Peptidylarginine deaminase 4 (PAD4) is a crucial post-translational modifying enzyme catalyzing the conversion of arginine into citrulline residues, and mediating the formation of neutrophil extracellular traps (NETs). PAD4 plays a vital role in the occurrence and development of cardiovascular diseases, autoimmune diseases, and various tumors. Therefore, PAD4 is considered as a promising drug target for disease diagnosis and treatment. More and more efforts are devoted to developing highly efficient and selective PAD4 inhibitors via high-throughput screening, structure-based drug design and structure-activity relationship study. This article outlined the physiological and pathological functions of PAD4, and corresponding representative small molecule inhibitors reported in recent years.

肽精氨酸脱氨酶 4 (PAD4) 是一种重要的翻译后修饰酶，可催化精氨酸转化为瓜氨酸残基，并介导中性粒细胞胞外陷阱 (NETs) 的形成。PAD4在心血管疾病、自身免疫性疾病和各种肿瘤的发生发展中起着至关重要的作用。因此，PAD4被认为是一种很有前途的疾病诊断和治疗药物靶点。越来越多的努力致力于通过高通量筛选、基于结构的药物设计和构效关系研究来开发高效和选择性的 PAD4 抑制剂。本文概述了PAD4的生理和病理功能，以及近年来报道的相应具有代表性的小分子抑制剂。