SML2102

GSK256066

• Synonym(s): 6-({3-[(Dimethylamino)carbonyl]phenyl}sulfonyl)-8-methyl-4-{[3-(methoxy)phenyl]amino}-3-quinolinecarboxamide, 6-[[3-[(Dimethylamino)carbonyl]phenyl]sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methyl-3-quinolinecarboxamide, GSK 256066, GSK-256066
• Empirical Formula (Hill Notation): C₂₇H₂₆N₄O₅S
• CAS Number: 801312-28-7
• Molecular Weight: 518.58
• MDL number: MFCD18206923
• UNSPSC Code: 51111800

Properties

• Assay: ≥97% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 2 mg/mL, clear
• storage temp.: −20°C
• SMILES string: [S](=O)(=O)(c4cc(ccc4)C(=O)N(C)C)c1cc2c([nH]cc([c]2=Nc3cc(ccc3)OC)C(=O)N)c(c1)C
• InChI: 1S/C27H26N4O5S/c1-16-11-21(37(34,35)20-10-5-7-17(12-20)27(33)31(2)3)14-22-24(16)29-15-23(26(28)32)25(22)30-18-8-6-9-19(13-18)36-4/h5-15H,1-4H3,(H2,28,32)(H,29,30)
• InChI key: JFHROPTYMMSOLG-UHFFFAOYSA-N

Description

Biochem/physiol Actions

GSK256066 is a reversible and cAMP-competitive phosphodiesterase 4 (PDE4) inhibitor that targets all PDE4 subtypes with high affinity (IC50 = 53.7 pM against 2 nM [3H]-rolipram for binding HRBS in rat brain cytosol), potency and selectivity (pIC50 ≥11.31/11.5/11.42/11.94 against PDE4A/B/C/D vs. pIC50 = 5.73/5.92/5.93/5.39/5.28/8.11 against PDE1/2/3/5/6/7 by SPA assays). GSK256066 effectively inhibits LPS-induced TNFα production from human whole blood and isolated PBMCs (pIC50 = 126 and 10 pM, respectively) in vitro and acute pulmonary neutrophilia in rats in vivo (ED50 = 1.1 μg/kg, administered intratracheally 2 hrs priror to LPS). GSK256066 is shown to be more potent than Cilomilast (SB-207499) and Roflumilast in both cell-free and cell-based assays.

Highly potent and selective phosphodiesterase 4 (PDE4) inhibitor that inhibits LPS-induced inflammatory response both in cultures and in rats in vivo.

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3