OTB-658
OTB-658 is a conformationally restricted oxazolidinone antibacterial candidate that exhibits bacteriostatic activity against Mycobacterium tuberculosis. OTB-658 enters macrophages and inhibits intracellular M. tuberculosis growth. OTB-658 exhibits dose-dependent antibacterial activity. OTB-658 is used in research related to tuberculosis and drug-resistant tuberculosis.
For research use only. We do not sell to patients.
- CAS No.: 2245791-50-6
- Formula: C17H20FN3O4S
- Molecular Weight:381.42
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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- References
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Help & FAQs
Biological Activity
Description
In Vitro
OTB-658 (0.0156-1.0 μg/mL; 7 days) inhibits the growth of M. tuberculosis H37Rv, 10 drug-sensitive clinical isolates, and 30 multidrug-resistant clinical isolates, with MICs of 0.080-0.115 μg/mL, 0.008-0.015 μg/mL, and <0.016-0.167 μg/mL for the three groups of strains, respectively, and no cross-resistance with INH/RIF is observed among the multidrug-resistant clinical isolates[1].
OTB-658 (7 days) exhibits an MBC >32 × MIC against M. tuberculosis H37Rv and clinical isolates, indicating bacteriostatic rather than bactericidal activity[1].
OTB-658 (14 days) produces time-dependent growth inhibition against M. tuberculosis H37Rv and clinical isolates, and does not produce a significant CFU bactericidal decrease even at higher tested concentrations[1].
OTB-658 (0.5-5 μg/mL; 72 h) reduces the bacterial burden from 5.42 log10 CFU/mL in the control group to 4.97, 4.65, and 4.53 log10 CFU/mL, respectively, in J774A.1 macrophages infected with M. tuberculosis H37Rv, indicating that OTB-658 enters macrophages and inhibits intracellular bacterial growth[1].
The spontaneous resistance mutation frequency of OTB-658 (3 weeks) against wild-type M. tuberculosis is 9.09 × 10-9-3.3 × 10-8[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
OTB-658 (25-100 mg/kg; p.o.; 5 times per week; 8 weeks) dose-dependently reduces lung and spleen bacterial burdens in BALB/c mice with chronic M. tuberculosis H37Rv infection; after 8 weeks, lung bacterial loads decrease by approximately 1.5, 2.5, and 3 log10 CFU/lung, respectively[1].
OTB-658 (50 mg/kg; oral gavage; 5 times per week; 8 weeks; in combination with BDQ 25 mg/kg and PMD 100 mg/kg) reduces lung and spleen bacterial burdens to 0.72 and 0.58 log10 CFU, respectively, in M. tuberculosis H37Rv-infected C3HeB/FeJ mice, representing reductions of more than 7.50 and 3.89 log10 CFU, respectively, compared with the untreated group; no culture-positive relapse in the lungs is observed after 12 weeks of follow-up following treatment discontinuation[2].
OTB-658 (50-100 mg/kg; oral gavage; 5 times per week; 8 weeks; in combination with TBI-166 20 mg/kg and BDQ 25 mg/kg) reduces lung and spleen bacterial burdens in C3HeB/FeJ mice infected with M. tuberculosis H37Rv; the 100 mg/kg group shows lung and spleen bacterial burdens of 0.53 log10 CFU, with a 40% lung relapse rate observed 12 weeks after treatment cessation, compared with 100% in the 50 mg/kg group[2].
OTB-658 (100 mg/kg; oral gavage; 5 times per week; 4 or 8 weeks; in combination with TBI-166 20 mg/kg and BDQ 25 mg/kg) achieves culture negativity in both lungs and spleens at 4 and 8 weeks in M. tuberculosis H37Rv-infected BALB/c mice; after 12 weeks of observation following drug withdrawal, the relapse rate in the lungs is 60% in the 4-week treatment group and decreases to 6.67% in the 8-week treatment group, with no relapse observed in the spleens of the 8-week group[2].
OTB-658 (100 mg/kg; oral gavage; 5 times per week; 4 or 8 weeks; alone or in combination with TBI-166 (HY-148564) at 20 mg/kg) exhibits potent pulmonary antibacterial activity as a monotherapy in BALB/c mice infected with M. tuberculosis H37Rv; the combination with TBI-166 does not further reduce the pulmonary bacterial burden in the OTB-658 group, suggesting that TBI-166 does not enhance the in vivo anti-tuberculosis activity of OTB-658[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c (female, 18-20 g, infected via aerosol with Mycobacterium tuberculosis H37Rv)[1]
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Dosage:25, 50, and 100 mg/kg
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Administration:five times per week; 3 weeks
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Result:Reduced lung CFU counts to 3.10 log10 CFU at 25 mg/kg, 2.09 log10 CFU at 50 mg/kg, and 1.58 log10 CFU at 100 mg/kg.
Achieved approximately 3 log10 CFU reduction in the 50 mg/kg group compared to the CMC group.
Showed no significant differences in body weight among groups, with weights of 20.61 g (25 mg/kg), 20.34 g (50 mg/kg), and 20.71 g (100 mg/kg).
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Animal Model:BALB/c (female, 18-20 g, infected via aerosol with Mycobacterium tuberculosis H37Rv)[1]
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Dosage:25, 50, and 100 mg/kg
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Administration:p.o.; five times per week; 8 weeks
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Result:Reduced lung bacterial load by approximately 1.5, 2.5, and 3 log10 CFU/lung at 25, 50, and 100 mg/kg, respectively, after 8 weeks of treatment compared with the Lzd and CMC groups.
Showed slightly reduced spleen CFU counts in the three OTB-658 groups after the first 4 weeks.
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Animal Model:C3HeB/FeJ (female, 6-8 weeks old, 18-20 g, aerosol-infected with M. tuberculosis H37Rv)[2]
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Dosage:50 mg/kg (BDQ + PMD backbone); 50 mg/kg or 100 mg/kg (TBI-166 + BDQ backbone)
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Administration:p.o.; five times per week (Monday to Friday); 8 weeks
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Result:Reduced bacterial burden by more than 7.50 log10 CFU in the lungs and 3.89 log10 CFU in the spleen compared to untreated controls in the BDQ + PMD + OTB-658(50) group.
Resulted in 0% relapse from lungs in the BDQ + PMD + OTB-658(50) group at 12 weeks post-treatment.
Resulted in 100% relapse from lungs and 80% from spleen in the TBI-166 + BDQ + OTB-658(50) group.
Resulted in 40% relapse from lungs and 60% from spleen in the TBI-166 + BDQ + OTB-658(100) group.
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Animal Model:BALB/c (female, 6-8 weeks old, 18-20 g, aerosol-infected with M. tuberculosis H37Rv)[2]
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Dosage:100 mg/kg
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Administration:p.o.; five times per week (Monday to Friday); 4 or 8 weeks
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Result:Resulted in no culture-positive lungs or spleens after 4 and 8 weeks of treatment.
Resulted in 60% relapse from lungs and 20% from spleen after 12 weeks following discontinuation of 4 weeks of treatment.
Resulted in 6.67% relapse from lungs and 0% from spleen after 12 weeks following discontinuation of 8 weeks of treatment.
Resulted in a lung CFU count close to that of the monotherapy group when combined with TBI-166.
Chemical Information
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CAS No. 2245791-50-6
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Molecular Weight 381.42
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Formula C17H20FN3O4S
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SMILES
O=C1N2C3=CC(F)=C(N4CCSCC4)C=C3OC[C@@]2([H])[C@@H](O1)CNC(C)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
OTB-658 Related Classifications
HY-187914 Related Classifications
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