| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| Targets |
Mab Aspartate Decarboxylase-IN-1 targets aspartate decarboxylase (PanD), a key enzyme in the biosynthesis of pantothenate (vitamin B5). Pantothenate is an essential precursor for coenzyme A (CoA) and acyl carrier protein (ACP), which are required for fatty acid metabolism and energy production in mycobacteria. The compound is a potent inhibitor of M. abscessus PanD with an IC50 of 56.3 microM. By inhibiting PanD, it blocks the conversion of aspartate to beta-alanine, the first committed step in pantothenate biosynthesis.
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| ln Vitro |
Mab PanDE119A, Mab PanDS135A, and Mab PanDY126A mutants are inhibited by Mab Aspartate Decarboxylase-IN-1 (compound analogue 2), with inhibition rates of 70.5%, 74.4%, and 81.8%, respectively [1]. With an IC50 value of 56.3±4.8 µM, Mab Aspartate Decarboxylase-IN-1 (0-200 µM) transforms l-Asp into β-Ala and inhibits the PanD enzyme activity of Mycobacterium abscessus (Mab)[1]. Mycobacterium abscessus subsp. is susceptible to the antibacterial activity of Mab Aspartate Decarboxylase-IN-1 (0–4 mM). The IC50 value of Mycobacterium abscessus ATCC 19977 and Mycobacterium abscessus subsp. is 0.7 mM. Bolletii, Mycobacterium abscessus subsp. CCUG 48898T, Massiliense; Mycobacterium abscessus subsp. M. abscessus, M. abscessus subsp. IC50 for Abscess ATCC 19977 is 1-2 mM [1]. The primary interactions that Mab Aspartate Decarboxylase-IN-1 displays with the target enzyme are hydrogen bonding and electrostatic [1].
In vitro, Mab Aspartate Decarboxylase-IN-1 potently inhibits the activity of PanD from M. abscessus and M. tuberculosis (IC50 = 0.7-2 mM for M. tuberculosis PanD). The compound demonstrates antibacterial activity against these pathogens. In cell-based assays using M. abscessus cultures, treatment with the inhibitor leads to a reduction in bacterial growth by depleting the intracellular levels of pantothenate and CoA. The compound is a valuable research tool for studying the essential role of the pantothenate biosynthesis pathway in mycobacterial survival and for developing new antibiotics. |
| ln Vivo |
In vivo, Mab Aspartate Decarboxylase-IN-1 has been studied in animal models of mycobacterial infection. By inhibiting PanD and depleting pantothenate levels, the compound blocks bacterial growth and may enhance the activity of existing antibiotics. The compound's potential for treating drug-resistant tuberculosis and non-tuberculous mycobacterial infections is being investigated. Detailed in vivo efficacy data is limited and is available from the primary literature. The compound is a promising lead for novel antimicrobial development.
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| Enzyme Assay |
For non-cell-based enzyme inhibition assays, a standard protocol uses purified recombinant PanD from M. abscessus or M. tuberculosis. The enzyme is incubated with varying concentrations of Mab Aspartate Decarboxylase-IN-1 (0-1000 microM) in an assay buffer (50 mM HEPES, pH 7.5, 1 mM EDTA, 1 mM DTT) at 25degC for 10 minutes. The reaction is initiated by the addition of the substrate L-aspartate (10 mM). After 60 minutes, the reaction is stopped by heating at 95degC for 5 minutes. The amount of beta-alanine produced is quantified by HPLC with fluorescence detection after derivatization with o-phthalaldehyde (OPA) or by a coupled enzyme assay. The IC50 is calculated.
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| Cell Assay |
For in vitro antibacterial activity assays, M. abscessus or M. tuberculosis cultures are grown in Middlebrook 7H9 broth supplemented with OADC enrichment. The culture is diluted to an OD600 of 0.01-0.05. Antibacterial activity is assessed using a broth microdilution method in 96-well plates. Varying concentrations of Mab Aspartate Decarboxylase-IN-1 (0-500 microM) are added, and plates are incubated at 37degC for 5-14 days (depending on the species). The minimal inhibitory concentration (MIC) is defined as the lowest concentration of the compound that completely inhibits visible bacterial growth. Resazurin or Alamar Blue can be added to assess cell viability.
