New Anti-Tuberculosis Drugs in Clinical Development: An Overview

Jerome      Guillemont; Frederic      Lieby-Muller; Nacer      Lounis; Wendy      Balemans; Anil      Koul; Koen      Andries

doi:10.2174/157340709788451975

Abstract

Tuberculosis (TB) remains one of the most deadly infectious diseases in the world, killing about 2 million people per year, and mostly affecting the worlds poorest population. The length of current regimens for treatment of TB is long (6-9 months) with a high pill burden. Furthermore, one third of the world population is infected, though asymptomatically, with latent TB and is at risk of developing active TB disease during their lifetime. The current TB epidemic is fuelled by co-infection with HIV, the rise of multidrug-resistant strains, and the ability of the bacterium to become dormant in the lungs and to be reactivated in immunocompromised people. Despite medical advances over the last decades, including the genomic and proteomic revolution, TB still is a highly neglected disease. However, the search for new TB drugs is gaining momentum. Several efforts are underway to develop new drugs, within the academia, the pharmaceutical industry and as public private partnerships. This review will provide a chemical, biological and pharmacological overview of the six drug candidates currently in clinical development. Moxifloxacin (fluoroquinolone), TMC207 (diarylquinoline), PA-824 and OPC-67683 (nitroimidazoles), LL3858 (pyrrole) and SQ109 (ethambutol analogue) will be presented.

Keywords: Infectious disease, Mycobacterium tuberculosis, Moxifloxacin, TMC207, PA824, OPC67683, LL3858, SQ109