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Current Protein & Peptide Science

Editor-in-Chief

ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Review Article

Specifically Targeting Mtb Cell-Wall and TMM Transporter: The Development of MmpL3 Inhibitors

Author(s): Qing Luo, Huaichuan Duan, Hailian Yan, Xinyu Liu, Lianxin Peng, Yichen Hu, Wei Liu, Li Liang, Hubing Shi*, Gang Zhao* and Jianping Hu *

Volume 22, Issue 4, 2021

Published on: 21 April, 2021

Page: [290 - 303] Pages: 14

DOI: 10.2174/1389203722666210421105733

Price: $65

Abstract

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.

Keywords: Anti-tubercular agents, M. tuberculosis, MmpL3, inhibitor, structure-activity relationship, TMM transporter.

Graphical Abstract


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