| 产品描述： | 抗感染抑制剂;Anti-infection Inhibitors;;InformationMAC-545496 MAC-545496 is a nanomolar glycopeptide-resistance-associated protein R(GraR) inhibitor with strong binding affinity to the full-length GraR protein (Kd ≤ 0.1 nM). MAC-545496 can reverse β-lactam resistance in methicillin-resistant strains and synergize with CAMPs. MAC-545496 shows remarkable activity in macrophages and attenuates S. aureus virulence in a G. mellonella larvae infection model.TargetsGraR (Cell-free assay) 0.1 nM(Kd)In vitroMAC-545496 shows inhibition of mprF expression in a concentration-dependent manner; the half-maximal inhibitory concentration (IC50) is 0.0376\u2009µg/mL—matching with the concentration range of the synergistic effect with cefuroxime. MAC-545496 only inhibits the citrate-induced biofilm formation in the wild type in a concentration-dependent manner, suggesting additional potential as a lead for drug discovery. Treatment of S. aureus-infected macrophages with different doses of MAC-545496 added 30\u2009min after phagocytosis shows that the MAC-545496 halts S. aureus replication within macrophages starting at 0.5\u2009µg/mL..In vivoMAC-545496 activity is evidenced by increased survival of the drug-treated larvae as compared to infected untreated ones. This corresponds to concentration-dependent killing of S. aureus in the hemolymph of the larvae observed from the CFUs recovered from the hemolymph 200\u2009min after infection. This matchs with the attenuated virulence of the graR::Tn mutant relative to the wild type in Galleria. Treatment with MAC-545496 recapitulates the phenotype of ΔgraR and ΔgraS mutants, effectively inhibiting intracellular S. aureus growth..Cell Research(from reference)Cell lines：RAW macrophages Concentrations：20\u2009µg/mL Incubation Time：12 h |
| 靶点： |
Glycopeptide-resistance-associated protein R (GraR) |
| 体内研究： |
In vivo, MAC-545496 is effective as a monotherapy for MRSA infected Galleria mellonella larvae. MAC-545496 activity is evidenced by increased survival of the drug-treated larvae as compared to infected untreated ones. This corresponded to concentration-dependent killing of S. aureus in the hemolymph of the larvae observed from the CFUs recovered from the hemolymph 200 min after infection. Treatment of S. aureus-infected larvae with MAC-545496 occurred 30min after infection that mimics acquiring bacterial infection before initiating antimicrobial therapy . |
| 参考文献： |
1. El-Halfawy OM, et al. Discovery of an antivirulence compound that reverses β-lactam resistance in MRSA. Nat Chem Biol. 2019 Nov 25. |
| 保存条件： |
-80℃（运输条件：冰袋低温运输） |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.382 ml |
11.908 ml |
23.816 ml |
| 5 mM |
0.476 ml |
2.382 ml |
4.763 ml |
| 10 mM |
0.238 ml |
1.191 ml |
2.382 ml |
| 50 mM |
0.048 ml |
0.238 ml |
0.476 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京