Abstract
Several groups working in the field of the development of new antituberculosis drugs have recently reported active compounds targeting mycobacterial enzyme DprE1. Along with its counterpart, DprE2, it catalyses a unique epimerization reaction resulting in the synthesis of decaprenylphosphoryl arabinose, the single donor of arabinosyl residues for the build-up of arabinans, fundamental components of the mycobacterial cell wall. This review presents the historical background leading to the discovery of DprE1, focusing on the biochemical and structural characterization of this important emerging target and introducing the molecules acting on DprE1 including the development of the most successful series – the benzothiazinones, currently in late pre-clinical development, which turned to be suicide inhibitors of DprE1.
Keywords: Tuberculosis, drug target, DprE1, structure, inhibitors, SAR, benzothiazinones.
Current Pharmaceutical Design
Title:DprE1 - from the Discovery to the Promising Tuberculosis Drug Target
Volume: 20 Issue: 27
Author(s): Katarina Mikusova, Vadim Makarov and Joao Neres
Affiliation:
Keywords: Tuberculosis, drug target, DprE1, structure, inhibitors, SAR, benzothiazinones.
Abstract: Several groups working in the field of the development of new antituberculosis drugs have recently reported active compounds targeting mycobacterial enzyme DprE1. Along with its counterpart, DprE2, it catalyses a unique epimerization reaction resulting in the synthesis of decaprenylphosphoryl arabinose, the single donor of arabinosyl residues for the build-up of arabinans, fundamental components of the mycobacterial cell wall. This review presents the historical background leading to the discovery of DprE1, focusing on the biochemical and structural characterization of this important emerging target and introducing the molecules acting on DprE1 including the development of the most successful series – the benzothiazinones, currently in late pre-clinical development, which turned to be suicide inhibitors of DprE1.
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Cite this article as:
Mikusova Katarina, Makarov Vadim and Neres Joao, DprE1 - from the Discovery to the Promising Tuberculosis Drug Target, Current Pharmaceutical Design 2014; 20 (27) . https://dx.doi.org/10.2174/138161282027140630122724
DOI https://dx.doi.org/10.2174/138161282027140630122724 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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