Pretomanid

Manufactured by Merck Group

Pretomanid is a novel antimycobacterial compound developed by the Tuberculosis Alliance. It is a nitroimidazooxazine derivative that inhibits mycolic acid biosynthesis in Mycobacterium tuberculosis. Pretomanid has been shown to have potent activity against drug-resistant strains of tuberculosis.

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3 protocols using pretomanid

Evaluation of Promising Anti-TB Drugs

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Isoniazid (INH), Rifampicin (RIF), Ethionamide (ETH), and Pretomanid (PMD) were purchased from Sigma; Delamanid (DMD) was procured from MedKoo Biosciences. All antibiotics were dissolved in DMSO with exception of INH, which when used for treatment of mice, was dissolved in H₂O.

Kreutzfeldt K.M., Jansen R.S., Hartman T.E., Gouzy A., Wang R., Krieger I.V., Zimmerman M.D., Gengenbacher M., Sarathy J.P., Xie M., Dartois V., Sacchettini J.C., Rhee K.Y., Schnappinger D, & Ehrt S. (2022). CinA mediates multidrug tolerance in Mycobacterium tuberculosis. Nature Communications, 13, 2203.

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Synthesis and Characterization of TA-C Derivatives

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The synthesis of TA-C has been described previously (15 (link)). Synthesis of TA-C-Red is described in SI Appendix, Supplementary Information. TA-C-Met and TA-C-Acid were purchased from BioDuro. PAS, pretomanid, isoniazid, rifampicin, and kanamycin sulfate were purchased from Sigma-Aldrich. All drugs and chemicals were dissolved in 100% dimethyl sulfoxide (DMSO) at 10 mM except kanamycin, which was dissolved to 50 mg/mL in deionized water and sterilized using 0.2-μm Minisart high-flow syringe filters (Sartorius).

Aragaw W.W., Lee B.M., Yang X., Zimmerman M.D., Gengenbacher M., Dartois V., Chui W.K., Jackson C.J, & Dick T. (2021). Potency boost of a Mycobacterium tuberculosis dihydrofolate reductase inhibitor by multienzyme F420H2-dependent reduction. Proceedings of the National Academy of Sciences of the United States of America, 118(25), e2025172118.

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Tuberculosis Drug Efficacy Evaluation

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Pretomanid, streptomycin sulfate, ethambutol dihydrochloride, ethionamide, isoniazid, linezolid and standards (glucose-6-phosphate, ribose-5-phosphate, fructose-6-phosphate and methylglyoxal) were obtained from Sigma. Kanamycin sulfate, ampicillin sodium salt and rifampicin were obtained from Gibco, Melford and Duchefa Biochemie respectively.

Baptista R., Fazakerley D.M., Beckmann M., Baillie L, & Mur L.A. (2018). Untargeted metabolomics reveals a new mode of action of pretomanid (PA-824). Scientific Reports, 8, 5084.

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