SK56
SK56 is a GSDMD-NT pore inhibitor. SK56 inhibits pyroptosis (Pyroptosis) and the release of pyroptosis-related cytokines in macrophages and human peripheral blood leukocytes. SK56 prevents extensive cell death in human alveolar organoids in an organoid-macrophage co-culture model. SK56 prevents death from infectious shock induced by LPS (HY-D1056) or cecal ligation and puncture in mice. SK56 can be used in studies related to sepsis.
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- Fòrmula: C289H479N79O88S2
- Peso molecular:6532.50
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
SK56 (15 μM, 2 h) potently inhibits the release of IL-1β and IL-18, suppresses pyroptosis (IC50 = 1.38 μM) and the release of pyroptotic cell membrane fragments in LPS + nigericin-induced THP-1 cells[1].
SK56 (0.5-15 μM, 0-300 min) increases intracellular ATP levels in a concentration-dependent manner in LPS + nigericin-induced BMDMs, and inhibits pyroptosis via recruiting ESCRT (IC50 = 1.12 μM)[1].
SK56 (15 μM; 0-70 min) translocates into LPS + nigericin-induced THP-1 cells via GSDMD-NT pores, subsequently binds to mitochondria, inhibits ROS accumulation, delays lactate dehydrogenase release, and alleviates mitochondrial injury[1].
SK56 exhibits high affinity for GSDMC-NT-GFP (with a Kd of approximately 0.22 µM) and GSDMD-NT-GFP (with a Kd of approximately 0.25 µM), and blocks the pores formed by GSDMD-NT in PDA nanoparticle hydrogels[1].
SK56 (20 μM, 2 h) inhibits the phagocytosis of GSDMD-NT pores on pyroptotic cell membrane fragments by BMDCs in LPS + nigericin-induced GSDMD-casp-BFP-transfected BMDMs[1].
SK56 (20 μM, 12 h) reduces the secretion of IL-1β in activated BMDCs[1].
SK56 (15 μM, 0.5-16 h) inhibits extensive pyroptosis and protects lung tissue in a co-culture system of human alveolar organoids and THP-1 cells induced by LPS + nigericin[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:THP-1 cells
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Concentration:15, 45 μM
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Incubation Time:2 h
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Result:Exhibited the strongest inhibition of IL-1β.
Inhibited the release of GSDMD-NT in the supernatant by 80% compared to PBS at 45 μM.
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Cell Line:LPS + nigericin-induced THP-1 cells
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Concentration:15 μM
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Incubation Time:0， 20，30, 40,
50, 60, 80 min -
Result:Delayed pyroptosis by about 40 min.
Inhibited SYTOX green influx.
Entered cells through GSDMD-NT pores and subsequently bind to mitochondria, inhibited the decline in MitoTracker red fluorescence by 40%.
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Cell Line:LPS + nigericin-induced GSDMD-casp–BFP transfectedBMDMs
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Concentration:20 μM
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Incubation Time:2 h
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Result:Inhibited phagocytosis of BMDCs by GSDMD-NT pores on pyroptosis cell membrane fragments.
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Cell Line:LPS + nigericin-induced alveolar organoids and THP-1 cells coculture system
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Concentration:15 μM
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Incubation Time:0.5, 4, 8, 12, 16 h
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Result:Reduced the fluorescence delay of calcein-acetoxymethyl ester+ in organoids and THP-1 cells by 50%, and increased the fluorescence delay of PI+ in organoids and THP-1 cells by approximately 8 h.
Reduced the percentage of GSDMD-NT⁺ cells.
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Cell Line:LPS + nigericin-induced alveolar organoids and THP-1 cells coculture system
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Concentration:15 μM
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Incubation Time:12 h
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Result:Inhibited IL-1β release by approximately 60% compared to PBS at 12 h.
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-last | Vss | MRT0-inf |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 2.66 h | 0.08 h | 11.23 μg/mL | 22.827 μg·h/mL | 1.308 μg/mL | 3.351 h |
SK56 (1 mg/kg; i.v.; 16 h post-CLP) exerts protective effects in a mouse model of sepsis induced by cecal ligation and puncture (CLP) by improving mouse survival rate, alleviating organ damage, and reducing systemic cytokine levels[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 mice, WT/Gsdmd−/− (8-10 weeks old, 50:50 female:male ratio, LPS-induced sepsis)[1]
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Dosage:1 mg/kg (post-LPS 15 mg/kg); 2 mg/kg (post-LPS 25 mg/kg); 4 mg/kg (post-LPS 50 mg/kg)
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Administration:i.v.; 16 h post-LPS; 5 h post-LPS 25 mg/kg; 4 h post-LPS 50 mg/kg
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Result:Reduced mortality, alleviated damage to the kidneys, liver, intestines, spleen, and lungs, decreased the expression levels of AST, BUN, ALT, and CK, and reduced the levels of CSF2, IFNγ, IL-1β, IL-2, IL-10, and TNF in peripheral blood.
Reduced the increase of splenic mononuclear cells, inhibited the increase of lung T cells, and restored the number of total immune cells and B cells in peripheral blood.
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Animal Model:C57BL/6J mice, WT/Gsdmd−/− (8-10 weeks old, 50:50 female:male ratio, CLP-induced sepsis)[1]
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Dosage:1 mg/kg
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Administration:i.v.; 16 h post-CLP
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Result:Reduced mortality, alleviated organ damage, decreased the expression levels of blood cytokines CSF2, IL-1β, IL-4, IL-10, and TNF, and reduced the levels of organ damage markers.
Chemical Information
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Peso molecular 6532.50
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Fòrmula C289H479N79O88S2
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Sequence
Ser-Leu-Glu-Glu-Phe-Ala-Lys-Arg-Val-Val-Glu-Glu-Leu-Val-Lys-Glu-Phe-Asn-Leu-Asp-Lys-Arg-Gln-Glu-Ser-Tyr-Leu-Glu-Met-Ser-Ala-Leu-Ile-Gln-Ala-Gln-Met-Gly-Ile-Ser-Glu-Arg-Ile-Ile-Glu-Ile-Val-Leu-Arg-His-Ala-Ala-Gln-Thr-Leu-Lys
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Sequence Shortening
SLEEFAKRVVEELVKEFNLDKRQESYLEMSALIQAQMGISERIIEIVLRHAAQTLK
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SK56 Related Classifications
HY-P11603 Related Classifications
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