PXS 64
PXS 64, a mannose-6-phosphate (M6P) analogue. a lipophilic prodrug of PXS 25 (HY-181430). PXS 64 is an effective anti-fibrotic agent by inhibiting the activation of latent TGF-β1. PXS64, inhibits fibrosis via TGF-β1 pathway in human lung fibroblasts. PXS 64 reduces TGFβ-mediated collagen IV, fibronectin, MCP-1, and phospho-smad2 expression in kidney cells. PXS 64 reduces collagen deposition in dermal scar fibroblasts. PXS 64 can be used for the research of chronic kidney disease, idiopathic pulmonary fibrosis, scarring.
For research use only. We do not sell to patients.
- CAS No.: 1253691-50-7
- Formula: C27H43O12P
- Molecular Weight:590.60
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
In Vitro
PXS 64 (10 µM; 48 h) inhibits latent TGF-β1 activation, suppresses pro-fibrotic and pro-inflammatory marker expression, and selectively reduces TGF-β1-induced pSmad2 expression without affecting pAKT or pERK. PXS64 alone has no effect on\nfibronectin, collagen IV and MCP-1mRNA and protein expression[1].
PXS64 (1-10 µM; 24.5 h) demonstrates a significant inhibition of fibrotic markers ( fibronectin and collagen) in rhTGF-β1 stimulated NHLFs[2].
PXS64 (10 µM; 24 h) presents an improved phenotype in terms of their morphological appearance, as well as a decrease in fibrotic markers (collagen, CTGF, TGF-β3, tenascin C, αSMA and THBS1) in fibroblasts[2].
PXS64 exhibits a very potent anti-fibrotic activity (as measured by the inhibition of αSMA, fibronectin and collagen) in HF19 cells[2].
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:NHLFs
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Concentration:1 µM, 3 µM, 10 µM
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Incubation Time:24.5 h
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Result:At10 μM, supressed fibronectin expression by 53% and of collagen by 86%.
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Cell Line:fibroblasts
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Concentration:10 µM
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Incubation Time:24 h
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Result:Down-regulated a number of fibrotic associated genes, such as collagen, connective tissue growth factor (CTGF), TGF-β3, tenascin C, αSMA and thrombospondin 1 (THBS1).
Changed from a senescent, growth-arrested state (as expected to be seen in fibroblasts) to a regular fusiform, healthy phenotype.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 mice (male, 6-8 weeks old, weighing 20-25 g, unilateral ureteral obstruction model)[1]
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Dosage:10 μM
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Administration:i.p.; daily; 7 days
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Result:Reduced the tubulointerstitial fibrosis index from 3.2 to 2.5, decreased fibronectin mRNA from 12-fold to 1.8-fold and collagen IV mRNA from 9.6-fold to 2.1-fold expression, lowered fibronectin protein from 314.6% to 71.9% and collagen content from 0.69 μg/mg to 0.4 μg/mg, reduced MCP-1 mRNA expression, decreased CD45-positive cell accumulation from 6.7%/area to 1.1%/area and F4/80-positive cell infiltration from 11.3%/area to 7.9%/area, suppressed active TGF-β1 levels from 599.4 pg/mL to 55 pg/mL, and reduced phosphorylated Smad2 protein expression by 80%.
Chemical Information
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CAS No. 1253691-50-7
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Molecular Weight 590.60
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Formula C27H43O12P
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SMILES
CC(C)(C)C(OCOP(CC[C@H]([C@H]([C@@H]([C@@H]1O)O)O)O[C@@H]1OC2=C(C=C(C=C2)C)C)(OCOC(C(C)(C)C)=O)=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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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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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
[1]. Zhang J, et al. A cationic-independent mannose 6-phosphate receptor inhibitor (PXS64) ameliorates kidney fibrosis by inhibiting activation of transforming growth factor-β1. PLoS One. 2015;10(2):e0116888. Published 2015 Feb 6. [Content Brief]
[2]. Schilter H, et al. The mannose-6-phosphate analogue, PXS64, inhibits fibrosis via TGF-β1 pathway in human lung fibroblasts. Immunol Lett. 2015;165(2):90-101. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)