G907
目录号 : GC39569
G907 是 ABC transporter, MsbA 的选择性小分子拮抗剂。 G907 抑制两栖动物中纯化的大肠杆菌 MsbA (IC50=18 nM)。G907 通过楔入结构上保守的跨膜袋，使 MsbA 陷入向内的脂多糖结合构象中。G907 具有杀菌活性。
Cas No.:2244035-16-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
G907 is a selective small-molecule antagonist of ATP-binding cassette (ABC) transporter, MsbA. It inhibits purified E. coli MsbA in amphipols with an IC50 of 18 nM. G907 traps MsbA in an inward-facing, lipopolysaccharide-bound conformation by wedging into an architecturally conserved transmembrane pocket. Bactericidal activity[1].
[1]. Ho H, et al. Structural basis for dual-mode inhibition of the ABC transporter MsbA. Nature. 2018 May;557(7704):196-201.
| Cas No. | 2244035-16-1 | SDF | |
| Canonical SMILES | O=C(O)/C=C/C1=C(C2CC2)C3=CC(OC(C4=C(C5CC5)C=CC=C4Cl)C)=CC=C3N=C1 | ||
| 分子式 | C26H24ClNO3 | 分子量 | 433.93 |
| 溶解度 | DMSO: 83.33 mg/mL (192.04 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 | 4.609 mL |
| 10 mM | 0.2305 mL | 1.1523 mL | 2.3045 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Structural basis for dual-mode inhibition of the ABC transporter MsbA
Nature 2018 May;557(7704):196-201.PMID:29720648DOI:10.1038/s41586-018-0083-5.
The movement of core-lipopolysaccharide across the inner membrane of Gram-negative bacteria is catalysed by an essential ATP-binding cassette transporter, MsbA. Recent structures of MsbA and related transporters have provided insights into the molecular basis of active lipid transport; however, structural information about their pharmacological modulation remains limited. Here we report the 2.9 Å resolution structure of MsbA in complex with G907, a selective small-molecule antagonist with bactericidal activity, revealing an unprecedented mechanism of ABC transporter inhibition. G907 traps MsbA in an inward-facing, lipopolysaccharide-bound conformation by wedging into an architecturally conserved transmembrane pocket. A second allosteric mechanism of antagonism occurs through structural and functional uncoupling of the nucleotide-binding domains. This study establishes a framework for the selective modulation of ABC transporters and provides rational avenues for the design of new antibiotics and other therapeutics targeting this protein family.
Biosensor for Multimodal Characterization of an Essential ABC Transporter for Next-Generation Antibiotic Research
ACS Appl Mater Interfaces 2023 Mar 15;15(10):12766-12776.PMID:36866935DOI:10.1021/acsami.2c21556.
As the threat of antibiotic resistance increases, there is a particular focus on developing antimicrobials against pathogenic bacteria whose multidrug resistance is especially entrenched and concerning. One such target for novel antimicrobials is the ATP-binding cassette (ABC) transporter MsbA that is present in the plasma membrane of Gram-negative pathogenic bacteria where it is fundamental to the survival of these bacteria. Supported lipid bilayers (SLBs) are useful in monitoring membrane protein structure and function since they can be integrated with a variety of optical, biochemical, and electrochemical techniques. Here, we form SLBs containing Escherichia coli MsbA and use atomic force microscopy (AFM) and structured illumination microscopy (SIM) as high-resolution microscopy techniques to study the integrity of the SLBs and incorporated MsbA proteins. We then integrate these SLBs on microelectrode arrays (MEA) based on the conducting polymer poly(3,4-ethylenedioxy-thiophene) poly(styrene sulfonate) (PEDOT:PSS) using electrochemical impedance spectroscopy (EIS) to monitor ion flow through MsbA proteins in response to ATP hydrolysis. These EIS measurements can be correlated with the biochemical detection of MsbA-ATPase activity. To show the potential of this SLB approach, we observe not only the activity of wild-type MsbA but also the activity of two previously characterized mutants along with quinoline-based MsbA inhibitor G907 to show that EIS systems can detect changes in ABC transporter activity. Our work combines a multitude of techniques to thoroughly investigate MsbA in lipid bilayers as well as the effects of potential inhibitors of this protein. We envisage that this platform will facilitate the development of next-generation antimicrobials that inhibit MsbA or other essential membrane transporters in microorganisms.
Vagal afferent responses to fatty acids of different chain length in the rat
Am J Physiol Gastrointest Liver Physiol 2001 Oct;281(4):G907-15.PMID:11557510DOI:10.1152/ajpgi.2001.281.4.G907.
