TBAJ-876
TBAJ-876 is an orally active diarylquinoline anti-Mycobacterium agent. TBAJ-876 regulates energy metabolism by targeting the c and ε subunits of Mycobacterium tuberculosis F-ATP synthase, exerts bactericidal activity against replicating Mycobacterium tuberculosis, and retains activity against strains carrying the Rv0678 mutation. TBAJ-876 undergoes N-demethylation in vivo to form its major active metabolite TBAJ-876-M3, which has lower lipophilicity and hERG potassium channel binding affinity. TBAJ-876 is well tolerated in BALB/c mice and significantly reduces the colony-forming units of Mycobacterium tuberculosis in the lungs. In addition, TBAJ-876 exhibits inhibitory activity against Mycobacterium abscessus, reduces bacterial loads in the lungs and spleens of infected mice, and shows no antagonistic effect when used in combination with common antibiotics. TBAJ-876 can be used in studies related to tuberculosis and Mycobacterium abscessus pulmonary diseases.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- CAS 番号: 2332841-25-3
- 分子式: C31H37BrN4O7
- 分子量:657.55
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保管条件:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
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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] |
TBAJ-876 (0.004-0.016 mg/L) has potent in vitro bacteriostatic activity against Mycobacterium tuberculosis H37Rv (MIC 0.008-0.016 mg/L) and Mycobacterium tuberculosis Beijing VN 2002-1585 (MIC 0.004 mg/L)[1].
TBAJ-876 (0.0001-0.016 mg/L; 10 days) shows no interaction with its metabolite M3 when tested against Mycobacterium tuberculosis Beijing VN 2002-1585[1].
TBAJ-876 (0.00025-0.063 mg/L; 1-6 days) demonstrates time- and concentration-dependent bactericidal activity against actively replicating Mycobacterium tuberculosis H37Rv, with the highest tested concentration (0.063 mg/L) reducing bacterial load to undetectable levels by day 6[1].
TBAJ-876 (0.00025-0.063 mg/L; up to 21 days) has limited activity against nonreplicating Mycobacterium tuberculosis H37Rv, with only the highest tested concentration (0.063 mg/L, 16× MIC) reducing bacterial load by ~1.6 log10 CFU/mL over 3 weeks[1].
TBAJ-876 (1.38-138 μM; 5 days) exerts bacteriostatic activity against M. abscessus Bamboo in vitro at concentrations of 3x, 30x, and 300x its MIC, inhibiting growth without reducing bacterial counts below the initial inoculum[2].
TBAJ-876 (0-2 μM; 3 days) exhibits additive or synergistic in vitro interactions with commonly used anti-M. abscessus antibiotics against M. abscessus Bamboo, with no observed antagonism[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
化学情報
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CAS 番号 2332841-25-3
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性状 Solid
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分子量 657.55
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分子式 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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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
純度とドキュメンテーション
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データシート (280 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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取扱説明書 (2659 KB)
参考文献
[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
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
TBAJ-876 関連分類
HY-128866 関連分類
Powered by Bioz
- TBAJ-876
- 2332841-25-3
- TBAJ876
- TBAJ 876
- Bacterial
- 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