Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.

含溴结构域蛋白 4 (BRD4) 正在成为一种治疗靶点，与癌症中小分子药物的其他靶点协同作用。因此，发现潜在的新的 BRD4 双靶点抑制剂可能是癌症治疗的一种有前途的策略。在这篇综述中，我们重点介绍了一系列设计 BRD4 治疗性双靶点抑制剂的策略，这些抑制剂专注于这种蛋白质的协同功能。利用合成杀伤力、蛋白质-蛋白质相互作用、功能互补性和阻断耐药机制的药物组合最终可以克服开发 BRD4 抑制剂作为未来癌症药物所固有的障碍。