Tuberculosis Drug Development: History and Evolution of the Mechanism-Based Paradigm

Cold Spring Harb Perspect Med. 2015 Apr 15;5(8):a021147. doi: 10.1101/cshperspect.a021147.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / pharmacology*
  • Diarylquinolines / administration & dosage
  • Diarylquinolines / pharmacology
  • Drug Design*
  • Drug Resistance, Bacterial
  • Drug Therapy, Combination
  • Ethambutol / administration & dosage
  • Ethambutol / pharmacology
  • Evolution, Chemical
  • Female
  • Humans
  • Isoniazid / administration & dosage
  • Isoniazid / pharmacology
  • Male
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / isolation & purification
  • Pyrazinamide / administration & dosage
  • Pyrazinamide / pharmacology
  • Rifampin / administration & dosage
  • Rifampin / pharmacology
  • Tuberculosis / drug therapy*
  • Tuberculosis, Multidrug-Resistant / drug therapy

Substances

  • Antitubercular Agents
  • Diarylquinolines
  • Pyrazinamide
  • bedaquiline
  • Ethambutol
  • Isoniazid
  • Rifampin