以铁调素为靶点的新药研发

The Development of New Drug Targeting Hepcidin

铁是人体必不可少的微量元素之一,机体会对自身铁含量进行调节维持体内铁平衡。体内铁平衡遭到破坏使体内的铁缺失或过载便会引发多种疾病。铁调素作为一种小分子多肽类激素,对铁代谢调节起负调控作用,也已成为治疗铁代谢相关疾病一个新靶点。笔者综述铁调素的结构,其对铁代谢的调节作用与调控机制,机体对铁调素的调控机制,铁调素失衡导致的相关疾病等;同时,综述了以铁调素为靶点的新药研究类型与进展。由于对铁调素研究的不断深入,逐渐发展出针对铁调素信号转导途径中特定分子的特异性靶向治疗方法,通过铁调素的激活剂或拮抗剂,促进或抑制铁调素的表达,从而从分子水平上改善或治疗铁代谢紊乱的相关疾病。铁调素本身、以小化合物与siRNA为代表的铁调素激活剂、以肝素衍生物为代表的铁调素拮抗剂等都有望成为纠正铁稳态紊乱相关疾病的新药。

Iron is one of the essential trace elements in the human body, the body adjusts its own iron content to maintain iron bal- ance. Iron imbalance, either iron deficiency or over load can cause variety of diseases. As a small molecule peptide hormones, hepci- din negatively regulates iron metabolism. It has become a new therapeutic target for iron disorder diseases. The structure of hepcidin, its regulation mechanism of iron metabolism, the regulatory mechanism of hepcidin in the body, and related diseases caused by hepci- din imbalance were reviewed. This article also reviewed the types and advances of new drugs targeting hepcidin. Due to the continuous research on hepcidin, a specific targeted therapy for specific molecules in the hepcidin signaling pathway has been gradually developed. Through hepcidin activator or antagonist, it can promote or inhibit the expression of hepcidin, thereby improving or treating disorders related to iron metabolism disorders at the molecular level. Hepcidin itself, hepcidin activator represented by small chemical com- pounds and siRNA, and hepcidin antagonist represented by beparin derivatives are hopeful new drugs to correct disorders related to iron homeostasis.