| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Thiolactomycin targets bacterial type II fatty acid synthase (FAS-II). It specifically inhibits FabB (β-ketoacyl-ACP synthase I) and FabF (β-ketoacyl-ACP synthase II), key enzymes in the fatty acid elongation cycle. By inhibiting these enzymes, Thiolactomycin blocks fatty acid and mycolic acid biosynthesis. The compound also inhibits D-amino acid oxidase (DAO) and D-aspartate oxidase (DDO). This dual inhibition contributes to its antibacterial and antimalarial activities.
|
|---|---|
| ln Vitro |
Thiolactomycin demonstrates in vitro antibacterial activity against Gram-negative anaerobes. It inhibits the growth of malaria parasites and trypanosomes. The compound's inhibition of FabB and FabF enzymes disrupts fatty acid synthesis, which is essential for bacterial cell membrane integrity and viability. As a thiotetronate antibiotic, it serves as a model compound for studying thiotetronate antibiotics. Specific in vitro data, including IC50 values against various bacterial strains and detailed assay conditions, are not extensively provided in the available literature.
|
| ln Vivo |
Thiolactomycin demonstrates in vivo activity as an orally active antibiotic. Its inhibition of fatty acid and mycolic acid biosynthesis makes it a promising candidate for treating tuberculosis. The compound also inhibits malaria and trypanosomes in vivo. As a FabB inhibitor, it disrupts bacterial fatty acid synthesis, leading to bactericidal effects. Specific in vivo efficacy data, including dosing regimens, animal models, and detailed results, are not extensively provided in the available literature. The compound's oral bioavailability makes it suitable for oral administration.
|
| Enzyme Assay |
In vitro enzyme assays for Thiolactomycin involve measuring FabB and FabF (β-ketoacyl-ACP synthase) activity. Bacterial FabB/FabF enzymes are incubated with acyl-ACP substrates and malonyl-CoA in the presence of varying concentrations of Thiolactomycin (typically 0.1-100 μM). The reaction is initiated by addition of enzyme and terminated by acidification. Product formation (β-ketoacyl-ACP) is quantified by spectrophotometric methods or by using radiolabeled substrates. IC50 values are calculated from concentration-response curves. For DAO and DDO assays, enzyme activity is measured by monitoring hydrogen peroxide production or by using fluorometric substrates.
|
| Cell Assay |
For in vitro cell-based assays, bacterial strains (e.g., Gram-negative anaerobes, Mycobacterium tuberculosis) are cultured in appropriate medium. Bacteria are treated with Thiolactomycin at various concentrations (typically 0.1-100 μM) for 18-24 hours. Minimum inhibitory concentrations (MICs) are determined by broth microdilution or agar dilution methods. Bacterial growth is measured by optical density at 600 nm. For antimalarial assays, Plasmodium falciparum cultures are treated with Thiolactomycin, and parasite growth is assessed by measuring [³H]hypoxanthine incorporation or by microscopy. Cytotoxicity against mammalian cells is assessed using MTT or similar assays.
|
| Animal Protocol |
In vivo animal studies for Thiolactomycin would typically use mouse models of bacterial infection (e.g., tuberculosis, sepsis) or malaria. Thiolactomycin is administered orally or intraperitoneally at doses determined from pharmacokinetic studies. Bacterial load in tissues (e.g., lungs, spleen) is measured by colony-forming unit (CFU) assays. For malaria models, parasitemia is monitored by blood smears. Survival and body weight are monitored. Specific protocols using Thiolactomycin are not extensively documented in the available literature. The compound's oral activity makes it suitable for oral administration in animal models.
|
| ADME/Pharmacokinetics |
Thiolactomycin has a molecular formula of C11H14O2S and molecular weight of 210.29. The compound is orally active, suggesting good oral bioavailability. It is a thiotetronate antibiotic that serves as a model compound for studying thiotetronate antibiotics. Detailed pharmacokinetic parameters (absorption, distribution, metabolism, excretion, half-life, Cmax, Tmax, AUC) are not extensively characterized in the available literature. As a small molecule antibiotic, it would be expected to distribute well into tissues.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for Thiolactomycin are not extensively provided in the available literature. As an antibacterial agent targeting bacterial fatty acid synthesis, it would be expected to have selective toxicity against bacteria with minimal effects on mammalian cells, which use type I fatty acid synthase (FAS-I) rather than FAS-II. The compound's inhibition of DAO and DDO may have additional effects. Standard toxicology assessments would be required for therapeutic development, including acute, subchronic, and chronic toxicity studies, as well as genotoxicity and reproductive toxicity evaluations.
|
| Additional Infomation |
According to reports, both Streptomyces and Nocardia contain thiolactamase, and relevant data are available for reference.
Thiolactomycin is an orally active bacterial type II fatty acid synthase (FAS-II) inhibitor with antibacterial and antimalarial activities. It is a thiotetronate antibiotic that selectively targets bacterial fatty acid biosynthesis. The compound inhibits FabB and FabF (β-ketoacyl-ACP synthases), crucial enzymes in the fatty acid synthesis pathway. Thiolactomycin is active against Gram-negative anaerobes and also inhibits malaria and trypanosomes. It inhibits fatty acid and mycolic acid biosynthesis, making it a promising candidate for treating tuberculosis. Thiolactomycin also inhibits D-amino acid oxidase and D-aspartate oxidase. No approved therapeutic status is reported. |
| Molecular Formula |
C11H14O2S
|
|---|---|
| Molecular Weight |
210.292662143707
|
| Exact Mass |
210.071
|
| CAS # |
82079-32-1
|
| PubChem CID |
135403829
|
| Appearance |
White to light yellow solid powder
|
| Density |
1.214g/cm3
|
| Boiling Point |
319.2ºC at 760 mmHg
|
| Flash Point |
146.8ºC
|
| Index of Refraction |
1.632
|
| LogP |
2.982
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
14
|
| Complexity |
352
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC1=C(C(SC1=O)(C)C=C(C)C=C)O
|
| InChi Key |
SYQNUQSGEWNWKV-XUIVZRPNSA-N
|
| InChi Code |
InChI=1S/C11H14O2S/c1-5-7(2)6-11(4)9(12)8(3)10(13)14-11/h5-6,12H,1H2,2-4H3/b7-6+/t11-/m1/s1
|
| Chemical Name |
(5R)-4-hydroxy-3,5-dimethyl-5-[(1E)-2-methylbuta-1,3-dienyl]thiophen-2-one
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 4.7553 mL | 23.7767 mL | 47.5534 mL | |
| 5 mM | 0.9511 mL | 4.7553 mL | 9.5107 mL | |
| 10 mM | 0.4755 mL | 2.3777 mL | 4.7553 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
