FXR agonist 18
FXR agonist 18 is an orally active FXR agonist, with an EC50 of 10 nM against human FXR and an EC50 of 1360 nM against human TGR5. FXR agonist 18 inhibits inflammatory responses by reducing nitrite production, downregulating the expression of pro-inflammatory genes (Tnf, Adgre1, Cyp8b1, upregulating the expression of FXR, Hmox1, Nqo1, Nrf2, and enhancing antioxidant responses. FXR agonist 18 ameliorates liver fibrosis in mice, exhibits protective effects in mice with cholestatic liver injury, and shows anti-MASH efficacy. FXR agonist 18 can be used in studies of metabolic dysfunction-associated steatohepatitis.
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- CAS. Nr.: 3061938-00-6
- Formel: C27H44N2O3S
- Molecular Weight:476.71
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
NQO1 |
In Vitro
FXR agonist 18 (Compound 27) potently activates FXR-mediated transcription in HEK-293 cells, with an EC50 of 128 nM[1].
FXR agonist 18 acts as a partial agonist of human MRGPRX4, with an EC50 value of 25,685 nM[1].
FXR agonist 18 (20 μM; 1 h pretreatment, 24 h LPS stimulation) inhibits LPS (HY-D1056)-induced inflammatory responses in RAW264.7 macrophages by reducing nitrite production, downregulating the expression of pro-inflammatory genes (Tnf, Adgre1, Cyp8b1), upregulating the expression of FXR, Hmox1, Nqo1, and Nrf2, and enhancing antioxidant responses[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
In Vivo
FXR agonist 18 (20 mg/kg; p.o.; once daily; for 5 consecutive days) exerts significant protective effects in mice with ANIT (HY-W540630)-induced cholestatic liver injury by normalizing serum biomarkers and alleviating hepatocellular damage[1].
At a dose of 20 mg/kg, FXR agonist 18 (10-20 mg/kg; p.o.; daily; 4 weeks) improves histopathological, fibrotic and serum biomarker parameters in a metabolic dysfunction-associated steatohepatitis (MASH) model induced by the combination of Western diet (WD) and CCl4; the 10 mg/kg dose also exhibits significant anti-MASH efficacy[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (8-week-old male, CCl4-induced liver fibrosis)[1]
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Dosage:30 mg/kg
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Administration:p.o.; daily; 4 weeks
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Result:Markedly attenuated fibrotic pathology, including thinner collagen septa with reduced bridging architecture in portal regions.
Significantly reduced collagen deposition confirmed by Sirius red quantification.
Significantly reduced total liver collagen content compared to the OCA group.
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Animal Model:C57BL/6J (8-week-old male, ANIT-induced cholestatic liver injury)[1]
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Dosage:20 mg/kg
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Administration:p.o.; daily; 5 days
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Result:Effectively normalized all measured serum biomarkers (ALT, AST, ALP, TBA, TBIL) to levels comparable to normal controls.
Showed near-normal liver histology with minimal necrosis or inflammation.
Significantly reduced histopathological injury scores compared to the ANIT model group.
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Animal Model:C57BL/6J (8-week-old male, WD- and CCl4-coinduced metabolic dysfunction-associated steatohepatitis)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:p.o.; daily; 4 weeks
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Result:At 20 mg/kg: Significantly reduced inguinal and epididymal adipose tissue-to-body weight ratios to normal levels.
Achieved more pronounced reduction in hepatic lipid accumulation than OCA.
Significantly improved hepatocyte ballooning (surpassing OCA efficacy).
Achieved >50% reduction in fibrotic collagen area ratio (greater than OCA's 30% reduction).
Markedly ameliorated mitochondrial ultrastructural injuries.
Showed the most substantial improvements in serum biomarkers (ALT, AST, TBA, TC, HDL, LDL) compared to OCA.
At 10 mg/kg: Ameliorated hepatic steatosis and lobular inflammation.
Attenuated liver fibrosis.
Chemical Information
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CAS. Nr. 3061938-00-6
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Molecular Weight 476.71
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Formel C27H44N2O3S
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SMILES
[H][C@@]12C[C@@H](CC[C@@]1([C@]3(CC[C@@]4([C@H](CC[C@]4([C@@]3([C@@H]([C@@H]2CC)O)[H])[H])[C@@H](CCC5=NNC(O5)=S)C)C)[H])C)O
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Protokoll
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Fibrosis/Collagen Morphometry
Fibrosis and collagen morphometry is based on the quantitative visualization of fibrillar collagen deposition in tissue sections using histochemical stains such as Sirius Red (Picrosirius Red) or Masson's trichrome, followed by image-based or polarization-enhanced analysis to estimate collagen proportional area as a surrogate of extracellular matrix accumulation during fibrotic remodeling. Sirius Red combined with polarized light microscopy enhances detection of collagen fibers due to birefringence properties, enabling more specific visualization of collagen type I and III fibrils compared to conventional bright-field histology, while whole-section or region-restricted digital morphometry reduces field-selection bias in fibrosis assessment. Alternative quantitative approaches include second harmonic generation (SHG) and two-photon excited fluorescence microscopy, which enable label-free detection of fibrillar collagen and have been validated against histological staining and biochemica
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Collagen: Sirius Red Staining
Sirius Red or picrosirius red staining is a histochemical method for visualizing collagen-rich extracellular matrix in tissue sections, and collagen fibers are detected as red-stained structures under bright-field microscopy with enhanced birefringence under polarized light. Picrosirius red is useful for assessing total collagen organization, distribution, and fibrosis burden, but polarized color should not be interpreted as a definitive collagen type I versus type III readout because color is affected by fiber orientation, thickness, and packing.
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Connective Tissue: Masson's Trichrome/Collagen Trichrome Staining
Masson’s Trichrome (collagen/trichrome staining) is a histological technique that differentially stains tissue compartments using sequential acidic dyes to distinguish collagen from muscle and cytoplasmic components based on dye affinity and tissue permeability differences, enabling visualization of fibrosis and connective tissue architecture in histological sections. The classical formulation typically uses Weigert's iron hematoxylin for nuclear staining, Biebrich scarlet-acid fuchsin for cytoplasm and muscle, and aniline blue (or light green variants) for collagen, producing a characteristic blue/green collagen signal contrasted against red cytoplasm and dark nuclei. The staining principle relies on selective displacement of smaller dye molecules by larger anionic dyes in collagen-rich regions under controlled acidified conditions, which enhances collagen-specific dye retention. This property makes the method widely used for fibrosis assessment in organs such as heart, liver, lung, a
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Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
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Liver Histomorphometry
Liver histomorphometry is a quantitative histological approach used to measure structural alterations in hepatic tissue, including parenchymal loss, steatosis, fibrosis, and vascular remodeling, by combining stained tissue section analysis with stereological or computerized image-based measurements. Classical morphometric frameworks quantify volume fractions of liver compartments and fibrotic regions using systematic sampling and image analysis, enabling objective comparison of pathological changes across experimental groups. These approaches are widely applied in liver cirrhosis and fibrosis studies to reduce subjectivity in histological scoring and improve reproducibility of tissue evaluation. Recent methodological advances integrate automated image analysis and radiomics-based extraction of histological features from standard liver stains (e. g. , H&E and fibrotic stains), enabling quantitative correlation between morphometric features and fibrosis stages in non-alcoholic fatty live
Reinheit & Dokumentation
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Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)