| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
Mtb ATP synthase-IN-1 targets the ATP synthase enzyme in Mycobacterium tuberculosis, which is essential for bacterial energy production. ATP synthase is a key enzyme in the oxidative phosphorylation pathway that generates ATP from ADP and inorganic phosphate. By inhibiting ATP synthase, the compound disrupts the bacterial energy metabolism, leading to bacterial death. This target is distinct from conventional anti-TB drugs such as isoniazid and rifampicin, making it a promising candidate for combating drug-resistant TB. The compound has an MIC of 0.452-0.499 μg/mL against Mtb.
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| ln Vitro |
In vitro, Mtb ATP synthase-IN-1 is a potent inhibitor of Mycobacterium tuberculosis with MIC values of 0.452-0.499 μg/mL. It shows low cytotoxicity in Vero cells with an IC50 > 64 μg/mL, indicating a favorable selectivity index (SI > 128). The compound has good metabolic stability in vitro, suggesting it is not rapidly degraded by metabolic enzymes. Its mechanism of action involves inhibition of ATP synthesis, leading to depletion of cellular ATP and bacterial death.
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| ln Vivo |
Mtb ATP synthase-IN-1 shows acceptable oral bioavailability and good metabolic stability at 50 mg/kg orally and 5 mg/kg intravenously (single dose) [1]. Mtb ATP synthase-IN-1 pharmacokinetic parameters in male CD-1 mice [1]. PO (50 mg/kg) IV (5 mg/kg) Cmax (ng/mL) 1333 1241 Tmax (h) 0.83 T1/2 (h) 0.51 0.33 AUC0-t (ng/mL·h) 2197 1667 AUC0-∞ (ng/mL·h) 2198 1672 MRT0-∞ (ng/mL) 1.36 0.28 CL (mL/min/kg) 51.4 F (%) 13.1
In vivo, Mtb ATP synthase-IN-1 shows acceptable oral bioavailability and good metabolic stability. In pharmacokinetic studies in male CD-1 mice, oral administration at 50 mg/kg achieved a Cmax of 1333 ng/mL, Tmax of 0.83 h, and AUC0-t of 2197 ng/mL·h. Intravenous administration at 5 mg/kg showed a Cmax of 1241 ng/mL, t1/2 of 0.33 h, and AUC0-t of 1667 ng/mL·h. The oral bioavailability (F) was 13.1%. The compound demonstrates potential for oral administration in TB treatment. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Mtb ATP synthase-IN-1 typically involve ATP synthase activity assays using purified Mtb ATP synthase enzyme or inverted membrane vesicles from Mtb. The assay is performed in buffer containing ATP, MgCl2, and the enzyme. ATP hydrolysis or synthesis activity is measured using a coupled enzyme assay (e.g., pyruvate kinase/lactate dehydrogenase) or by monitoring NADH oxidation spectrophotometrically at 340 nm. The compound (typically 0.001-100 μg/mL) is incubated with the enzyme for 10-30 minutes before adding substrate. The IC50 is determined from dose-response curves.
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| Cell Assay |
In vitro cellular assays for Mtb ATP synthase-IN-1 use Mycobacterium tuberculosis cultures (H37Rv strain) in Middlebrook 7H9 broth supplemented with OADC. Bacteria are grown to mid-log phase and treated with various concentrations of the compound (typically 0.01-100 μg/mL) for 5-7 days at 37°C. MIC is determined as the lowest concentration that inhibits visible bacterial growth. For cytotoxicity assessment, Vero cells are cultured in DMEM with 10% FBS and treated with various concentrations of the compound for 48-72 hours, and cell viability is assessed using MTT assays.
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| Animal Protocol |
Animal/Disease Models: Male CD-1 mouse[1]
Doses: 50 and 5 mg/kg Doses: oral 50mg/kg, intravenous (iv) (iv)injection 5mg/kg; single dose (pharmacokinetic/PK/PK analysis) Experimental Results: demonstrated good metabolic stability and acceptable oral bioavailability. In vivo animal studies with Mtb ATP synthase-IN-1 typically use mouse models of TB infection. Male CD-1 mice are used for pharmacokinetic studies. The compound is administered orally (50 mg/kg) or intravenously (5 mg/kg) as a single dose. Blood samples are collected at various time points (0.083, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose) for PK analysis. For efficacy studies, mice are infected with Mtb and treated with the compound orally for 4-8 weeks, followed by assessment of bacterial load in lungs and spleen. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Mtb ATP synthase-IN-1: In male CD-1 mice, oral administration at 50 mg/kg: Cmax = 1333 ng/mL, Tmax = 0.83 h, AUC0-t = 2197 ng/mL·h, AUC0-∞ = 2198 ng/mL·h, MRT0-∞ = 1.36 h, F = 13.1%. Intravenous administration at 5 mg/kg: Cmax = 1241 ng/mL, t1/2 = 0.33 h, AUC0-t = 1667 ng/mL·h, AUC0-∞ = 1672 ng/mL·h, MRT0-∞ = 0.28 h, CL = 51.4 mL/min/kg. The compound shows good metabolic stability and acceptable oral bioavailability.
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| Toxicity/Toxicokinetics |
The toxicity profile of Mtb ATP synthase-IN-1 shows low cytotoxicity. In Vero cells, the IC50 is greater than 64 μg/mL, indicating a favorable safety margin. The compound is for research use only and not for human therapeutic use. Standard toxicity studies would include acute and subchronic oral toxicity in rodents, with monitoring of body weight, clinical signs, hematology, clinical chemistry, and histopathology. No specific genotoxicity or cardiotoxicity data are reported. The low cytotoxicity suggests a good therapeutic index.
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| References | |
| Additional Infomation |
Mtb ATP synthase-IN-1 (CAS 2642394-38-3, compound 6ab) is a potent inhibitor of Mycobacterium tuberculosis ATP synthase with MIC values of 0.452-0.499 μg/mL. It shows low cytotoxicity (Vero IC50 > 64 μg/mL) and acceptable oral bioavailability (F = 13.1% in mice) with good metabolic stability. The compound targets a novel mechanism distinct from existing anti-TB drugs, making it a promising candidate for research on drug-resistant tuberculosis. It is available for research purposes only and is not approved for clinical use. References include preclinical pharmacokinetic data in CD-1 mice.
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| Molecular Formula |
C17H13N3O4
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| Molecular Weight |
323.302823781967
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| Exact Mass |
323.09
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| CAS # |
2642394-38-3
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| PubChem CID |
162662421
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| Appearance |
Off-white to light brown solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
24
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| Complexity |
562
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=O)C(NCC2=NC=CC=C2)=C(NC2=CC=C3OCOC3=C2)C1=O
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| InChi Key |
ZEYYGLIHJGBVNS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H13N3O4/c21-16-14(19-8-11-3-1-2-6-18-11)15(17(16)22)20-10-4-5-12-13(7-10)24-9-23-12/h1-7,19-20H,8-9H2
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| Chemical Name |
3-(1,3-benzodioxol-5-ylamino)-4-(pyridin-2-ylmethylamino)cyclobut-3-ene-1,2-dione
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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 : ~125 mg/mL (~386.64 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0931 mL | 15.4655 mL | 30.9310 mL | |
| 5 mM | 0.6186 mL | 3.0931 mL | 6.1862 mL | |
| 10 mM | 0.3093 mL | 1.5466 mL | 3.0931 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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