| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Enoyl-acyl carrier protein (ACP) reductase FabI of Staphylococcus aureus and Escherichia coli (specific inhibitor). [1]
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| ln Vitro |
MUT056399 (Fab-001) is a highly efficient inhibitor of the new FabI enzyme in Staphylococcus aureus and Escherichia coli. MUT056399 is very effective against Staphylococcus aureus strains, including methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), linezolid-resistant strains, and multidrug-resistant strains, having a MIC90 between Between 0.03 and 0.12 μg/ml. MUT056399 is also active against coagulase-negative staphylococci, with MIC90 ranging from 0.12 to 4 μg/ml. MUT056399 was extremely effective against 118 S. aureus strains investigated, including MSSA and MRSA isolates as well as linezolid-resistant and multidrug-resistant strains, with MIC90 ≤0.03 to 0.12 μg/ml.
MUT056399 exhibited potent in vitro antibacterial activity against Staphylococcus aureus, with MIC₉₀ values between 0.03 and 0.12 μg/ml against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), linezolid-resistant, and multidrug-resistant strains. [1] MUT056399 was active against coagulase-negative staphylococci, with MIC₉₀ values between 0.12 and 4 μg/ml. [1] MUT056399 showed a narrow spectrum consistent with specific FabI inhibition: it was active against Gram-negative bacilli containing FabI (e.g., E. coli, Klebsiella spp., H. influenzae), but not active against bacteria using alternative enoyl-ACP reductases like FabK (e.g., Streptococcus pneumoniae, Enterococcus). [1] Time-kill kinetics experiments against S. aureus showed that MUT056399 at 64 times the MIC was bactericidal (achieving ≥3-log₁₀ killing), while at 4 and 16 times the MIC it was bacteriostatic. In the presence of 50% human serum, the bactericidal activity was slowed. [1] The spontaneous resistance frequency for S. aureus to MUT056399 was low, between 2.5 x 10⁻⁹ and 7 x 10⁻⁹ at 4 times the MIC. [1] All analyzed S. aureus clones with reduced susceptibility to MUT056399 contained mutations in the fabI gene (amino acid substitutions A95V, F204S, I193F, or Y147H), which also conferred decreased susceptibility to triclosan (another FabI inhibitor). [1] |
| ln Vivo |
Subcutaneous injection of MUT056399 (Fab-001) shields mice from fatal systemic infection caused by strains of MRSA, MSSA, and vancomycin-intermediate Staphylococcus aureus (50% effective dose range 19.3 mg/kg/day to 49.6 mg/kg/day). Similar treatment with MUT056399 decreased MRSA and MSSA bacterial proliferation in the thighs of immunocompetent mice in a nonneutropenic mouse thigh infection model.
In a murine systemic lethal infection model, a single subcutaneous administration of MUT056399 protected mice against infection by various S. aureus strains (MSSA, MRSA, vancomycin-intermediate S. aureus). The mean 50% effective dose (ED₅₀) values ranged from 19.3 to 49.6 mg/kg/day. [1] In a non-neutropenic murine thigh infection model, MUT056399 administered subcutaneously significantly reduced the bacterial load of MSSA and MRSA in a dose-dependent manner, with mean static doses ranging from 40 to 45.5 mg/kg/day. At a single dose of 50 mg/kg, its activity in reducing bacterial burden was comparable to that of linezolid. [1] |
| Animal Protocol |
Systemic lethal infection model: Groups of six female Swiss mice (6 weeks old) were infected intraperitoneally with a lethal inoculum of S. aureus. MUT056399 was administered subcutaneously in a single dose at various concentrations. Mouse survival was assessed at 48 hours post-infection to determine the ED₅₀. [1]
Thigh infection model: Immunocompetent mice were infected intramuscularly in the thigh with S. aureus. MUT056399 was administered subcutaneously. Bacterial loads in the thighs were determined 20 hours post-infection. [1] |
| References |
[1]. Escaich S, et al. The MUT056399 inhibitor of FabI is a new antistaphylococcal compound. Antimicrob Agents Chemother. 2011 Oct;55(10):4692-7.
[2]. Schiebel J, et al. An ordered water channel in Staphylococcus aureus FabI: unraveling the mechanism of substrate recognitionand reduction. Biochemistry. 2015 Mar 17;54(10):1943-55. |
| Additional Infomation |
MUT056399 (also known as FAB001) is an aryloxyphenol synthetic compound designed as a specific inhibitor of bacterial FabI enzyme based on structural data of FabI binding to triclosan. [1] FabI is a NADH-dependent trans-2-enoyl-acyl carrier protein reductase, a key enzyme in the bacterial type II fatty acid synthesis pathway, essential for bacterial growth, and has no corresponding counterpart in eukaryotes. [1] The antibacterial spectrum of MUT056399 is specific to bacteria that rely on FabI for fatty acid synthesis, which distinguishes it from broad-spectrum antibacterial agents such as triclosan and other Staphylococcus-specific FabI inhibitors. [1]
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| Molecular Formula |
C15H13F2NO3
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|---|---|
| Molecular Weight |
293.27
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| Exact Mass |
293.086
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| CAS # |
1269055-85-7
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| PubChem CID |
44208849
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
373.8±42.0 °C at 760 mmHg
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| Flash Point |
179.9±27.9 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.584
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| LogP |
3.58
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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 |
4
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| Heavy Atom Count |
21
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| Complexity |
369
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC1=CC(O)=C(OC2=CC=C(C(N)=O)C=C2F)C=C1F
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| InChi Key |
QUHARGDBJJUOEB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H13F2NO3/c1-2-8-6-12(19)14(7-10(8)16)21-13-4-3-9(15(18)20)5-11(13)17/h3-7,19H,2H2,1H3,(H2,18,20)
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| Chemical Name |
4-(4-ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzamide
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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 : ≥ 31 mg/mL (~105.70 mM)
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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 | 3.4098 mL | 17.0491 mL | 34.0983 mL | |
| 5 mM | 0.6820 mL | 3.4098 mL | 6.8197 mL | |
| 10 mM | 0.3410 mL | 1.7049 mL | 3.4098 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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