BRD4降级器的更新专利评论
An updated patent review of BRD4 degraders
影响因子:4.60000
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
摘要
重要的表观遗传学读取器含溴化群蛋白4（BRD4）与许多疾病的发病机理和发育密切相关，包括各种癌症，炎症和感染性疾病。用小分子靶向BRD4抑制作用或蛋白质消除是一种有希望的治疗策略，特别是对于癌症治疗。总结了专利的BRD4脱脂剂的最新进展。还讨论了开发新颖和选择性的BRD4退化器的挑战，机会和未来的方向。鉴于其独特的蛋白质降解机制而不是蛋白质抑制作用，因此使用Scifinder和Cortellis药物发现智能数据库搜索了BRD4降解器的专利。BRD4降解器对BRD4抑制剂具有较高的疗效和选择性。令人兴奋的是，RNK05047现在正在I/II期临床试验中，表明选择性BRD4蛋白降解可能提供可行的治疗策略，尤其是针对癌症。用小分子降解器靶向BRD4提供了一种有希望的方法，具有克服治疗各种BRD4相关疾病的治疗耐药性的潜力。
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.