LIFR/GPBAR1 modulator 1
LIFR/GPBAR1 modulator 1 is an orally active, potent GPBAR1 agonist (EC50 = 0.2 μM) and LIFR inhibitor (IC50 = 7.9 μM). LIFR/GPBAR1 modulator 1 upregulates leukaemia inhibitory factor (LIF)-mediated mRNA expression of LIFR and GPBAR1 and significantly reduces the expression of pro-fibrosis markers (COL1A1, ASMA, and TGFβ), and reduces TIMP1 expression and increases MMP9 expression. LIFR/GPBAR1 modulator 1 can be used for the study of human fibrotic disorders.
For research use only. We do not sell to patients.
- Formula: C32H31NO2
- Molecular Weight:461.59
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
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MMP9 |
In Vitro
LIFR/GPBAR1 modulator 1 (Compound 2o) (0.1-50 μM) shows an inhibitory efficiency of 89.6 % on LIFR at a concentration of 10 μM in HepG2 cells (IC50 = 7.9 μM). In HEK293T cells, it shows an activation efficiency of 79.4 % on GPBAR1 at 10 μM (EC50 = 0.2 μM)[1].
LIFR/GPBAR1 modulator 1 (1–10 μM, 24 h) regulates the expression of fibrosis-related genes in a concentration-dependent manner, in leukaemia inhibitory factor (LIF)-mediated human hepatic stellate cells (HSC) LX2. At a concentration of 10 μM, it upregulates the mRNA expression of LIFR and GPBAR1 and significantly reduces the expression of pro-fibrosis markers (COL1A1, ASMA, and TGFβ). Simultaneously, it reduces TIMP1 expression and increases MMP9 expression, indicating that it promotes ECM degradation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:Leukaemia inhibitory factor (LIF)-mediated human HSC LX2
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Concentration:1 μM, 5 μM, 10 μM
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Incubation Time:24 h
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Result:Upregulated the mRNA expression of LIFR and GPBAR1 and significantly reduced the expression of pro-fibrosis markers (COL1A1, ASMA, and TGFβ).
Reduced TIMP1 expression and increased MMP9 expression.
Parmacokinetics
| Species | Dose | Route | T1/2 | Cmax | Tmax | AUC0-t |
|---|---|---|---|---|---|---|
| Mice | 10 mg/kg | p.o. | 1.6 h | 37.63 ng/mL | 1 h | 113.69 ng·h/mL |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Liver fibrosis was induced by intraperitoneal (i.p.) administration of carbon tetrachloride (CCl4) at a dose of 500 μL/kg, dissolved in an equal volume of olive oil, and administered twice per week for 1 week to Male C57BL/6J mice[1].
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Dosage:10 mg/kg
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Administration:P.o., once daily for 7 days
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Result:Reduced weight loss.
Significantly reduced plasma levels of AST, ALT, bilirubin, and LDH.
Reduced CCl4-induced white blood cell (WBC) count elevation and modulated the percentages of neutrophils, lymphocytes, and monocytes.
Improved hepatocellular necrosis and inflammatory infiltration and significantly reduced collagen deposition and fibrosis area.
Significantly downregulated the mRNA expression of fibrosis marker genes (Colla1, aSma, Tgβ) in liver tissue.
Chemical Information
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Molecular Weight 461.59
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Formula C32H31NO2
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SMILES
CC1=CC=C(C#N)C=C1C2=CC=C([C@@H]3C([C@]4([H])[C@@](CCC5=O)([H])[C@]5(C)C3)=C(CC6)C(CC4)=CC6=O)C=C2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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RT-PCR
Reverse transcription technology uses RNA as a template to synthesize DNA. RT-PCR is simple, specific and sensitive, and can be used to detect gene expression levels and expression differences in cells; detect RNA virus content; clone cDNA sequences of specific genes.
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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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Real Time qPCR (Q-PCR)
Real-time quantitative PCR (qPCR) quantifies an amplifiable nucleic-acid target by monitoring fluorescence during PCR cycling rather than measuring product only after amplification. The increase in fluorescence tracks accumulation of PCR product, and the quantification cycle (Cq; historically also Ct/CP) is related to the initial amount of target: samples containing more starting target generally reach the defined fluorescence threshold in fewer cycles.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)