Despite much research and undeniable advances, cancer treatment and prevention has remained a major challenge for scientists. Both genetic and epigenetic changes are involved in the growth and development of cancer complex and multifactorial disease. Among the possible treatment options, multidrug epigenetic therapy such as the use of dual epigenetic inhibitors, has been a popular option in recent years. Histone deacetylases (HDACs) as epigenetic eraser and bromodomain-containing protein 4 (BRD4) as epigenetic reader are epigenetic modifiers, which are rapidly being investigated. Using of a single molecule that simultaneously targets HDACs and BRD4 has been recently employed by medicinal chemists. Presently, there are no approved BRD4 inhibitor and dual BRD4/HDAC inhibitor in the drug market but evidence suggests their possible therapeutic potential in various diseases, such as cancer. In this review, the overall structure of the synthesized dual BRD4/HDAC small molecule inhibitors, lead compounds, and the biological and pharmacological properties of the most potent dual BRD4/HDAC inhibitor in each category are all collected in the hopes of assisting in the development of stronger and more selective dual BRD4/HDAC inhibitors in future studies.

尽管有很多研究和不可否认的进步，但癌症治疗和预防仍然是科学家面临的主要挑战。遗传和表观遗传变化都参与了癌症复杂和多因素疾病的生长和发展。在可能的治疗选择中，多药表观遗传疗法，例如使用双重表观遗传抑制剂，近年来一直是一种流行的选择。作为表观遗传擦除器的组蛋白去乙酰化酶 (HDAC) 和作为表观遗传阅读器的含溴结构域蛋白 4 (BRD4) 是表观遗传修饰剂，正在迅速被研究。使用同时靶向 HDAC 和 BRD4 的单个分子最近已被药物化学家采用。目前，药物市场上没有批准的 BRD4 抑制剂和双重 BRD4/HDAC 抑制剂，但有证据表明它们在各种疾病（如癌症）中可能具有治疗潜力。本综述收集了合成的双BRD4/HDAC小分子抑制剂的整体结构、先导化合物，以及各类别中最有效的双BRD4/HDAC抑制剂的生物学和药理特性，希望对开发有所帮助。在未来的研究中更强大和更具选择性的双重 BRD4/HDAC 抑制剂。