LT-1339-553
LT-1339-553 is a selective, orally active RIPK1 inhibitor with IC50 values of 4.32, 95.74 and 84.33 nM against RIPK1, RIPK2 and RIPK3, respectively. LT-1339-553 exerts anti-necroptotic activity by inhibiting the AKT/PI3K/NF-κB pathway and the IL-17 pathway. LT-1339-553 reduces liver injury, inflammatory responses and collagen deposition. LT-1339-553 can be used in studies related to schistosomiasis-induced liver fibrosis.
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- CAS. Nr.: 3078683-57-2
- Formel: C21H13F5N4O3
- Molecular Weight:464.34
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
RIPK1 4.32 nM (IC50) |
RIPK2 95.74 nM (IC50) |
RIPK3 84.33 nM (IC50) |
IL-17 |
In Vitro
LT-1339-553 potently protects human HT29 cells from necroptosis induced by TNFα/Smac-mimetic/z-VAD-FMK (HY-16658B) (TSZ), with an EC50 of 14.43 nM; meanwhile, this compound exhibits cytotoxicity at high concentrations, with an IC50 of 1760 nM[1].
LT-1339-553 potently protects mouse L929 cells from TSZ-induced necroptosis with an EC50 of 5.33 nM, and inhibits the phosphorylation of mouse RIPK1 in a dose-dependent manner[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
LT-1339-553 (50-100 mg/kg; p.o.; daily; 4 weeks) significantly alleviates schistosomiasis-induced hepatic fibrosis in C57BL/6 mice, with the 100 mg/kg dose suppressing pro-inflammatory and profibrotic signaling pathways including AKT/PI3K/NF-κB and IL-17[1].
LT-1339-553 (400 mg/kg; p.o.; single dose) exhibits a favorable safety profile in ICR mice with no observed toxicity or organ damage over 14 days[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (infected percutaneously with S. japonicum cercariae, treated with praziquantel at 5 weeks postinfection to clear parasites)[1]
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Dosage:5 mg/kg; 10 mg/kg
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Administration:i.p.; daily; 4 weeks
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Result:Significantly improved body weight recovery at weeks 8 and 9 postinfection compared to infected controls.
Reduced liver index from 8.67% to 6.14% and spleen index from 1.60% to 0.76% at 10 mg/kg.
Reduced serum ALT and AST levels, hepatic egg granuloma area, collagen deposition, liver hydroxyproline content, and liver ROS levels compared to infected controls, with significant effects at 10 mg/kg.
Decreased hepatic protein levels of Collagen I and α-SMA, with the 10 mg/kg dose showing more pronounced reduction.
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Animal Model:C57BL/6 (infected percutaneously with S. japonicum cercariae, treated with praziquantel at 5 weeks postinfection to clear parasites)[1]
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Dosage:50 mg/kg; 100 mg/kg
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Administration:p.o.; daily; 4 weeks
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Result:Significantly improved body weight recovery at weeks 8 and 9 postinfection compared to infected controls.
Reduced liver index, spleen index, serum ALT and AST levels, hepatic egg granuloma area, collagen deposition, liver hydroxyproline content, and liver ROS levels compared to infected controls, with significant effects at both doses.
Decreased hepatic protein levels of Collagen I and α-SMA, with the 100 mg/kg dose showing more pronounced reduction.
Downregulated hepatic expression of inflammatory factors (TNF-α, IL-17, IL-1β) and chemokines (CXCL5/9/10/16, CCL2/4/5/7/11/22), and suppressed activation of the AKT/PI3K/NF-κB signaling pathway and necroptosis-related proteins (RIPK1, RIPK3, MLKL, and their phosphorylated forms) at 100 mg/kg.
Chemical Information
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CAS. Nr. 3078683-57-2
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Molecular Weight 464.34
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Formel C21H13F5N4O3
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SMILES
NC1=NOC2=C1C(C3=C(C(F)=C(C=C3)NC(NC4=CC(OC(F)(F)F)=CC=C4)=O)F)=CC=C2
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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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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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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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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
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)