OP-1118  (Synonyms: Fidaxomicin metabolite 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)^[1][2][3].

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.

OP-1118 (6120 μM; intraluminal injection into ileal loops; administered 30 min in advance) significantly inhibits C. difficile toxin A-mediated ileal histological damage, IL-1β expression, and ERK1/2 phosphorylation in male C57BL/6 mice^[2].
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.

987.95

C₄₈H₆₈Cl₂O₁₇

1030825-28-5

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Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [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]

  [3]. Guery B, et al. Pharmacokinetic analysis of an extended-pulsed fidaxomicin regimen for the treatment of Clostridioides (Clostridium) difficile infection in patients aged 60 years and older in the EXTEND randomized controlled trial[J]. Journal of Antimicrobial Chemotherapy, 2020, 75(4): 1014-1018.

  [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]