| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Anti-tuberculosis
mycobacterial ATP synthase |
|---|---|
| ln Vitro |
Bedaquiline belongs to the diarylquinoline class of drugs that have demonstrated clinical effectiveness in treating drug-resistant tuberculosis. However, because of its strong inhibition of the cardiac potassium channel protein hERG, bedaquiline has the potential to cause cardiac problems. An analogue of bedaquiline, TBAJ-587, exhibits significantly lessened hERG blockade and more powerful anti-tubercular action. TBAJ-587 has an IC50 of 13 μM for inhibiting the hERG channel[1].
MIC90 against M. tuberculosis H37Rv under replicating conditions (MABA assay): 0.006 µg/mL [1] MIC90 under non-replicating conditions (LORA assay): <0.02 µg/mL [1] hERG potassium channel inhibition IC50: 13 µM [1] Aqueous solubility at pH 7.4: <0.06 µM [1] |
| ln Vivo |
In a mouse model of tuberculosis (aerosol inoculation of M.tb, treatment started 10 days post-infection), TBAJ-587 administered orally at 20 mg/kg daily for 12 days resulted in a 5.2 log reduction in lung CFU compared to vehicle control [1]
|
| Cell Assay |
MABA (Microplate Alamar Blue Assay) was used to determine the minimum inhibitory concentration for 90% inhibition (MIC90) of growth of M. tuberculosis H37Rv under aerobic (replicating) conditions [1]
LORA (Low Oxygen Recovery Assay) was used to determine MIC90 under non-replicating conditions [1] Vero cell cytotoxicity assay was performed to determine IC50 in green monkey kidney epithelial cells, but specific data for TBAJ-587 was not reported (all tested compounds except compound 9 had IC50 >10 µg/mL) [1] |
| Animal Protocol |
For efficacy study: Female mice were infected with M. tuberculosis via aerosol route. Ten days post-infection, treatment with TBAJ-587 was initiated. The compound was administered orally once daily at a dose of 20 mg/kg for 12 days. At the end of treatment, lungs were harvested and colony-forming units (CFU) were enumerated [1]
For pharmacokinetic study: Mice received a single intravenous injection and a single oral dose of TBAJ-587. Blood samples were collected at various time points to determine plasma concentrations [1] |
| ADME/Pharmacokinetics |
Human microsomal CLint: 2 µL/min/mg [1]
Mouse microsomal CLint: 18 µL/min/mg [1] IV clearance (mouse): 48 mL/min/kg [1] Volume of distribution (Vz, mouse): 95 L/kg [1] Oral AUC0-inf (mouse): 1.72 µg*h/mL [1] Oral bioavailability (mouse): 48% [1] Aqueous solubility at pH 7.4: <0.06 µM [1] clogP: 5.80 [1] |
| Toxicity/Toxicokinetics |
hERG channel inhibition IC50: 13 µM (attenuated compared to bedaquiline IC50 1.6 µM) [1]
No significant cytotoxicity in Vero cells? (compound 8 not specifically listed, but most compounds had IC50 >10 µg/mL) [1] |
| References | |
| Additional Infomation |
TBAJ-587 (compound 8) is a 3,5-dialkoxy-4-pyridyl analogue of bedaquiline with potent antituberculosis activity and reduced hERG inhibition. It was selected for preclinical development along with TBAJ-876 [1]
CAS number: 2252316-16-6 [1] Indication: drug-resistant tuberculosis [1] Mechanism of action: selective inhibition of mycobacterial ATP synthase (inferred from bedaquiline) [1] |
| Molecular Formula |
C30H33BRFN3O5
|
|---|---|
| Molecular Weight |
614.502530813217
|
| Exact Mass |
613.16
|
| Elemental Analysis |
C, 58.64; H, 5.41; Br, 13.00; F, 3.09; N, 6.84; O, 13.02
|
| CAS # |
2252316-16-6
|
| Related CAS # |
2252316-16-6;TBAJ-587 HCl;
|
| PubChem CID |
138319677
|
| Appearance |
Solid powder
|
| LogP |
5.6
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
11
|
| Heavy Atom Count |
40
|
| Complexity |
774
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CN(C)CC[C@@](C1=CC(=NC(=C1)OC)OC)([C@H](C2=C(C(=CC=C2)OC)F)C3=C(N=C4C=CC(=CC4=C3)Br)OC)O
|
| InChi Key |
JJEGOJPMKLRSPJ-POURPWNDSA-N
|
| InChi Code |
InChI=1S/C30H33BrFN3O5/c1-35(2)13-12-30(36,19-16-25(38-4)34-26(17-19)39-5)27(21-8-7-9-24(37-3)28(21)32)22-15-18-14-20(31)10-11-23(18)33-29(22)40-6/h7-11,14-17,27,36H,12-13H2,1-6H3/t27-,30-/m1/s1
|
| Chemical Name |
(1S,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-2-(2,6-dimethoxypyridin-4-yl)-4-(dimethylamino)-1-(2-fluoro-3-methoxyphenyl)butan-2-ol
|
| Synonyms |
TBAJ-587; TBAJ 587; TBAJ587
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~43.33 mg/mL (~70.51 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.17 mg/mL (3.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.17 mg/mL (3.53 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.17 mg/mL (3.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.17 mg/mL (3.53 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6273 mL | 8.1367 mL | 16.2734 mL | |
| 5 mM | 0.3255 mL | 1.6273 mL | 3.2547 mL | |
| 10 mM | 0.1627 mL | 0.8137 mL | 1.6273 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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