand): CAS 19171-19-8

- Thalidomide (basic E3 ligase ligand): CAS 50-35-1

- Lenalidomide: CAS 191732-72-6

- Polyethylene glycol (PEG, commonly used linker): CAS 25322-68-3

- 1,4-Butanediol (fragment for chain extension): CAS 110-63-4

- dBET1 (PROTAC strategy validation compound): CAS 1799711-21-9

Conclusion 

Mertk degraders represent a novel approach in targeted therapy, offering potential in cancer treatment and other diseases. This document provides CAS numbers for related compounds as references.

总结
Mertk降解剂代表了一种新型的靶向治疗策略，为癌症治疗及其他疾病提供了潜在的应用。本文列举的相关化合物CAS号可供参考。