Guo Jing-Si, Liu Kai-Li, Qin Yu-Xi, Hou Lin, Jian Ling-Yan, Yang Yue-Hui, Li Xin-Yang
Department of Pharmacy, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Shenyang 110004, PR China.
School of Pharmacy, China Medical University, No. 77 Puhe, Shenyang 110122, PR China.
Biomed Pharmacother. 2023 Nov;167:115440. doi: 10.1016/j.biopha.2023.115440. Epub 2023 Sep 8.
The discovery of new therapeutic strategies for diseases is essential for drug research. Deoxyhypusine synthase (DHPS) is a critical enzyme that modifies the conversion of the eukaryotic translation initiation factor 5A (eIF5A) precursor into physiologically active eIF5A (eIF5A-Hyp). Recent studies have revealed that the hypusine modifying of DHPS on eIF5A has an essential regulatory role in human diseases. The hypusination-induced DHPS/eIF5A pathway has been shown to play an essential role in various cancers, and it could regulate immune-related diseases, glucose metabolism-related diseases, neurological-related diseases, and aging. In addition, DHPS has a more defined substrate and a well-defined structure within the active pocket than eIF5A. More and more researchers are focusing on the prospect of advanced development of DHPS inhibitors. This review summarizes the regulatory mechanisms of the hypusination-induced DHPS/eIF5A pathway in a variety of diseases in addition to the inhibitors related to this pathway; it highlights and analyzes the structural features and mechanisms of action of DHPS inhibitors and expands the prospects of future drug development using DHPS as an anticancer target.
发现针对疾病的新治疗策略对药物研究至关重要。脱氧hypusine合酶（DHPS）是一种关键酶，它催化真核生物翻译起始因子5A（eIF5A）前体转化为具有生理活性的eIF5A（eIF5A-Hyp）。最近的研究表明，DHPS对eIF5A的hypusine修饰在人类疾病中具有重要的调节作用。已证明由hypusination诱导的DHPS/eIF5A途径在各种癌症中起重要作用，并且它可以调节免疫相关疾病、葡萄糖代谢相关疾病、神经相关疾病和衰老。此外，与eIF5A相比，DHPS在活性口袋内具有更明确的底物和更明确的结构。越来越多的研究人员关注DHPS抑制剂的进一步开发前景。本综述总结了由hypusination诱导的DHPS/eIF5A途径在多种疾病中的调节机制以及与此途径相关的抑制剂；它突出并分析了DHPS抑制剂的结构特征和作用机制，并拓展了以DHPS作为抗癌靶点未来药物开发的前景。
