3gfe | pdb_00003gfe

Crystal Structure of p38a Mitogen-Activated Protein Kinase in Complex with a Pyrazolopyridinone Inhibitor

spinqualitylabelsall models 3gfe, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3gfe is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: P37 Related: 1yqj, 3dt1, 3ds6 Gene: MAPK14, CSBP, CSBP1, CSBP2, CSPB1, MXI2 (Homo sapiens) Activity: Mitogen-activated protein kinase, with EC number 2.7.11.24 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed A novel class of fused pyrazole-derived inhibitors of p38alpha mitogen-activated protein kinase (MAPK) is disclosed. These inhibitors were evaluated for their ability to inhibit the p38alpha enzyme, the secretion of TNFalpha in a LPS-challenged THP1 cell line and TNFalpha-induced production of IL-8 in 50% human whole blood. This series was optimized through a SAR investigation to provide inhibitors with IC(50) values in the low single-digit nanomolar range in whole blood. Further investigation of their pharmacokinetic profiles led to the identification of two potent and orally bioavailable p38 inhibitors 10 m and 10 q. Inhibitor 10 m was found to be efficacious in vivo in the inhibition of TNFalpha production in LPS-stimulated Lewis rats with an ED(50) of 0.1mg/kg while 10 q was found to have an ED(50) of 0.05-0.07 mg/kg. Part 1: Structure-Activity Relationship (SAR) investigations of fused pyrazoles as potent, selective and orally available inhibitors of p38alpha mitogen-activated protein kinase.,Wurz RP, Pettus LH, Xu S, Henkle B, Sherman L, Plant M, Miner K, McBride H, Wong LM, Saris CJ, Lee MR, Chmait S, Mohr C, Hsieh F, Tasker AS Bioorg Med Chem Lett. 2009 Aug 15;19(16):4724-8. Epub 2009 Jun 17. PMID:19574047 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mitogen-activated protein kinase

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