■含溴结构域蛋白4(BRD4),一个重要的表观遗传读者,与许多疾病的发生发展密切相关,包括各种癌症,炎症,和传染病。靶向BRD4抑制或蛋白质消除与小分子代表一个有前途的治疗策略,特别是癌症治疗。
■总结了获得专利的BRD4降解剂的最新进展。挑战,机遇,并讨论了开发新的有效和选择性BRD4降解剂的未来方向。使用SciFinder和Cortellis药物发现情报数据库搜索了BRD4降解剂的专利。
■BRD4降解剂表现出优于BRD4抑制剂的功效和选择性,鉴于其独特的蛋白质降解而不是蛋白质抑制机制。令人兴奋的是,RNK05047现在处于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,特别是癌症。用小分子BRD4降解物靶向BRD4提供了一种有希望的方法,其具有克服治疗各种BRD4相关疾病的治疗抗性的潜力。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.