TBAJ-876
TBAJ-876 is an orally active diarylquinoline antimycobacterial agent. TBAJ-876 targets the c and ε subunits of Mycobacterium tuberculosis F-ATP synthase to modulate energy metabolism, and it exerts bactericidal activity against replicating Mycobacterium tuberculosis and retains activity against strains carrying Rv0678 mutations. TBAJ-876 undergoes N-demethylation in vivo to form the major active metabolite TBAJ-876-M3, which has lower lipophilicity and lower binding affinity for the hERG potassium channel. TBAJ-876 is well tolerated in BALB/c mice and significantly reduces the number of colony-forming units of Mycobacterium tuberculosis in the lungs. TBAJ-876 can be used in research related to tuberculosis and Mycobacterium abscessus lung disease.
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- CAS No.: 2332841-25-3
- 화학식: C31H37BrN4O7
- 분자량:657.55
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보관:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Vero | IC50 |
>10 μg/mL
Compound: 3; TBAJ-876
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Cytotoxicity against African green monkey Vero cells assessed as reduction in cell viability incubated for 72 hrs by MTS-PBS assay
Cytotoxicity against African green monkey Vero cells assessed as reduction in cell viability incubated for 72 hrs by MTS-PBS assay
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[PMID: 31810890] |
| Vero | IC50 |
>10 μg/mL
Compound: 46; TBAJ-876
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Cytotoxicity against African green monkey Vero cells measured after 72 hrs by MTT assay
Cytotoxicity against African green monkey Vero cells measured after 72 hrs by MTT assay
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[PMID: 30803745] |
In Vitro
TBAJ-876 (0.00025-0.063 mg/L; 1-6 d) exhibits time- and concentration-dependent bactericidal activity against actively replicating Mycobacterium tuberculosis H37Rv, with the highest concentration tested (0.063 mg/L) reducing the bacterial burden to undetectable levels by day 6[1].
TBAJ-876 (0.00025-0.063 mg/L; 21 d) shows limited activity against non-replicating Mycobacterium tuberculosis H37Rv, with only the highest tested concentration (0.063 mg/L, 16× MIC) reducing the bacterial burden by approximately 1.6 log10 CFU/mL within 3 weeks[1].
TBAJ-876 (1.38-138 μM; 5 d) exhibits in vitro bacteriostatic activity against Mycobacterium abscessus Bamboo at 3×, 30×, and 300× its MIC, inhibiting bacterial growth but not reducing bacterial counts below the initial inoculum[2].
TBAJ-876 (up to 2 μM; 3 d), when combined in vitro with commonly used anti-Mycobacterium abscessus antibiotics, exhibits additive or synergistic effects against the Mycobacterium abscessus Bamboo strain, with no antagonism observed[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
TBAJ-876 (10-30 mg/kg; p.o.; once daily; 10 consecutive days) reduces Mycobacterium abscessus bacterial loads in the lungs and spleen of infected NOD SCID mice, with efficacy comparable to bedaquiline at the 10 mg/kg dose[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD.CB17-Prkdcscid/NCrCrl (NOD SCID) (8-week-old female, intranasal infection with Mycobacterium abscessus subsp. abscessus K21)[2]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:p.o.; once daily; 10 consecutive days
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Result:Achieved in vivo efficacy against M.
abscessus comparable to bedaquiline, reducing bacterial loads in the lungs and spleen relative to untreated controls at 10 mg/kg.
Demonstrated increased efficacy in reducing bacterial loads in both lungs and spleen compared to the 10 mg/kg dose at 30 mg/kg, though this difference was not statistically significant.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2332841-25-3
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Appearance Solid
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분자량 657.55
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화학식 C31H37BrN4O7
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Color White to off-white
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SMILES
COC1=NC(OC)=C(OC)C([C@H](C2=CC(C=C(Br)C=C3)=C3N=C2OC)[C@@](C4=CC(OC)=NC(OC)=C4)(O)CCN(C)C)=C1
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
순도&문서
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Data Sheet (281 KB)
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SDS (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Mudde SE, et al. Relative Contributions of the Novel Diarylquinoline TBAJ-876 and its Active Metabolite to the Bactericidal Activity in a Murine Model of Tuberculosis. J Infect Dis. 2024;230(6):e1366-e1374. [Content Brief]
[2]. Sarathy JP, et al. TBAJ-876, a 3,5-Dialkoxypyridine Analogue of Bedaquiline, Is Active against Mycobacterium abscessus. Antimicrob Agents Chemother. 2020;64(4):e02404-19. Published 2020 Mar 24. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
TBAJ-876 Related Classifications
HY-128866 Related Classifications
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Keywords
- TBAJ-876
- 2332841-25-3
- TBAJ876
- TBAJ 876
- Bacterial
- ATP Synthase
- Mycobacterium tuberculosis
- Mycobacterium abscessus
- ATP synthase
- Mycobacterium tuberculosis F-ATP synthase subunits c
- Rv0678 mutations
- BALB/c mice
- hERG potassium channels
- Mycobacterium tuberculosis Beijing VN2002-1585
- Mycobacterium tuberculosis F-ATP synthase subunits ε
- NOD SCID mice
- Inhibitor
- inhibitor
- inhibit