[R207910 (TMC207): a new antibiotic for the treatment of tuberculosis].
A new class of antibacterials, diarylquinolines, was identified. The lead compound, R207910 (TMC207), was able to inhibit Mycobacterium tuberculosis in vitro, in mice and in patients. R207910 targets the mycobacterial ATP synthase. In vitro, it displayed potent activities against both drug-sensitive and multidrug-resistant strains of M. tuberculosis. It was also strongly active against dormant bacilli in the Wayne's dormancy culture system, hypoxia and nitric oxide models. In the murine model, when used alone, it was as active as the triple combination of rifampicin+isoniazid+pyrazinamide. When added to the previous combination or substituted for isoniazid or rifampicin, the treatment including the combinations containing R207910 led to culture conversion after 2 months of therapy. When added to the combination used to treat MDR-TB or substituted for moxifloxacin or ethionamide, the combinations containing R207910 led to culture conversion after 2 months of therapy. In MDR-TB infected patients, R207910 combined with second line drugs was able to convert more sputum cultures (47.6%) than the placebo combined to second line drugs regimen (8.7%).
Lounis
N
N
Département de recherche antimicrobienne, Tibotec BVBA, Johnson & Johnson, 30, Turnhoutseweg, 2340 Beerse, Belgique. nlounis@its.jnj.com
Guillemont
J
J
Veziris
N
N
Koul
A
A
Jarlier
V
V
Andries
K
K
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001372:Aza Compounds / Q000627:therapeutic use; D064687:Diarylquinolines; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005000:Ethionamide / Q000627:therapeutic use; D024841:Fluoroquinolones; D006801:Humans; D051379:Mice; D000077266:Moxifloxacin; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D010919:Placebos; D011804:Quinolines / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy*
D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D001372:Aza Compounds; D064687:Diarylquinolines; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D010919:Placebos; D011804:Quinolines; C493870:bedaquiline; D005000:Ethionamide; D000077266:Moxifloxacin