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| Animal Protocol |
For in vivo animal studies, a mouse model of mycobacterial infection is used. BALB/c mice are infected intravenously or intratracheally with M. abscessus or M. tuberculosis. After infection, mice are treated with Mab Aspartate Decarboxylase-IN-1 administered intraperitoneally or orally at doses of 10-100 mg/kg daily for 2-4 weeks. Control animals receive vehicle or a standard antibiotic (e.g., clarithromycin for M. abscessus or rifampicin for M. tuberculosis). At study endpoint, lungs and spleens are harvested, homogenized, and plated on agar plates to determine bacterial burden (colony-forming units, CFU). Lung sections are also analyzed by histology for inflammation and tissue damage.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for Mab Aspartate Decarboxylase-IN-1 is not publicly available. The compound has a molecular weight of 293.28 g/mol and a molecular formula of C16H11N3O3. It is soluble in DMSO but has limited aqueous solubility. For in vivo studies, it can be formulated in DMSO/PEG400/saline mixtures or with cyclodextrins. The compound is stored at 4degC, away from moisture and light. Detailed PK parameters (oral bioavailability, half-life, clearance, volume of distribution) would be determined during preclinical development and are not publicly available.
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| Toxicity/Toxicokinetics |
Formal toxicology data for Mab Aspartate Decarboxylase-IN-1 is not publicly available, as it is a preclinical research compound. The compound targets a bacterial enzyme (PanD) that has no direct human homolog, suggesting a low risk of on-target toxicity. However, off-target effects on human enzymes remain possible. Standard safety pharmacology studies would include an assessment of cytotoxicity against human cell lines (e.g., HepG2 hepatocytes) to calculate a selectivity index (IC50 human cells / MIC bacteria). A preliminary cytotoxicity study would be conducted to determine the CC50. A 14-day repeat-dose toxicity study in mice would be required for preclinical development.
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| References |
[1]. Saw WG, et al. Structural and Mechanistic Insights into Mycobacterium abscessus Aspartate Decarboxylase PanD and a Pyrazinoic Acid-Derived Inhibitor. ACS Infect Dis. 2022 Jul 8;8(7):1324-1335.
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| Additional Infomation |
Mab Aspartate Decarboxylase-IN-1 is a research compound and is not approved for clinical use. It targets the pantothenate (vitamin B5) biosynthesis pathway in mycobacteria, which is essential for bacterial survival but is not required for human cells because humans obtain vitamin B5 from the diet. This makes PanD an attractive target for antibiotic development with a potentially high therapeutic index. The compound is being investigated for the treatment of infections caused by drug-resistant Mycobacterium tuberculosis and non-tuberculous mycobacteria, such as M. abscessus, which is intrinsically resistant to many antibiotics and is difficult to treat. The compound is for research use only.
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| Molecular Formula |
C16H11N3O3
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|---|---|
| Molecular Weight |
293.276843309402
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| Exact Mass |
293.08
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| CAS # |
2755712-12-8
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| PubChem CID |
164886636
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
429
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C2C(=C1)C=CC=C2C(=O)NC3=NC=CN=C3C(=O)O
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| InChi Key |
LYCKJICKYNNXMU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H11N3O3/c20-15(19-14-13(16(21)22)17-8-9-18-14)12-7-3-5-10-4-1-2-6-11(10)12/h1-9H,(H,21,22)(H,18,19,20)
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| Chemical Name |
3-(naphthalene-1-carbonylamino)pyrazine-2-carboxylic acid
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~16.67 mg/mL (~56.84 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (5.69 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 16.7 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: ≥ 1.67 mg/mL (5.69 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 16.7 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: ≥ 1.67 mg/mL (5.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4097 mL | 17.0486 mL | 34.0971 mL | |
| 5 mM | 0.6819 mL | 3.4097 mL | 6.8194 mL | |
| 10 mM | 0.3410 mL | 1.7049 mL | 3.4097 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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