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EC Number Application Commentary Reference
Display the word mapDisplay the reaction diagram Show all sequences 1.1.98.2medicine PA-824 is a compound for the treatment of tuberculosis (undergoing human trials). PA-824 is a prodrug of the nitroimidazole class, requiring bioreductive activation of an aromatic nitro group to exert an antitubercular effect. Resistance to PA-824 (a nitroimidazo-oxazine) and CGI-17341 (a nitroimidazo-oxazole) is most commonly mediated by loss of a specific glucose-6-phosphate dehydrogenase or its deazaflavin cofactor F420, which together provide electrons for the reductive activation of this class of molecules. Although glucose-6-phosphate dehydrogenase and F420 are necessary for sensitivity to these compounds, they are not sufficient and require additional accessory proteins that directly interact with the nitroimidazole. The sensitivity of Mtb to PA-824 and related compounds is mediated by a protein that is highly specific for subtle structural variations in these bicyclic nitroimidazoles 700931
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