OP-1118
OP-1118 (Fidaxomicin metabolite OP-1118) is an orally active dual inhibitor of NF-κB and ERK1/2, with low systemic plasma exposure, no accumulation, and primary excretion via feces. By inhibiting the phosphorylation of NF-κB and ERK1/2 and reducing the expression of pro-inflammatory cytokines, OP-1118 exerts significant anti-inflammatory, cytoprotective, anti-apoptotic and antibacterial activities. In Clostridium difficile infection models, OP-1118 effectively blocks toxin-mediated intestinal inflammation, cell rounding, histological damage and apoptosis, and its protective effect can be reversed by PMA (HY-18739).
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- CAS No.: 1030825-28-5
- Formule: C48H68Cl2O17
- Masse moléculaire:987.95
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
IC50 & Target
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ERK1 |
ERK2 |
In Vitro
OP-1118 (60-120 μM; 30 min pre-treatment plus 4 h exposure) dose-dependently inhibits the expression of proinflammatory cytokines and the phosphorylation of NF-κB mediated by C. difficile toxin A and toxin B, as well as histological damage in fresh human colonic explants[1].
OP-1118 (120 μM; 30 min pre-treatment followed by 4 h/1 h treatment) blocks TNF-α expression and NF-κB phosphorylation induced by C. difficile toxin A in RAW264.7 murine macrophages, and this effect is reversed by the NF-κB activator PMA (HY-18739)[1].
OP-1118 (120 μM; 30 min pre-treatment followed by 8 h exposure) inhibits apoptosis induced by C. difficile toxin A and toxin B in human colonic epithelial NCM460 cells, and this effect is reversed by the NF-κB activator PMA (HY-18739)[1].
OP-1118 exhibits an MIC range of 0.25 to 2 μg/mL against C. difficile[1].
OP-1118 (120 μM; 30 min pre-treatment plus 6 h incubation) protects human colonic CCD-18Co fibroblasts against Clostridioides difficile toxin A-mediated cell rounding[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NCM460 human colonic epithelial cells
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Concentration:120 μM
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Incubation Time:30 min pretreatment followed by 8 h toxin A or B exposure
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Result:Significantly reduced toxin A- and B-mediated apoptosis in NCM460 cells, as detected by TUNEL assay.
Lost antiapoptotic effect on toxin-exposed NCM460 cells when cells were pretreated with PMA.
In Vivo
OP-1118 is generated via oral administration of Fidaxomicin (HY-17580). The combined peak concentrations of Fidaxomicin (30-75 mg/kg; p.o.; single dose) and OP-1118 can reach up to 920 μg/g and 1,600 μg/g, respectively[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (10-week-old male)[2]
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Dosage:60 μM; 120 μM
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Administration:Intra-ileal loop injection; single dose; 30 minutes prior to toxin A
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Result:Reduced mean histology score at 120 μM.
Reduced toxin A-induced ileal IL-1β protein expression and IL-1β mRNA expression at 120 μM.
Diminished toxin A-induced ERK1/2 phosphorylation in ileal mucosal tissues at 120 μM.
Failed to produce statistically significant reductions in toxin A-mediated histologic damage, IL-1β protein, or IL-1β mRNA expression at 60 μM.
Reduced basal ileal IL-1β protein expression in sham control mice at 120 μM.
Chemical Information
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CAS No. 1030825-28-5
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Masse moléculaire 987.95
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Formule C48H68Cl2O17
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SMILES
O=C(C(C(O)=C1Cl)=C(C(Cl)=C1O)CC)O[C@@H]([C@@H](O[C@@H]2OC/C(C(O[C@](C/C=C(/C=C([C@@H]3O[C@H](OC4(C)C)[C@H]([C@H]([C@@H]4O)O)O)\C)C)([H])[C@H](O)C)=O)=C\C=C\C[C@@H](/C(C)=C/[C@@H]3CC)O)C)[C@H]([C@H]2OC)O
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Synonyms
Fidaxomicin metabolite OP-1118
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Koon HW, et al. Fidaxomicin and OP-1118 Inhibit Clostridium difficile Toxin A- and B-Mediated Inflammatory Responses via Inhibition of NF-κB Activity. Antimicrob Agents Chemother. 2017;62(1):e01513-17. Published 2017 Dec 21. [Content Brief]
[2]. Koon HW, et al. Fidaxomicin inhibits Clostridium difficile toxin A-mediated enteritis in the mouse ileum. Antimicrob Agents Chemother. 2014;58(8):4642-4650. [Content Brief]
[4]. Deshpande A, et al. Effect of Fidaxomicin versus Vancomycin on Susceptibility to Intestinal Colonization with Vancomycin-Resistant Enterococci and Klebsiella pneumoniae in Mice. Antimicrob Agents Chemother. 2016;60(7):3988-3993. Published 2016 Jun 20. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
OP-1118 Related Classifications
HY-138135 Related Classifications
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Keywords
- OP-1118
- 1030825-28-5
- Fidaxomicin metabolite OP-1118
- OP1118
- OP 1118
- Fidaxomicin metabolite OP1118
- Fidaxomicin metabolite OP 1118
- NF-κB
- ERK
- Apoptosis
- Bacterial
- male C57BL/6 mice
- proinflammatory cytokine
- ERK1/2
- Clostridioides difficile infection
- Clostridium difficile
- NCM460 human colonic epithelial cells
- RAW264.7 mouse macrophages
- TNF-α
- human colonic CCD-18Co fibroblasts
- Inhibitor
- inhibitor
- inhibit