Pretomanid-d4 (PA-824-d4) is the deuterium labeled Pretomanid. Pretomanid (PA-824) is an antibiotic used for the research of multi-drug-resistant tuberculosis affecting the lungs. Pretomanid exhibits a sub-micromolar MIC against M. tuberculosis (MTB). The MIC values of PA-824 against a panel of MTB pan-sensitive and Rifampin mono-resistant clinical isolates range from 0.015 to 0.25 µg/mL[1][2].
体外研究 (In Vitro)
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs[1].
Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
363.28
Formula
C14H8D4F3N3O5
CAS 号
1346617-34-2
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
[2]. Stover CK, et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature. 2000 Jun 22;405(6789):962-6.
[3]. Lenaerts AJ, et al. Preclinical testing of the nitroimidazopyran PA-824 for activity against Mycobacterium tuberculosis in a series of in vitro and in vivo models. Antimicrob Agents Chemother. 2005 Jun;49(6):2294-301.
[4]. Manjunatha UH, et al. Mycobacterium leprae is naturally resistant to PA-824. Antimicrob Agents Chemother. 2006 Oct;50(10):3350-4.
Pretomanid (PA-824) is an antibiotic used for the research of multi-drug-resistant tuberculosis affecting the lungs. Pretomanid exhibits a sub-micromolar MIC against M. tuberculosis (MTB). The MIC values of PA-824 against a panel of MTB pan-sensitive and Rifampin mono-resistant clinical isolates range from 0.015 to 0.25 µg/mL[1].
IC50 & Target
Tuberculosis.
体外研究 (In Vitro)
Pretomanid (PA-824) exhibited a sub-micromolar minimal inhibitory concentration (MIC) against MTB, Although Pretomanid (PA-824) was not the most potent NAP against cultured MTB clinical isolates, it was the most active in infected mice when orally administered at 25 mg/kg. This indicated that Pretomanid (PA-824) might possess more desirable pharmacokinetic properties than the other more potent NAP compounds that we tested. Further studies in mice at 25, 50 and 100 mg kg-1 Pretomanid (PA-824) daily for 10 days resulted in reductions of mycobacterial burden in both spleen and lung tissues that were comparable to that of INH at 25 mg kg -1 [1]. Pretomanid (PA-824) showed significant activity at 2, 10, and 50 microg/ml, similar to that of metronidazole, in a dose-dependent manner. Pretomanid (PA-824) at 100 mg/kg in cyclodextrin/lecithin was as active as moxifloxacin at 100 mg/kg and isoniazid at 25 mg/kg and was slightly more active than rifampin at 20 mg/kg. Long-term treatment with Pretomanid (PA-824) at 100 mg/kg in cyclodextrin/lecithin reduced the bacterial load below 500 CFU in the lungs and spleen [2]. Pretomanid (PA-824) has no effect on the viability of M. leprae in all three models, consistent with the lack of the nitroimidazo-oxazine-specific nitroreductase, encoded by Rv3547 in the M. leprae genome, which is essential for activation of this molecule [3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
359.26
Formula
C14H12F3N3O5
CAS 号
187235-37-6
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Stover CK, et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature. 2000 Jun 22;405(6789):962-6.
[2]. Lenaerts AJ, et al. Preclinical testing of the nitroimidazopyran PA-824 for activity against Mycobacterium tuberculosis in a series of in vitro and in vivo models. Antimicrob Agents Chemother. 2005 Jun;49(6):2294-301.
[3]. Manjunatha UH, et al. Mycobacterium leprae is naturally resistant to PA-824. Antimicrob Agents Chemother. 2006 Oct;50(10):3350-4.