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.
Rights & PermissionsPrintExport