SK56
Based on 1 Customer Validation
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.
For research use only. We do not sell to patients.
- Purity : 95.19%
- Formula: C289H479N79O88S2
- Molecular Weight:6532.50
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Storage:
Sealed storage, away from moisture.
Powder -80°C, 2 years , -20°C, 1 year* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
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. Further protocols information, click here.
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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.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-last | Vss | MRT0-inf |
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| 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 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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Appearance Solid
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Molecular Weight 6532.50
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Formula C289H479N79O88S2
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Color White to off-white
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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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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Sealed storage, away from moisture
Powder -80°C 2 years -20°C 1 year * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
In Vitro:
H2O : 8.33 mg/mL (1.28 mM; Need ultrasonic)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 1 mg/mL (0.15 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 1 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
Protocols
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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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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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LPS-Induced Endotoxemia/Systemic Inflammation
Lipopolysaccharide (LPS)-induced endotoxemia is a widely used in vivo model of acute systemic inflammation in which LPS, a Gram-negative bacterial endotoxin, activates innate immune signaling primarily through TLR4, leading to rapid and transient induction of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β in circulation and tissues. This cytokine surge is commonly used as a measurable readout of systemic inflammatory activation and immune dysregulation, and is typically assessed within hours after intraperitoneal LPS administration in mouse models of endotoxemia. The model captures key features of systemic inflammatory response syndrome, including cytokine release, immune cell activation, and downstream tissue responses, and has been used to evaluate anti-inflammatory interventions such as cytokine modulation, lipid mediators, and immune cell-targeting therapies.
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Neuron-Astrocyte Co-culture
Neuron-astrocyte co-culture is used to study how astrocytes regulate neuronal survival, synapse formation, dendritic morphology, neuronal activity, and disease-related neurotoxicity. Indirect “sandwich” or insert-based designs physically separate neurons and astrocytes while allowing soluble astrocyte-derived factors to affect neurons, whereas direct co-culture permits cell-contact and network-level readouts.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Pyroptosis Solutions
Pyroptosis is a lytic inflammatory cell-death pathway executed by gasdermin pores, most classically through inflammasome-mediated activation of caspase-1, cleavage of gasdermin D, membrane pore formation, LDH release, and secretion of IL-1β and IL-18. The canonical pathway is commonly modeled by priming cells with an inflammatory signal such as LPS to induce pro-IL-1β and inflammasome components, followed by an activation signal such as ATP or nigericin to activate NLRP3, ASC speck formation, caspase-1 cleavage, GSDMD cleavage, cytokine release, and pyroptotic membrane rupture. The non-canonical pathway is triggered when cytosolic LPS activates mouse caspase-11 or human caspase-4/5, leading to GSDMD cleavage and pyroptosis, and this can secondarily activate NLRP3-dependent IL-1β release. Pyroptosis is linked to inflammatory injury, infection, cancer, liver disease, ocular disease, placental inflammation, and other disease phenotypes, but unresolved questions include which gasdermin fam
Purity & Documentation
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Data Sheet (303 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| H2O | 1 mM | 0.1531 mL | 0.7654 mL | 1.5308 mL | 3.8270 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
SK56 Related Classifications
HY-P11603 Related Classifications
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