| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| 50mg | |||
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| Other Sizes |
| Targets |
The LolCDE ABC transporter complex in Gram-negative bacteria, which is essential for the trafficking of lipoproteins from the inner to the outer membrane.
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| ln Vitro |
In vitro, G0507 is a potent inhibitor of E. coli growth. By inhibiting the LolCDE transporter, it disrupts the localization of lipoproteins to the outer membrane. This mislocalization triggers the extracytoplasmic σE stress response, a signaling pathway that detects misfolded proteins in the bacterial envelope. This compound is highly selective for its target and serves as an effective chemical probe.
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| ln Vivo |
G0507 has been shown to induce the extracytoplasmic σE stress response in E. coli cells. The σE stress response is a key indicator of cell envelope dysfunction. By using G0507, researchers can dissect the complex biological processes of lipoprotein trafficking and the subsequent stress signaling pathways in live Gram-negative bacteria. It allows for temporal control over target inhibition.
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| Enzyme Assay |
While G0507 is not typically used in receptor binding assays, a high-throughput screening (HTS) assay could be designed. The LolCDE transporter is an ATPase; its activity can be measured in a cell-free system by incubating purified LolCDE with its substrate (Lpp or other lipoproteins) and ATP. The amount of inorganic phosphate released from ATP hydrolysis can be detected using a colorimetric malachite green assay. G0507 can be added to this reaction to determine its IC₅0 for ATPase inhibition.
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| Cell Assay |
The primary in vitro cell-based assay is assessing its effect on bacterial growth. A standard protocol is a bacterial growth curve assay. An overnight culture of E. coli is diluted into fresh media (e.g., LB) and grown to log-phase. G0507 is added to the culture at varying concentrations (e.g., 0, 1, 10, 50, 100 uM). The optical density at 600 nm (OD₆00) is then measured every 30 minutes over several hours using a plate reader to construct growth curves and determine the concentration for 50% growth inhibition (IC₅0).
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| Animal Protocol |
A specific in vivo animal experimental protocol is not provided. However, as G0507 is a chemical probe to study Gram-negative bacteria, a typical in vivo model could be a murine thigh infection model. In this model, mice are immunosuppressed (with cyclophosphamide) to maintain bacterial load, and then infected intramuscularly with E. coli. G0507 is administered via intraperitoneal (IP) injection. After a certain period (e.g., 24 hours), the mice are euthanized, and the thigh muscle is excised. The bacterial load (CFU) in the tissue homogenate is then quantified.
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| ADME/Pharmacokinetics |
Specific PK data for G0507 is not provided. As a research probe, its properties such as solubility, stability in plasma, and clearance would need to be characterized if it were to be developed further. It is currently a tool for understanding fundamental bacterial physiology, not a clinical candidate.
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| Toxicity/Toxicokinetics |
No specific toxicity information is available. Its potential toxicity would be a concern if it were to be developed as an antibacterial agent. As a research tool, the focus is on its mechanism of action. Standard biological safety protocols should be followed when handling G0507.
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| References |
[1]. Nickerson NN, et al. A Novel Inhibitor of the LolCDE ABC Transporter Essential for Lipoprotein Trafficking in Gram-Negative Bacteria. Antimicrob Agents Chemother. 2018 Mar 27;62(4).
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| Additional Infomation |
LolCDE is an attractive but challenging antibiotic target because it is unique to bacteria and essential for viability. G0507 serves as a tool compound to validate LolCDE as a drug target. The induction of the σE stress response is a specific and measurable consequence of its mechanism, making it an excellent tool for dissecting bacterial cell envelope biology.
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| Molecular Formula |
C18H15N3O3S
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|---|---|
| Molecular Weight |
353.395002603531
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| Exact Mass |
353.083
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| CAS # |
1223998-29-5
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| PubChem CID |
50813566
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
538
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC=C(S1)C2=C(C3=C(N2)NC(=O)NC3=O)C4=CC=C(C=C4)OC
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| InChi Key |
GZLHQRURTUJCHZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H15N3O3S/c1-9-3-8-12(25-9)15-13(10-4-6-11(24-2)7-5-10)14-16(19-15)20-18(23)21-17(14)22/h3-8H,1-2H3,(H3,19,20,21,22,23)
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| Chemical Name |
5-(4-methoxyphenyl)-6-(5-methylthiophen-2-yl)-1,7-dihydropyrrolo[2,3-d]pyrimidine-2,4-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 : 5 mg/mL (14.15 mM)
H2O : < 0.1 mg/mL |
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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 | 2.8297 mL | 14.1483 mL | 28.2965 mL | |
| 5 mM | 0.5659 mL | 2.8297 mL | 5.6593 mL | |
| 10 mM | 0.2830 mL | 1.4148 mL | 2.8297 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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