Tuberculosis (TB) remains a serious threat to whole human health. In particular, the drug resistance of Mycobacterium tuberculosis (Mtb) has become a huge challenge in clinical medicine, and it is extremely urgent to develop effective inhibitors with novel structures and mechanisms. Belonging to the Resistance, Nodulation and Division (RND) superfamily, Mycobacterial membrane proteins Large 3 (MmpL3) is mainly responsible for transporting mycolic acid outside cell membrane to form cell wall, and plays critical roles in iron acquisition which is vital to the survival of Mtb. As a potential Mtb target in recent years, its inhibitor research has attracted wide attention. A series of inhibitors (such as SQ109, AU1235, BM212, etc.) through experimental screening have been reported in succession, especially SQ109 has entered the clinical stage. In this paper, the structural biology information of target MmpL3 was summarized, and the structure-activity relationship (SAR) of inhibitors reported in recent years and their inhibitory mechanism both were reviewed, aiming to provide help for the rational design of MmpL3 inhibitors in the future.

结核病（TB）仍然对整个人类健康构成严重威胁。特别是结核分枝杆菌（Mtb）的耐药性已成为临床医学的巨大挑战，开发具有新颖结构和机制的有效抑制剂迫在眉睫。分枝杆菌膜蛋白大 3 (MmpL3) 属于抵抗、结瘤和分裂 (RND) 超家族，主要负责将分枝菌酸转运到细胞膜外形成细胞壁，并在铁的获取中发挥关键作用，这对细菌的生存至关重要。山地车。作为结核分枝杆菌的潜在靶点，其抑制剂研究近年来受到广泛关注。一系列通过实验筛选的抑制剂（如SQ109、AU1235、BM212等）相继被报道，特别是SQ109已进入临床阶段。本文综述了靶点MmpL3的结构生物学信息，并对近年来报道的抑制剂的构效关系（SAR）及其抑制机制进行了综述，旨在为MmpL3抑制剂的合理设计提供帮助。未来。