期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/ijms231710014
关键词
histone deacetylase; HDAC8; HDAC8 inhibitor; fibrosis; cancer; polypharmacology
资金
- Regione Toscana, Bando Ricerca Salute 2018, grant named Precise-CLL
- Bando Ricerca Salute 2018, grant named HIDE-IPF
HDAC8, an important enzyme, plays a role in various diseases and selective HDAC8 inhibitors are being developed. Polypharmacological approaches have also been explored.
Histone deacetylases (HDACs) are epigenetic enzymes which participate in transcriptional repression and chromatin condensation mechanisms by removing the acetyl moiety from acetylated epsilon-amino group of histone lysines and other non-histone proteins. In recent years, HDAC8, a class I HDAC, has emerged as a promising target for different disorders, including X-linked intellectual disability, fibrotic diseases, cancer, and various neuropathological conditions. Selective HDAC8 targeting is required to limit side effects deriving from the treatment with pan-HDAC inhibitors (HDACis); thus, many endeavours have focused on the development of selective HDAC8is. In addition, polypharmacological approaches have been explored to achieve a synergistic action on multi-factorial diseases or to enhance the drug efficacy. In this frame, proteolysis-targeting chimeras (PROTACs) might be regarded as a dual-targeting approach for attaining HDAC8 proteasomal degradation. This review highlights the most relevant and recent advances relative to HDAC8 validation in various diseases, providing a snapshot of the current selective HDAC8is, with a focus on polyfunctional modulators.
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