GSK583

SKU: orb1304095

Description

GSK583 is a potent and selective inhibitor of RIP2 kinase, exhibiting an IC50 of 5 nM. This compound is a valuable research tool for studying the NOD signaling pathway in both cellular and animal models of inflammatory and autoimmune diseases.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1346547-00-9
• MW: 398.45
• Purity: 99.81% (May vary between batches)
• Formula: C₂₀H₁₉FN₄O₂S
• SMILES: CC(C)(C)S(=O)(=O)c1ccc2nccc(Nc3n[nH]c4ccc(F)cc34)c2c1
• Target: RIP kinase
• Solubility: Ethanol:27 mg/mL (67.76 mM);DMSO:45 mg/mL (112.94 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.02 mM)

Bioactivity

• Target IC50:
  RIP2:5 nM
• In Vivo:
  GSK583 has moderate volumes of distribution, low clearance, and moderate oral bioavailability (in rat and mouse). Although GSK583 would not produce a human pharmacodynamic response within an acceptable dose range, the oral PK in mouse and rat supplies enough systemic exposure for use as a preclinical in vivo tool molecule in an acute inflammation challenge model.
• In Vitro:
  GSK583 possesses a comparable binding affinity for RIP3 kinase similarly to the RIP2 (RIP2/3 FP IC50: 5/16 nM) by an in-house FP binding assay configured. But GSK583 (10 μM) shows little or no inhibition of RIP3-dependent necroptotic cell death in a cellular assay. GSK583 effectively and dose-dependently inhibits MDP-stimulated TNFα production (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 cytokine receptors (IL-1R, TNFR) or Toll-like receptors (TLR2, TLR4, TLR7) but complete inhibition is observed upon activation of NOD1/2 receptors, which signal in a RIP2-dependent manner. Although it has excellent kinase selectivity, GSK583 does inhibit both the hERG channel and CYP3A4.
• Cell Research:
  To assess cellular selectivity, monocytes are pretreated with inhibitor for 30 min, then stimulated for 6 h with ligands which selectively agonize NLRs NOD1, NOD2; Toll-like receptors TLR, TLR4, TLR7, or cytokine receptors IL-1R, TNFR. Release of pro-inflammatory cytokines, either TNFα (NOD2, TLR2, TLR4, IL1R) or IL-8 (NOD1, TLR7, TNFR), is measured by immunoassay. Percent inhibition and/or IC50 values are calculated. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, GSK 583, GSK583, GSK-583, inhibit, RIP3, RIP kinase, RIP1, RIPkinase, RIPK, Receptor-interacting protein kinases

Compound Identifiers

PubChem CID

67469084