Fast standardized therapeutic-efficacy assay for drug discovery against tuberculosis.
Murine models of Mycobacterium tuberculosis infection are essential tools in drug discovery. Here we describe a fast standardized 9-day acute assay intended to measure the efficacy of drugs against M. tuberculosis growing in the lungs of immunocompetent mice. This assay is highly reproducible, allows good throughput, and was validated for drug lead optimization using isoniazid, rifampin, ethambutol, pyrazinamide, linezolid, and moxifloxacin.
GlaxoSmithKline, Infectious Diseases Centre of Excellence in Drug Discovery, Diseases of the Developing World, Madrid, Spain.
Joaquín
J
Rullas
Juan Ignacio
JI
García
Manuela
M
Beltrán
Pere-Joan
PJ
Cardona
Neus
N
Cáceres
José Francisco
JF
García-Bustos
Iñigo
I
Angulo-Barturen
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology; D004195:Disease Models, Animal; D055808:Drug Discovery; D004977:Ethambutol / Q000494:pharmacology; D024841:Fluoroquinolones; D007121:Immunocompetence; D019570:Inhalation Exposure; D007538:Isoniazid / Q000494:pharmacology; D000069349:Linezolid; D051379:Mice; D008810:Mice, Inbred C57BL; D000077266:Moxifloxacin; D023303:Oxazolidinones / Q000494:pharmacology; D011718:Pyrazinamide / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D015203:Reproducibility of Results; D012293:Rifampin / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology
D000081:Acetamides; D000995:Antitubercular Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D023303:Oxazolidinones; D011804:Quinolines; D011718:Pyrazinamide; D004977:Ethambutol; D000069349:Linezolid; D000077266:Moxifloxacin; D007538:Isoniazid; D012293:Rifampin