SMARt-420 (Small Molecule Aborting Resistance) activates an alternative bioactivation pathway of the tuberculosis antibiotic pro-drug ethionamide. Ethionamide bioactivation is normally catalyzed by monooxygenase EthA, but mutations in the enzyme have allowed many strains to become resistant. SMARt-420 activates a previously unknown pathway, reversing ethionamide-acquired resistance and clearing ethionamide-resistant infection in mice in addition to increasing the sensitivity of bacteria to ethionamide.