The role of cholecystokinin (CCK) in the effect of dietary lipid on proximal gastrointestinal function and satiety is controversial. Recent work suggests that fatty acid chain length may be a determining factor. We investigated the mechanism by which long- and short-chain fatty acids activate jejunal afferent nerves in rats. Whole mesenteric afferent nerve discharge was recorded in anaesthetized male Wistar rats during luminal perfusion of saline, sodium oleate, and sodium butyrate (both 10 mM). Both fatty acids evoked characteristic afferent nerve responses, distinct from the mechanical response to saline, that were abolished in rats following chronic subdiaphragmatic vagotomy. The effect of oleate was abolished by the CCK-A receptor antagonist Devazepide (0.5 mg/kg), whereas the effect of butyrate persisted despite pretreatment with either Devazepide or a combination of the calcium channel inhibitors nifedipine (1 mg/kg) and the omega-conotoxins GVIA and SVIB (each 25 microg/kg). In summary, long- and short-chain fatty acids activate intestinal vagal afferents by different mechanisms; oleate acts via a CCK-mediated mechanism and butyrate appears to have a direct effect on afferent terminals.
Pleiotropic effect of LEC mutation: a rodent model of Wilson's disease
Am J Physiol 1994 May;266(5 Pt 1):G907-13.PMID:8203535DOI:10.1152/ajpgi.1994.266.5.G907.
Metabolic studies with 67Cu were undertaken to identify the site of the cellular defect in copper metabolism in the Long-Evans Cinnamon (LEC) rat. The apparent rate of copper uptake by LEC primary hepatocytes was increased [maximal velocity (Vmax) = 259 pmol.min-1.mg protein-1] compared with controls (Vmax = 161 pmol.min-1.mg protein-1); however, Michaelis-Menten constant (Km) values were comparable (11.8 and 12.7 microM, LEC and control, respectively). Efflux of copper from LEC and control hepatocytes was similar from 0 to 15 min, but was reduced from 15 to 60 min in the former. Although hepatic copper contents were markedly elevated in LEC rats compared with controls (658 +/- 199 vs. 21.5 +/- 6.6 micrograms/g dry wt), biliary copper concentration was reduced in LEC rats compared with controls (0.187 vs. 1.39 +/- 0.66 microgram/ml). Subcellular fractionation of LEC liver homogenates revealed approximately 75% of copper to be present in cytosol, with gradients of copper concentration from cytosol to either lysosome or microsomal subcellular fractions. LEC rat bile and hepatic microsome and lysosome fractions contained smaller fractions of 67Cu administered intravenously as cupric acetate compared with control rats. However, recovery of 67Cu in bile and in lysosomal subcellular fractions were similar for LEC and controls following administration of 67Cu-labeled asialoceruloplasmin, which is targeted to lysosomes. This discordance suggests a possible defect in the entry of copper into lysosomes but normal delivery of lysosomal copper to bile. Based on these findings, we conclude that the mutation in LEC rats alters copper transport at more than one cellular site.
Superoxide anion generation by in situ perfused rat liver: effect of in vivo endotoxin
Am J Physiol 1990 Dec;259(6 Pt 1):G907-12.PMID:2175553DOI:10.1152/ajpgi.1990.259.6.G907.
A simple method is described to monitor the superoxide dismutase (SOD)-inhibitable production of superoxide anion (O2-.) in the liver. The isolated rat liver was perfused in situ with ferricytochrome c, and the reduction of this substrate during perfusion was determined. Within 30 s after the introduction of the substrate, significant reduction of ferricytochrome c was observed and stabilized at 2-4 min. A marked reduction of the substrate was observed in the livers of rats that received Escherichia coli lipopolysaccharide (LPS, 1 mg/kg) in vivo 3 h before liver perfusion. Ferricytochrome c reduction was inhibited by SOD, but not significantly with allopurinol or deferoxamine mesylate in the livers of LPS-treated rats. Control livers exhibited only a small reduction of the substrate, and this was not significantly inhibited by SOD. After in vivo LPS administration, O2-. production peaked in the liver at 3 h (6.6 nmol/min) and returned toward normal at 6 h (1 nmol/min) after endotoxin. The amount of O2-. generated by the endotoxic livers was dose related. At 3 h post-LPS, neutrophil infiltration and necrotic areas were found in the histological sections of the liver with concomitant elevation of serum aminotransferases, indicating hepatic abnormalities during the early stage of endotoxemia. Phorbol myristate acetate in the perfusion system markedly enhanced O2-. generation in the endotoxic liver. These results show that the perfused rat liver can be used to measure O2-. generation following in vivo stimuli. The data also demonstrate that O2-. release after LPS treatment in vivo is a short and early event and may have an important role in hepatic injury in endotoxemic conditions.