title: 4-Anilino-6-phenyl-quinoline inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2).
abstract: A class of inhibitors of mitogen activated protein kinase-activated kinase 2 (MK2) was discovered via high-throughput screening. This compound class demonstrates activity against the enzyme with sub-microM IC(50) values, and suppresses LPS-induced TNFalpha levels in THP-1 cells. MK2 inhibition kinetic measurements indicated mixed binding approaching non-ATP competitive inhibition.
authors.affiliation: Department of Biological Sciences, AstraZeneca R&D Lund, S-22187 Lund, Sweden.
authors.forename: Henric
authors.initials: H
authors.lastname: Olsson
authors.forename: Peter
authors.initials: P
authors.lastname: Sjö
authors.forename: Oguz
authors.initials: O
authors.lastname: Ersoy
authors.forename: Anna
authors.initials: A
authors.lastname: Kristoffersson
authors.forename: Joakim
authors.initials: J
authors.lastname: Larsson
authors.forename: Bo
authors.initials: B
authors.lastname: Nordén
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D057166:High-Throughput Screening Assays; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000634:Aminoquinolines; D000814:Aniline Compounds; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha; D000099190:MAP-Kinase-Activated Kinase 2; C037219:quinoline