Valente Sergio, Mai Antonello
Sapienza Università di Roma, Dipartimento di Chimica e Tecnologie del Farmaco , P.le A. Moro 5, 00185 Roma , Italy +39 064 991 3392 ; +39 064 969 3268 ;
Expert Opin Ther Pat. 2014 Apr;24(4):401-15. doi: 10.1517/13543776.2014.877446. Epub 2014 Jan 8.
Histone deacetylases (HDACs) play an important role in mediating the expression of genes involved in cancer and non-cancer diseases. Overexpression of these enzymes has been shown in several types of cancer and some enzyme isoforms were described as responsible for neurological and inflammatory pathologies, hence the use of HDAC inhibitors represents a strategy for their treatment. Different chemical entities have been developed in the recent years and some of them entered clinical trials.
This review accounts for small-molecule inhibitors of HDAC reported in the patent literature covering the 2011 - 2013 period, and their potential use as therapeutics for cancer, neurological and inflammatory diseases.
The development of isoform-selective HDAC inhibitors to avoid side effects in cancer therapy, to fight specific types of cancer, or for their potential use in non-cancer diseases is ongoing but still needs many scientific efforts. Moreover, the strategy of using these agents in combination with other epigenetic target modulators is a recent interesting therapeutic approach that could give promising results.
组蛋白脱乙酰酶（HDACs）在介导参与癌症和非癌症疾病的基因表达中发挥着重要作用。这些酶的过表达已在多种类型的癌症中得到证实，并且一些酶亚型被认为与神经和炎症性疾病有关，因此使用HDAC抑制剂是治疗这些疾病的一种策略。近年来已开发出不同的化学实体，其中一些已进入临床试验阶段。
本综述阐述了2011年至2013年专利文献中报道的HDAC小分子抑制剂，以及它们作为癌症、神经和炎症性疾病治疗药物的潜在用途。
开发亚型选择性HDAC抑制剂以避免癌症治疗中的副作用、对抗特定类型的癌症或用于非癌症疾病的潜在用途的研究正在进行中，但仍需要大量科学努力。此外，将这些药物与其他表观遗传靶点调节剂联合使用的策略是一种近期有趣的治疗方法，可能会产生有前景的结果。
