SML1960

GSK583

≥98% (HPLC)

• Synonym(s): GSK583, 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine, GSK′583, GSK-2616583A
• Empirical Formula (Hill Notation): C₂₀H₁₉FN₄O₂S
• CAS Number: 1346547-00-9
• Molecular Weight: 398.45
• UNSPSC Code: 51111800
• NACRES: NA.77

Properties

• Quality Level: 100
• Assay: ≥98% (HPLC)
• form: powder
• storage condition: desiccated; protect from light
• color: white to beige
• solubility: DMSO: 20 mg/mL, clear
• storage temp.: 2-8°C
• SMILES string: Fc1cc2c([nH]nc2Nc3c4c(ncc3)ccc(c4)[S](=O)(=O)C(C)(C)C)cc1
• InChI key: XLOGLWKOHPIJLV-UHFFFAOYSA-N

Description

Biochem/physiol Actions

An ATP-competitive RIP2 (RIPK2) inhibitor with in vitro and in vivo efficacy against NOD1- and NOD2-dependent pro-inflammatory cytokines release.

GSK583 is a cell-permeable indazolylquinolinamine that acts as an ATP-competitive (IC50 = 2 & 5 nM using rat & human RIPK2, respectively) inhibitor against RIPK2 kinase activity (66.6% inhibition at 1 μM; [ATP] = 10 μM), exhibiting much reduced or no inhibitory potency against a panel of 209 other kinases <34% inhibition at 1 μM; [ATP] = 10 ?M). GSK583 selectively inhibits against NOD1- and NOD2-, but not TLR2-, TLR4-, TLR7-. IL-1R-, or TNFR-dependent pro-inflammatory cytokines release (>95% inhibition vs. <40% inhibition at 1 ?M using primary human monocytes stimulated with respective ligands). GSK583 effectively inhibits TNF? and IL-6 production from Crohn′s disease (CD) and ulcerative colitis (UC) patients intestinal explant cultures ex vivo (IC50 = 200 nM) and is efficacious against NOD1 ligand FK156- and NOD2 ligand MDP-induced inflammatory responses in mice and rats (10 mg/kg p.o.) in vivo.

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable