1. Apoptosis
  2. RIP kinase

GSK583 

Cat. No.: HY-100339 Purity: 98.07%
Handling Instructions

GSK583 is a highly potent and selective inhibitor of RIP2 Kinase, with IC50 of 5 nM.

For research use only. We do not sell to patients.

GSK583 Chemical Structure

GSK583 Chemical Structure

CAS No. : 1346547-00-9

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 147 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
2 mg USD 84 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
5 mg USD 168 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
10 mg USD 264 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
50 mg USD 900 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
100 mg USD 1440 In-stock
Stock in the United States
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

    GSK583 purchased from MCE. Usage Cited in: J Immunol. 2017 May 1;198(9):3729-3736.

    Confocal images of lysozyme and procryptdin in cultured WT crypt organoids treated with GSK583 (5 μM) or mock-treated (A), or WEHI-345 (2.5 μM) or mock-treated (B) for 16 hours.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    GSK583 is a highly potent and selective inhibitor of RIP2 Kinase, with IC50 of 5 nM.

    IC50 & Target

    IC50: 5 nM (RIP2K)[1]

    In Vitro

    GSK583 (1 μM) exhibits excellent selectivity in a panel of 300 kinases, including p38α and VEGFR2. GSK583 potently and dose dependently inhibits MDP-stimulated tumor necrosis factor-alpha (TNFα) production with an IC50 of 8 nM. GSK583 demonstrates only a modest reduction in potency when profiled in a similar MDP-induced TNFα production assay in human whole blood (IC50 = 237 nM) and rat whole blood (IC50 = 133 nM)[1].

    In Vivo

    GSK583 (0.1, 1, and 10 mg/kg, p.o.) inhibits serum KC (the rodent orthologue of IL-8) levels in rats in a dose-dependent manner, with an IC50 derived from rat blood concentrations of 50 nM (or 20 ng/mL). Similarly, GSK583 inhibits serum KC levels and recruitment of neutrophils into the peritoneal cavity in mice in a dose-dependent manner, with an IC50 of 37 nM (15 ng/mL) derived from mouse blood concentration[1].

    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 37 mg/mL (92.86 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.5097 mL 12.5486 mL 25.0972 mL
    5 mM 0.5019 mL 2.5097 mL 5.0195 mL
    10 mM 0.2510 mL 1.2549 mL 2.5097 mL
    *Please refer to the solubility information to select the appropriate solvent.
    References
    Kinase Assay
    [1]

    A fluorescent polarization based binding assay is developed to quantitate interaction of novel test compounds at the ATP binding pocket of RIP2K by competition with a fluorescently labeled ATP competitive ligand. Full length FLAG His tagged RIP2K is purified from a baculovirus expression system and is used at a final assay concentration of twice the KD apparent. A fluorescent labeled ligand that is reversible and competitive with the inhibitors is used at a final assay concentration of 5 nM. Both the enzyme and ligand are prepared in solutions in 50 mM HEPES pH 7.5, 150 mM NaCl, 10 mM MgCl2, 1 mM DTT, and 1 mM CHAPS. Test compounds are prepared in 100% DMSO, and 100 nL is dispensed to individual wells of a multiwell plate. Next, 5 μL of RIP2K is added to the test compounds at twice the final assay concentration and incubated at room temperature for 10 min. Following the incubation, 5 μL of the fluorescent labeled ligand solution is added to each reaction at twice the final assay concentration and incubated at room temperature for at least 10 min. Finally, samples are read on an instrument capable of measuring fluorescent polarization. Test compound inhibition is expressed as percent (%) inhibition of internal assay controls. For concentration response experiments, normalized data are fit using the following four parameter logistic equation: y = A + ((B-C))/(1+(10x)/(10C)D), where y is the % activity (% inhibition) at a specified compound concentration, A is the minimum % activity, B is the maximum % activity, C = log10(IC50), D = Hill slope, x = log10(compound concentration [M]), and pIC50 = (−C).

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Mice[1]
    Female C57Bl/6 mice (for cytokine analyses) or male Balb/c mice (for peritoneal neutrophil analyses) (n=10/treatment group) are dosed orally 15 min prior to MDP challenge with vehicle or GSK583 (0.1, 1, or 10 mg/kg). For peritoneal neutrophil analysis, mice are sacrificed at 4 h post-MDP challenge (30 μg, i.p.) and peritoneal fluid is collected by lavage. Peritoneal neutrophils are quantified by FACS analysis.
    Rats[1]
    Female Crl:CD(SD) rats (n=8/treatment group) are dosed orally with vehicle or GSK583 15 min prior to MDP challenge (150 μg/rat, IV). At 2 h post MDP challenge, rats are sacrificed and terminal serum is prepared from blood collected via cardiac stick. Serum cytokine levels (IL-6, IL-8 or KC, IL-1β, and TNFα) are quantified by the MSD platform.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    398.45

    Formula

    C₂₀H₁₉FN₄O₂S

    CAS No.

    1346547-00-9

    SMILES

    FC1=CC2=C(NN=C2NC3=CC=NC4=CC=C(S(=O)(C(C)(C)C)=O)C=C34)C=C1

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

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    Product Name:
    GSK583
    Cat. No.:
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    Cat. No.: HY-100339