| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
MsbA (ATP-binding cassette transporter). G907 is a selective antagonist of MsbA, an essential ABC transporter that flips lipopolysaccharide (LPS) across the inner membrane of Gram-negative bacteria. By trapping MsbA in an inward-facing LPS-bound conformation, G907 inhibits LPS transport and exerts bactericidal activity.
|
|---|---|
| ln Vitro |
G907 (0.1 nM-100 μM) completely suppresses Escherichia coli MsbA activity, with an IC50 value of 18 nM[1]. G907 has MsbA-blocking allosteric inhibition action [1]. WT pontics biotin-PE transport activity [2].
G907 inhibits E. coli MsbA with an IC₅0 of 18 nM. The compound is a quinoline-based selective small-molecule antagonist that traps MsbA in an inward-facing, LPS-bound conformation. It exerts bactericidal activity against Gram-negative bacteria by disrupting LPS transport and outer membrane integrity. |
| ln Vivo |
G907 is expected to demonstrate in vivo efficacy in mouse models of Gram-negative bacterial infection. By inhibiting MsbA, the compound disrupts LPS transport and bacterial outer membrane integrity, leading to bacterial death. Efficacy would be assessed in sepsis or localized infection models, with bacterial burden and survival as endpoints.
|
| Enzyme Assay |
MsbA ATPase activity is measured using a malachite green or coupled enzyme assay. MsbA protein (reconstituted in liposomes or amphipols) is incubated with ATP and serial dilutions of test compound. Phosphate release (from ATP hydrolysis) is quantified colorimetrically. LPS transport assays measure the flipping of fluorescently labeled LPS across membranes. IC₅0 values are calculated from ATPase inhibition.
|
| Cell Assay |
Gram-negative bacterial strains (e.g., E. coli, Pseudomonas aeruginosa) are treated with G907 at various concentrations. Bacterial growth is monitored by OD₆00 measurements. Minimum inhibitory concentration (MIC) is determined by broth microdilution according to CLSI guidelines. Bactericidal activity is assessed by time-kill assays. Membrane integrity is evaluated by propidium iodide uptake.
|
| Animal Protocol |
Mouse models of Gram-negative infection (e.g., E. coli peritonitis or pneumonia models) are treated with G907 via intraperitoneal or intravenous injection. Bacterial burden in blood, peritoneal fluid, or lungs is quantified. Survival is monitored. Pharmacodynamic markers (LPS release, inflammatory cytokines) are measured.
|
| ADME/Pharmacokinetics |
G907 has a molecular weight of 433.93 g/mol and formula C2₆H24ClNO3. Standard PK parameters (half-life, Cmax, AUC, clearance, volume of distribution) would be determined in rodent studies. The compound is formulated in suitable vehicles containing DMSO and co-solvents for in vivo administration.
|
| Toxicity/Toxicokinetics |
Toxicology data for G907 are not publicly available. As an antibacterial targeting a bacterial protein, the compound would be evaluated for selectivity against mammalian ABC transporters. Standard preclinical safety assessment would include cytotoxicity assays, hERG testing, and repeat-dose toxicology studies in rodents.
|
| References |
[1]. Ho H, et al. Structural basis for dual-mode inhibition of the ABC transporter MsbA. Nature. 2018 May;557(7704):196-201.
[2]. Guo D, et al. Energetics of lipid transport by the ABC transporter MsbA is lipid dependent. Commun Biol. 2021 Dec 9;4(1):1379. |
| Additional Infomation |
G907 is a research compound for studying bacterial ABC transporters and developing novel antibiotics targeting Gram-negative bacteria. It is not clinically approved. The compound's unique mechanism of trapping MsbA in an inward-facing conformation provides a valuable tool for understanding LPS transport and for developing antibiotics against multidrug-resistant Gram-negative pathogens.
|
| Molecular Formula |
C26H24CLNO3
|
|---|---|
| Molecular Weight |
433.926666259766
|
| Exact Mass |
433.144
|
| CAS # |
2244035-16-1
|
| PubChem CID |
139035046
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
6.5
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
31
|
| Complexity |
676
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C1=C(C=CC=C1Cl)C2CC2)OC3=CC4=C(C(=CN=C4C=C3)/C=C/C(=O)O)C5CC5
|
| InChi Key |
HOMQCLNBKVHZGD-FMIVXFBMSA-N
|
| InChi Code |
InChI=1S/C26H24ClNO3/c1-15(25-20(16-5-6-16)3-2-4-22(25)27)31-19-10-11-23-21(13-19)26(17-7-8-17)18(14-28-23)9-12-24(29)30/h2-4,9-17H,5-8H2,1H3,(H,29,30)/b12-9+
|
| Chemical Name |
(E)-3-[6-[1-(2-chloro-6-cyclopropylphenyl)ethoxy]-4-cyclopropylquinolin-3-yl]prop-2-enoic acid
|
| 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) |
DMSO : ~83.33 mg/mL (~192.04 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3045 mL | 11.5226 mL | 23.0452 mL | |
| 5 mM | 0.4609 mL | 2.3045 mL | 4.6090 mL | |
| 10 mM | 0.2305 mL | 1.1523 mL | 2.3045 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
