Activates an alternative bioactivation pathway of the tuberculosis antibiotic pro-drug ethionamide, reversing resistance.
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.
Science (New York, N.Y.), 355(6330), 1206-1211 (2017-03-18)
Antibiotic resistance is one of the biggest threats to human health globally. Alarmingly, multidrug-resistant and extensively drug-resistant
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