GSK583
Catalog No.S8261
Molecular Weight(MW): 398.45
GSK583 is a highly potent and selective inhibitor of RIP2 kinase with an IC50 of 5 nM.
Purity & Quality Control
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Biological Activity
| Description | GSK583 is a highly potent and selective inhibitor of RIP2 kinase with an IC50 of 5 nM. | ||||
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| In vitro |
GSK583 possesses comparable binding affinity for RIP3 kinase as demonstrated by an in-house FP binding assay configured similarly to the RIP2 FP assay (RIP2 FP IC50 = 5 nM; RIP3 FP IC50 = 16 nM). Despite this potent biochemical activity against RIP3 kinase, GSK583 shows little or no inhibition of RIP3-dependent necroptotic cell death in a cellular assay up to 10 μM concentration. GSK583 potently and dose dependently inhibits MDP-stimulated tumor necrosis factor-alpha (TNFα) production with an IC50 = 8 nM in primary human monocytes. Following treatment with GSK583 at 1 μM, little inhibition of pro-inflammatory signaling is observed upon activation of Toll-like receptors (TLR2, TLR4, TLR7) or cytokine receptors (IL-1R, TNFR) but complete inhibition is observed upon activation of both NOD1 and NOD2 receptors, which signal in a RIP2-dependent manner. Although GSK583 has excellent kinase selectivity, it does inhibit both the hERG channel and Cyp3A4, which precludes it from further progression as a drug candidate[1]. |
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| In vivo | GSK583 has low clearance, moderate volumes of distribution, and moderate oral bioavailability in both rat and mouse. Eventhough GSK583 would not produce a human phamacodynamic response within an acceptable dose range which precludes this molecule from further development as a drug candidate, the oral PK in rat and mouse provides sufficient systemic exposure for use as a preclinical in vivo tool molecule in an acute inflammation challenge model[1]. |
Protocol
| Cell Research: |
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Solubility (25°C)
| In vitro | DMSO | 79 mg/mL (198.26 mM) |
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| Ethanol | 28 mg/mL (70.27 mM) | |
| Water | Insoluble |
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Information
| Molecular Weight | 398.45 |
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| Formula | C20H19FN4O2S |
| CAS No. | 1346547-00-9 |
| Storage | powder |
| in solvent | |
| Synonyms | N/A |
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