What is "pretomanid"

Pretomanid (PA-824) is an experimental anti- tuberculosis drug. Pretomanid is a bicyclic nitroimidazole-like molecule with a very complex mechanism of action. It is active against both replicating and hypoxic, non-replicating Mycobacterium tuberculosis. Microarray analysis of the mode of action of pretomanid showed a puzzling mixed effect both on genes responsive to cell wall inhibition (like isoniazid) and respiratory poisoning (like cyanide). The aerobic killing mechanism of this drug appears to involve inhibition of cell wall mycolic acid biosynthesis through an as yet unknown molecular mechanism.The respiratory poisoning through nitric oxide release seemed to be a crucial element of anaerobic activity by pretomanid. The effect of pretomanid on the respiratory complex under hypoxic non-replicating conditions was also manifested in a rapid drop in intracellular ATP levels, again similar to that observed by cyanide treatment. Pretomanid recently was shown to be safe, well tolerated, and efficacious at doses of 100–200 mg daily in a dose-ranging study among drug-sensitive, sputum smear–positive, adult pulmonary TB patients

PA-824 was developed at Pathogenesis Corporation and later transferred to the TB Alliance, where it is currently undergoing Phase III clinical trials.