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.

中文翻译：

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专门针对Mtb细胞壁和TMM转运蛋白：MmpL3抑制剂的开发。

结核病（TB）仍然是对整个人类健康的严重威胁。特别地，结核分枝杆菌（Mtb）的耐药性已成为临床医学中的巨大挑战，迫切需要开发具有新颖结构和机制的有效抑制剂。分支杆菌膜蛋白大分子3（MmpL3）属于抗性，结节和分裂（RND）超家族，主要负责将分支酸转移到细胞膜外以形成细胞壁，并且在铁的获取中起着至关重要的作用，这对铁的存活至关重要。山地车 作为近年来潜在的Mtb靶标，其抑制剂研究引起了广泛关注。相继报道了通过实验筛选的一系列抑制剂（如SQ109，AU1235，BM212等），特别是SQ109已进入临床阶段。