Literature DB >> 24325728

MmpL3 a potential new target for development of novel anti-tuberculosis drugs.

Geetha Vani Rayasam1.   

Abstract

INTRODUCTION: Tuberculosis (TB) is still a leading cause of mortality in the developing world and there is an unmet clinical need for new drugs with novel mechanism of action. Targeting the complex and unique cell wall of TB-causing pathogen Mycobacterium tuberculosis (Mtb) has been a mainstay of TB drug discovery. Though, the composition of the cell wall of Mtb is well understood, little is known about the assembly process of the cell wall such as the transport of mycolic acids across the cell wall. AREAS COVERED: Recent research demonstrating MmpL3 protein as a transmembrane transporter of mycolic acids is discussed. In addition, MmpL3 has also been implicated in heme transport. Research describing several diverse chemical inhibitors that inhibit MmpL3 is reviewed. EXPERT OPINION: Evidence so far suggests MmpL3 is a transporter of mycolic acids. It has emerged as a novel therapeutic target for Mtb that is essential and for which several small molecule inhibitors have been identified. Identifying the interacting partners, understanding the substrate specificity and the mechanism of transport by MmpL3 are some of the gaps in knowledge that need to be addressed.

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Year:  2013        PMID: 24325728     DOI: 10.1517/14728222.2014.859677

Source DB:  PubMed          Journal:  Expert Opin Ther Targets        ISSN: 1472-8222            Impact factor:   6.902


  9 in total

1.  Computational design of MmpL3 inhibitors for tuberculosis therapy.

Authors:  R Chaitra; Rohit Gandhi; N Jayanna; Sachin Satyanath; Parasuraman Pavadai; Manikanta Murahari
Journal:  Mol Divers       Date:  2022-04-28       Impact factor: 2.943

2.  Design, Synthesis, and Biological Evaluation of Pyrrole-2-carboxamide Derivatives as Mycobacterial Membrane Protein Large 3 Inhibitors for Treating Drug-Resistant Tuberculosis.

Authors:  Hongyi Zhao; Yongxin Gao; Wei Li; Li Sheng; Keli Cui; Bin Wang; Lei Fu; Meng Gao; Ziyun Lin; Xiaowen Zou; Mary Jackson; Haihong Huang; Yu Lu; Dongfeng Zhang
Journal:  J Med Chem       Date:  2022-08-01       Impact factor: 8.039

3.  Targeting the trehalose utilization pathways of Mycobacterium tuberculosis.

Authors:  Sandeep Thanna; Steven J Sucheck
Journal:  Medchemcomm       Date:  2015-10-16       Impact factor: 3.597

4.  The EXIT Strategy: an Approach for Identifying Bacterial Proteins Exported during Host Infection.

Authors:  E F Perkowski; K E Zulauf; D Weerakoon; J D Hayden; T R Ioerger; D Oreper; S M Gomez; J C Sacchettini; M Braunstein
Journal:  MBio       Date:  2017-04-25       Impact factor: 7.867

5.  Advancing the Therapeutic Potential of Indoleamides for Tuberculosis.

Authors:  Shichun Lun; Rokeya Tasneen; Tridib Chaira; Jozef Stec; Oluseye K Onajole; Tian J Yang; Christopher B Cooper; Khisi Mdluli; Paul J Converse; Eric L Nuermberger; V Samuel Raj; Alan Kozikowski; William R Bishai
Journal:  Antimicrob Agents Chemother       Date:  2019-06-24       Impact factor: 5.191

Review 6.  Advances in Key Drug Target Identification and New Drug Development for Tuberculosis.

Authors:  Jie Mi; Wenping Gong; Xueqiong Wu
Journal:  Biomed Res Int       Date:  2022-02-25       Impact factor: 3.411

Review 7.  Indole: A promising scaffold for the discovery and development of potential anti-tubercular agents.

Authors:  Nilesh Gajanan Bajad; Sudhir Kumar Singh; Sushil Kumar Singh; Tryambak Deo Singh; Meenakshi Singh
Journal:  Curr Res Pharmacol Drug Discov       Date:  2022-07-16

8.  Optimization and Lead Selection of Benzothiazole Amide Analogs Toward a Novel Antimycobacterial Agent.

Authors:  Mary A De Groote; Thale C Jarvis; Christina Wong; James Graham; Teresa Hoang; Casey L Young; Wendy Ribble; Joshua Day; Wei Li; Mary Jackson; Mercedes Gonzalez-Juarrero; Xicheng Sun; Urs A Ochsner
Journal:  Front Microbiol       Date:  2018-09-20       Impact factor: 5.640

9.  Cryo-EM structure and resistance landscape of M. tuberculosis MmpL3: An emergent therapeutic target.

Authors:  Oliver Adams; Justin C Deme; Joanne L Parker; Philip W Fowler; Susan M Lea; Simon Newstead
Journal:  Structure       Date:  2021-07-08       Impact factor: 5.006

  9 in total

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