2. Apoptosis Immunology/Inflammation
  3. Pyroptosis
  4. 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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SK56

SK56 Chemical Structure

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SK56 Related Antibodies

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Description

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[1].

In Vitro

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.

SK56 Related Antibodies

Western Blot Analysis[1]

Cell Line: THP-1 cells
Concentration: 15, 45 μM
Incubation Time: 2 h
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.

Immunofluorescence[1]

Cell Line: LPS + nigericin-induced THP-1 cells
Concentration: 15 μM
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%.

Immunofluorescence[1]

Cell Line: LPS + nigericin-induced GSDMD-casp–BFP transfectedBMDMs
Concentration: 20 μM
Incubation Time: 2 h
Result: Inhibited phagocytosis of BMDCs by GSDMD-NT pores on pyroptosis cell membrane fragments.

Immunofluorescence[1]

Cell Line: LPS + nigericin-induced alveolar organoids and THP-1 cells coculture system
Concentration: 15 μM
Incubation Time: 0.5, 4, 8, 12, 16 h
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.

ELISA Assay[1]

Cell Line: LPS + nigericin-induced alveolar organoids and THP-1 cells coculture system
Concentration: 15 μM
Incubation Time: 12 h
Result: Inhibited IL-1β release by approximately 60% compared to PBS at 12 h.
Parmacokinetics
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
In Vivo

SK56 (1-4 mg/kg; intravenous injection; 4, 5, and 16 h after LPS treatment) improves survival rate, alleviates organ damage and systemic inflammation, and regulates immune cell subsets in LPS-induced sepsis mouse models[1].
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.

Animal Model: C57BL/6J mice, WT/Gsdmd−/− (8-10 weeks old, 50:50 female:male ratio, LPS-induced sepsis)[1]
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)
Administration: i.v.; 16 h post-LPS; 5 h post-LPS 25 mg/kg; 4 h post-LPS 50 mg/kg
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.
Animal Model: C57BL/6J mice, WT/Gsdmd−/− (8-10 weeks old, 50:50 female:male ratio, CLP-induced sepsis)[1]
Dosage: 1 mg/kg
Administration: i.v.; 16 h post-CLP
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.
Molecular Weight

6532.50

Formula

C289H479N79O88S2
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
Sequence Shortening

SLEEFAKRVVEELVKEFNLDKRQESYLEMSALIQAQMGISERIIEIVLRHAAQTLK
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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SK56 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

SK56SK 56SK-56PyroptosisGSDMD-NT pore inhibitormacrophagesperipheral blood leukocytessepsis
Inhibitorinhibitorinhibit

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