| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
(Rac)-TBAJ-876 targets ATP synthase, an enzyme essential for energy generation in TB mycobacteria. By inhibiting this enzyme, the compound depletes ATP, leading to bacterial cell death. It belongs to the same drug class as bedaquiline, the first approved DARQ, but has improved potency and safety.
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| ln Vitro |
In vitro, (Rac)-TBAJ-876 has potent antimycobacterial activity against M. tuberculosis H37Rv and clinical isolates, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, with MIC values in the nanomolar range (0.016-0.06 ug/mL). It is more potent than bedaquiline against some resistant strains and has a lower cytotoxicity against Vero cells (IC₅0 > 100 uM).
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| ln Vivo |
In vivo, (Rac)-TBAJ-876 has been evaluated in a phase 1 first-in-human study in 137 healthy adults. Single doses up to 800 mg and multiple doses up to 200 mg for 14 days were well-tolerated, with no deaths, serious adverse events, or clinically significant QTc prolongation. It exhibits multicompartmental PK with a long terminal half-life and dose-proportional exposures.
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| Enzyme Assay |
For ATP synthesis inhibition assays, M. tuberculosis membranes are incubated with (Rac)-TBAJ-876 (0.01-10 uM) and NADH (for coupled assay). ATP depletion is measured by bioluminescence. MICs are determined by broth microdilution in 7H9 medium. For selectivity, the compound is tested against a panel of human cell lines (IC₅0 > 100 uM).
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| Cell Assay |
Not applicable. For antimycobacterial activity, M. tuberculosis H37Rv is cultured in 7H9 medium in 96-well plates and treated with (Rac)-TBAJ-876 (0.001-10 ug/mL). After 7-14 days, growth is assessed by OD₆00 or by resazurin reduction. MIC is defined as the lowest concentration with no visible growth.
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| Animal Protocol |
For in vivo efficacy in TB mouse models, C3HeB/FeJ mice are infected with M. tuberculosis via aerosol. (Rac)-TBAJ-876 (12.5-50 mg/kg) is administered orally once daily. Lung and spleen CFU are measured after 4-8 weeks of treatment. Human trials are ongoing to evaluate efficacy.
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| ADME/Pharmacokinetics |
(Rac)-TBAJ-876 is orally bioavailable. In humans, single doses up to 800 mg show dose-proportional exposure, with Tmax 4-6 h and a long terminal half-life (>240 h), yielding quantifiable concentrations for up to 10 weeks. Food increases tablet exposure (2-fold). It is a substrate of CYP3A4 and an inhibitor of P-gp.
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| Toxicity/Toxicokinetics |
In phase 1 trials, (Rac)-TBAJ-876 was well-tolerated. No deaths or serious adverse events. No QTc prolongation. Common adverse events: headache, nausea, diarrhea. No significant drug-induced liver injury. Safety in TB patients is under investigation.
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| References | |
| Additional Infomation |
(Rac)-TBAJ-876 is the racemic form of the second-generation diarylquinoline TBAJ-876 (sorfequiline) in clinical development for tuberculosis. It has greater activity than bedaquiline and a better safety profile. Not FDA-approved; phase 2/3 trials ongoing. For research use only.
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| Molecular Formula |
C31H37BRN4O7
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|---|---|
| Molecular Weight |
657.55
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| Exact Mass |
656.185
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| CAS # |
2131784-39-7
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| PubChem CID |
130406771
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
43
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| Complexity |
836
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C)CCC(C1=CC(=NC(=C1)OC)OC)(C(C2=CC(=NC(=C2OC)OC)OC)C3=C(N=C4C=CC(=CC4=C3)Br)OC)O
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| InChi Key |
HHDDKDPLFXIPBX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H37BrN4O7/c1-36(2)12-11-31(37,19-15-24(38-3)34-25(16-19)39-4)27(21-17-26(40-5)35-30(43-8)28(21)41-6)22-14-18-13-20(32)9-10-23(18)33-29(22)42-7/h9-10,13-17,27,37H,11-12H2,1-8H3
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| Chemical Name |
1-(6-bromo-2-methoxyquinolin-3-yl)-2-(2,6-dimethoxy-4-pyridinyl)-4-(dimethylamino)-1-(2,3,6-trimethoxy-4-pyridinyl)butan-2-ol
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~1.43 mg/mL (~2.17 mM; with ultrasonication (<60°C))
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5208 mL | 7.6040 mL | 15.2080 mL | |
| 5 mM | 0.3042 mL | 1.5208 mL | 3.0416 mL | |
| 10 mM | 0.1521 mL | 0.7604 mL | 1.5208 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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