GSK583

GSK583 is a highly potent, orally active and selective inhibitor of RIP2 Kinase, with IC50 of 5 nM. GSK583 inhibits both TNF-α and IL-6 production with an IC50 value of 200 nM.

Product information

CAS Number: 1346547-00-9

Molecular Weight: 398.45

Formula: C20H19FN4O2S

Chemical Name: N-(5-fluoro-1H-indazol-3-yl)-6-(2-methylpropane-2-sulfonyl)quinolin-4-amine

Smiles: CC(C)(C)S(=O)(=O)C1=CC2C(C=C1)=NC=CC=2NC1=NNC2=CC=C(F)C=C21

InChiKey: XLOGLWKOHPIJLV-UHFFFAOYSA-N

InChi: InChI=1S/C20H19FN4O2S/c1-20(2,3)28(26,27)13-5-7-16-14(11-13)17(8-9-22-16)23-19-15-10-12(21)4-6-18(15)24-25-19/h4-11H,1-3H3,(H2,22,23,24,25)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : ≥ 100 mg/mL (250.97 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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).

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.

References:

1. Haile PA et al. The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase. J Med Chem, 2016 May 26, 59(10):4867-80.

Products are for research use only. Not for human use.