Pamapimod (C09-1017-224)

InformationPamapimod (R-1503, Ro4402257) is a novel, selective inhibitor ofp38 mitogen-activated protein kinase. It inhibits p38α and p38β enzymatic activity with IC50 values of 0.014±0.002 and 0.48± 0.04 microM, respectively with no activity against p38delta or p38gamma isoforms.Targetsp38α (Cell-free assay); p38β (Cell-free assay) 0.014 μM; 0.48 μMIn vitroPamapimod inhibited p38, but inhibition of JNK was not detected. Pamapimod also inhibited lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) α production by monocytes, interleukin (IL)-1β production in human whole blood, and spontaneous TNFα production by synovial explants from RA patients.In vivoIn murine collagen-induced arthritis, pamapimod reduced clinical signs of inflammation and bone loss at 50 mg/kg or greater. In a rat model of hyperalgesia, pamapimod increased tolerance to pressure in a dose-dependent manner, suggesting an important role of p38 in pain associated with inflammation. Pamapimod suppresses spontaneous production of TNFα by synovial explants from RA patients. LPS- and TNFα-stimulated production of TNFα and IL-6 in rodents also was inhibited by pamapimod.Cell Research(from reference)Cell lines：Human Monocytic Cell Line, THP-1 Concentrations：15 μM Incubation Time：150 min. Specifications and Purity: 99%. Molecular Formula: C19H20F2N4O4. Molecular Weight: 406.38. PubChem CID: 16220188. Isomeric SMILES: CN1C2=NC(=NC=C2C=C(C1=O)OC3=C(C=C(C=C3)F)F)NC(CCO)CCO.