Structural Modifications and Prospects of Histone Deacetylase (HDAC) Inhibitors in Cancer

Title:Structural Modifications and Prospects of Histone Deacetylase (HDAC) Inhibitors in Cancer

Volume: 32

Author(s): Yu Chen, Jiahong Su, Sha Li, Feier Chen, Yan Zhang, Xingyue Wang, Yinping Zhang, Xiang Wang, Zijun Yuan, Siqi Ren, Xinyu He, Yueshui Zhao, Xu Wu, Mingxing Li, Fukuan Du, Shuai Deng, Jing Shen and Zhangang xiao*

Affiliation:

• Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China
• Cell Therapy & Cell Drugs of Luzhou Key Laboratory, South Sichuan Institute of Translational Medicine, Luzhou, 646000, Sichuan, China

Keywords: HDACis, cancer, dual target inhibitors, HDAC8, HDAC10, PROTAC, clinical research.

Abstract: Histone deacetylases (HDACs) play a crucial role in the regulation of cancer progression and have emerged as key targets for antitumor therapy. Histone Deacetylase Inhibitors (HDACis) effectively suppress tumor cell proliferation, induce apoptosis, and cause cell cycle arrest, demonstrating broad-spectrum antitumor activity. This article primarily focuses on enhancing the selectivity of HDACis through structural modification using natural compounds. It provides detailed insights into the structure modification of histone deacetylase 8 (HDAC8) and histone deacetylase 10 (HDAC10), as well as dual-- target inhibitors and their pharmacological effects. Furthermore, conventional HDAC inhibitors are susceptible to off-target effects and the development of drug resistance. Our research focuses on augmenting the targeting specificity of HDAC inhibitors through their combination with proteolysis targeting chimera (PROTAC). Lastly, the latest advancements in clinical research on HDAC inhibitors were summarized, revealing that these inhibitors possess limitations in their clinical applications due to intrinsic or acquired resistance. Consequently, this article primarily focuses on summarizing the current status and prospects of structural modifications for HDAC inhibitors, with the aim of inspiring researchers to develop novel HDAC inhibitors exhibiting enhanced activity for improved application in clinical research.

Cite this article as:

Chen Yu, Su Jiahong, Li Sha, Chen Feier, Zhang Yan, Wang Xingyue, Zhang Yinping, Wang Xiang, Yuan Zijun, Ren Siqi, He Xinyu, Zhao Yueshui, Wu Xu, Li Mingxing, Du Fukuan, Deng Shuai, Shen Jing and xiao Zhangang*, Structural Modifications and Prospects of Histone Deacetylase (HDAC) Inhibitors in Cancer, Current Medicinal Chemistry 2025; 32 () . https://dx.doi.org/10.2174/0109298673332285241104091609