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.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 95.04%
- Fòrmula: C289H479N79O88S2
- Peso molecular:6532.50
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Almacenamiento:
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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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
Descripciòn
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.
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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 |
|---|---|---|---|---|---|---|---|---|
| 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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Peso molecular 6532.50
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Fòrmula 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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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
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)
Solvente y solubilidad
In Vitro:
DMSO : 10 mg/mL (1.53 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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.
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.
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.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (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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Instrucciones de manejo (2659 KB)
Referencias
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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.1531 mL | 0.7654 mL | 1.5308 mL | 3.8270 mL |
SK56 Related Classifications
HY-P11603 Related Classifications
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