BRD4降解剂的最新专利综述
An updated patent review of BRD4 degraders
DOI 原文链接
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影响因子:4.6
分区:医学2区 / 药物化学2区 药学2区
发表日期:2024 Oct
作者:
Zonghui Ma, Cun Zhang, Andrew A Bolinger, Jia Zhou
DOI:
10.1080/13543776.2024.2400166
摘要
含溴域蛋白4（BRD4）是一种重要的表观遗传阅读器，密切相关多种疾病的发病机制和发展，包括多种癌症、炎症和感染性疾病。通过小分子靶向BRD4抑制或蛋白质降解，已成为一种有潜力的治疗策略，尤其在癌症治疗中。本文总结了近期已获专利的BRD4降解剂的研究进展，探讨了开发新型高效且选择性强的BRD4降解剂的挑战、机遇和未来方向。利用SciFinder和Cortellis药物发现情报数据库检索了BRD4降解剂的专利。BRD4降解剂通过其独特的蛋白质降解机制，显示出优于传统BRD4抑制剂的疗效和选择性。令人振奋的是，RNK05047已进入I/II期临床试验，表明选择性BRD4蛋白降解可能成为一种可行的治疗策略，尤其适用于癌症。靶向BRD4的小分子降解剂为解决耐药问题提供了新途径，有望在多种BRD4相关疾病中展现出临床应用潜力。
Abstract
Bromodomain-containing protein 4 (BRD4), an important epigenetic reader, is closely associated with the pathogenesis and development of many diseases, including various cancers, inflammation, and infectious diseases. Targeting BRD4 inhibition or protein elimination with small molecules represents a promising therapeutic strategy, particularly for cancer therapy.The recent advances of patented BRD4 degraders were summarized. The challenges, opportunities, and future directions for developing novel potent and selective BRD4 degraders are also discussed. The patents of BRD4 degraders were searched using the SciFinder and Cortellis Drug Discovery Intelligence database.BRD4 degraders exhibit superior efficacy and selectivity to BRD4 inhibitors, given their unique mechanism of protein degradation instead of protein inhibition. Excitingly, RNK05047 is now in phase I/II clinical trials, indicating that selective BRD4 protein degradation may offer a viable therapeutic strategy, particularly for cancer. Targeting BRD4 with small-molecule degraders provides a promising approach with the potential to overcome therapeutic resistance for treating various BRD4-associated diseases.