选择性组蛋白去乙酰化酶3抑制剂的治疗前景研究进展

Therapeutic Potential of Selective Histone Deacetylase 3 Inhibitiors

组蛋白去乙酰化酶3(histone deacetylase 3, HDAC3)是特异性催化组蛋白尾部的赖氨酸残基去乙酰化的I类HDAC家族成员,与多种疾病的发生发展密切相关。近年来,随着多个泛HDAC药物在临床广泛使用后显示较大毒副作用,亚型选择性抑制剂及其疾病表型成为当前研究热点。目前由于HDAC3能够调控多种疾病转录因子的表达,使高选择性HDAC3抑制剂在治疗肿瘤、炎症、糖尿病、心血管疾病以及神经退行性疾病中展现出巨大潜力。因此,本文综述选择性抑制HDAC3对多种疾病治疗机制的研究进展,为以HDAC3为靶点的药物开发提供研究思路。

Histone deacetylase 3(HDAC3), as a member of class I HDAC, can specifically catalyze the deacetylation of lysine residues in histone tails. It is closely related to the occurrence and development of a variety of diseases. With multiple pan-HDAC drugs showing toxic and side effects in clinics, the study of highly selective inhibitors against subtypes of HDAC and their disease phenotypes has become a research hotspot. In recent times, because HDAC3 can regulate the expression of transcription factors of many diseases, selective HDAC3 inhibitors showed potential effective treatment of tumor, inflammation, diabetes,cardiovascular, neurodegenerative diseases, etc. Therefore, this review summarizes the research progress of selective HDAC3 inhibitors in the treatment of various diseases, and provides a new approach for the development of drugs targeting HDAC3.