title: Tuberculosis Drug Development: History and Evolution of the Mechanism-Based Paradigm.
abstract: Modern tuberculosis (TB) chemotherapy is widely viewed as a crowning triumph of anti-infectives research. However, only one new TB drug has entered clinical practice in the past 40 years while drug resistance threatens to further destabilize the pandemic. Here, we review a brief history of TB drug development, focusing on the evolution of mechanism(s)-of-action studies and key conceptual barriers to rational, mechanism-based drugs.
authors: Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College, New York, New York 10021 Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10021.
authors: Sumit
authors: S
authors: Chakraborty
authors: Division of Infectious Diseases, Department of Medicine, Weill Cornell Medical College, New York, New York 10021 Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10021.
authors: Kyu Y
authors: KY
authors: Rhee
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D064687:Diarylquinolines / Q000008:administration & dosage / Q000494:pharmacology; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage / Q000494:pharmacology; D019418:Evolution, Chemical; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D011718:Pyrazinamide / Q000008:administration & dosage / Q000494:pharmacology; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; D011718:Pyrazinamide; C493870:bedaquiline; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin