The polypharmacology strategy of multi-targeting drugs acting on different biological pathways is capturing the researchers' attention, particularly in cancer. The simultaneous inhibition of two or more targets by drug combination or by a single 'hybrid molecule' can provide improved therapeutic efficacy when compared to the one-target inhibitors. In this regard, because of their multiple anticancer effects, histone deacetylase inhibitors have become a privileged tool for the development of hybrid drugs. The clinical trials of two multi-acting chimeras, HDAC/EGFR/HER2 and HDAC/PI3K inhibitors, encouraged the design of novel hybrids, such as compounds 22a (LSD1/HDAC) and 16a (CDK4/JAK1/HDAC), which showed superior anticancer effects than single-targeting agents or their combination both in cellular and mouse models.

中文翻译：

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组蛋白脱乙酰基酶作为表观遗传支柱，可用于开发癌症中的杂化抑制剂。

作用于不同生物途径的多靶点药物的多药理学策略正在吸引研究人员的注意力，尤其是在癌症领域。与单靶标抑制剂相比，通过药物组合或单个“杂合​​分子”同时抑制两个或多个靶标可提供更高的治疗功效。在这方面，由于其多种抗癌作用，组蛋白脱乙酰基酶抑制剂已成为开发杂交药物的优先工具。两种多作用嵌合体HDAC / EGFR / HER2和HDAC / PI3K抑制剂的临床试验鼓励了新型杂合体的设计，例如化合物22a（LSD1 / HDAC）和16a（CDK4 / JAK1 / HDAC），其表现出了优越的性能。在细胞和小鼠模型中的抗癌作用要比单一目标药物或其组合高。