The discovery of histone deacetylase (HDAC) inhibitors is a hot topic in the medicinal chemistry community regarding cancer research. This is related primarily to two factors: success in the clinic, e. g., the four FDA‐approved HDAC inhibitors, and strong versatility to combine their pharmacophoric features to design new hybrid compounds with multitarget profiles. Thus, the selection of adequate pharmacophores to combine, i. e., combining targets that can result in a synergistic effect, is desirable, as it increases the probability of discovering a new useful therapeutic strategy. In this work, we highlight the design of multitarget HDAC/PI3K inhibitors. Although this approach is still in its early stages, many significant works have described the design and pharmacological evaluation of this new promising class of multitarget inhibitors, where compound CUDC‐907, which is already in clinical trials, stands out. Therefore, the question emerges of whether there still space for the design and evaluation of new multitarget HDAC/PI3K inhibitors. When considering the selectivity profile of the described multitarget compounds, the answer appears to be in the affirmative, especially since the first examples of compounds with a certain selectivity profile only recently appeared in 2020.

中文翻译：

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组蛋白脱乙酰酶 (HDAC) 和磷脂酰肌醇 3 激酶 (PI3K) 的多靶点抑制：当前和未来前景

组蛋白去乙酰化酶 (HDAC) 抑制剂的发现是药物化学界关于癌症研究的热门话题。这主要与两个因素有关：临床上的成功，例如。例如，四种 FDA 批准的 HDAC 抑制剂，以及结合它们的药效特征以设计具有多靶点特征的新型混合化合物的强大多功能性。因此，选择足够的药效团进行组合，即。例如，结合可以产生协同效应的目标是可取的，因为它增加了发现新的有用治疗策略的可能性。在这项工作中，我们重点介绍了多靶点 HDAC/PI3K 抑制剂的设计。尽管这种方法仍处于早期阶段，但许多重要的工作已经描述了这种新型多靶点抑制剂的设计和药理学评估，其中已经在临床试验中的化合物 CUDC-907 脱颖而出。因此，新的多靶点HDAC/PI3K抑制剂的设计和评估是否还有空间的问题就出现了。考虑到所描述的多目标化合物的选择性特征时，答案似乎是肯定的，特别是因为具有特定选择性特征的化合物的第一个例子最近才出现在 2020 年。