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TBA-354 

Cat. No. M28070
TBA-354  Structure
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Biological Activity

TBA-354 is a potent anti-tuberculosis compound. TBA-354 maintains activity against Mycobacterium tuberculosis H37Rv isogenic monoresistant strains and clinical drug-sensitive and drug-resistant isolates. TBA-354 is 5 to 10 times more potent than PA-824, but selected mutants are cross-resistant to PA-824 and delamanid.

Chemical Information
Molecular Weight 436.34
Formula C19H15F3N4O5
CAS Number 1257426-19-9
Form Solid
Solubility (25°C) DMSO 100 mg/mL (ultrasonic)
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Sphamandla Ntshangase, et al. Xenobiotica. The downfall of TBA-354 - a possible explanation for its neurotoxicity via mass spectrometric imaging

[2] Rashmi Tandon, et al. Mini Rev Med Chem. Tackling Drug-Resistant Tuberculosis: Current Trends and Approaches

[3] Deepak Kumar, et al. Future Med Chem. The anti-tuberculosis agents under development and the challenges ahead

[4] Rokeya Tasneen, et al. Antimicrob Agents Chemother. Contribution of the nitroimidazoles PA-824 and TBA-354 to the activity of novel regimens in murine models of tuberculosis

[5] A M Upton, et al. Antimicrob Agents Chemother. In vitro and in vivo activities of the nitroimidazole TBA-354 against Mycobacterium tuberculosis

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