Antifibrotic agent 1
Antifibrotic agent 1 is an orally active anti-idiopathic pulmonary fibrosis (IPF) agent. Antifibrotic agent 1 effectively attenuates IPF-related processes, including TGF-β induced EMT and FMT processes, as well as pro-fibrotic M2 polarization. Antifibrotic agent 1 selectively inhibits CSF-1R, PDGFR-α and Src family kinases (SFKs), while sparing VEGFRs, FGFRs and Abl to minimize off-target toxicity. Antifibrotic agent 1 has potent anti-fibrotic activity in Bleomycin (BLM) (HY-108345)-induced pulmonary fibrosis mice model.
For research use only. We do not sell to patients.
- Formula: C27H23ClN6O2
- Molecular Weight:498.96
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
PDGFRα |
Collagen I 40.5 nM (IC50) |
Fyn |
Hck |
Lyn |
Lck |
Yes |
In Vitro
Antifibrotic agent 1 (Compound 22) (0.001-10 μM, 48 h,) exhibits profound anti-fibrotic activity, suppressing COL1A1 expression by 95.0% at 1 μM, with an IC50 of 40.5 nM in A549 cells[1].
Antifibrotic agent 1 (1-200 μM) exhibits anti-fibrotic effects with low cytotoxicity across A549, HEK293 and L02 cells (CC50 > 200μM)[1].
Antifibrotic agent 1 (0.1-10 μM, 48 h) dose-dependently reduces the protein level of COL1A1, inhibiting IPF-related EMT and FMT processes in TGF-β-stimulated A549, HFL1 and HLFs cells[1].
Antifibrotic agent 1 (1-10 μM, 48 h) selectively inhibits the bone marrow-derived macrophages (BMDM) polarization towards the pro-fibrotic M2 phenotype at a concentration of 10 μM[1].
Antifibrotic agent 1 (1-100 nM) selectively inhibits CSF-1R, PDGFR-α and SFKs to mitigate IPF progression, while sparing VEGFRs, FGFRs and Abl to minimize off-target toxicity[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:A549 cells, HFL1 cells, HLFs cells
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Concentration:0.1, 0.5, 1, 10 μM
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Incubation Time:48 h after TGF-β stimulated 48 h
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Result:Dose-dependently reduced the protein level of COL1A1 in IPF-related EMT and FMT models and primary human lung fibroblasts model.
Parmacokinetics
| Species | Dose | Route | T1/2 | AUC | MRT | Clearance (CL) | Vd | Tmax | Plasma Concentration | Bioavailability |
|---|---|---|---|---|---|---|---|---|---|---|
| Mice | 2 mg/kg | i.v. | 2.37 h | 437 ng·h/mL | 0.4 h | 79.8 mL/min/kg | 1.802 L/kg | / | / | / |
| Mice | 5 mg/kg | p.o. | 3.15 h | / | 2.32 h | / | / | 0.42 h | 137 ng·h/mL | 12.6 % |
In Vivo
Antifibrotic agent 1 (60 mg/kg, p.o., daily for 10 days) has superior anti-fibrotic efficacy, significantly alleviating lung fibrosis, reducing inflammation and pro-fibrotic M2-associated cytokine levels, and improving lung function in BLM-induced pulmonary fibrosis mice model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male C57BL/6 mice (8 weeks old) were given an intratracheal administration of BLM (1.8 mg/kg) to induce pulmonary fibrosis[1].
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Dosage:30, 60 mg/kg
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Administration:Oral gavage (p.o.), daily for 14 days and then measured body and lung tissues weight as well as collected lung tissues.
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Result:Significantly alleviated weight losses, increased survival rate and improved lung functions with increased lung coefficient value in mice mode.
Notably downregulated Tgf-β mRNA, reduced both the mRNA and protein levels of Fn1 and Col1a1, and decreased hydroxyproline content in the lung tissues in mice model at the dose of 60 mg/kg.
Significantly reduced Tnf and Ccl2 mRNA levels but increased IL-10 mRNA level, modulating inflammation to further alleviate pulmonary fibrosis in mice model.
Strongly downregulated M2-associated genes (Arg1, Mrc1) but not the M1 marker CD86, selectively inhibiting M2 macrophage polarization without significantly affecting M1 polarization in mice model.
Potently alleviated pathological changes related lung fibrosis and decreased collagen fibers with a 54.6 % reduction in fibrosis area in mice model at the dose of 60 mg/kg.
Chemical Information
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Molecular Weight 498.96
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Formula C27H23ClN6O2
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SMILES
CC(NC1=CC=C(C(Cl)=C1)NC(C2=CC=C(C(C#CC3=CC(C4=CN(N=C4)C)=CN=C3N)=C2)C)=O)=O
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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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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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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
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Antifibrotic agent 1 Related Classifications
HY-176194 Related Classifications
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