title: Structure-based lead identification of ATP-competitive MK2 inhibitors.
abstract: MK2 kinase is a promising drug discovery target for the treatment of inflammatory diseases. Here, we describe the discovery of novel MK2 inhibitors using X-ray crystallography and structure-based drug design. The lead has in vivo efficacy in a short-term preclinical model.
authors.affiliation: Merck Research Laboratories, MSD, Oss, The Netherlands.
authors.forename: Tjeerd
authors.initials: T
authors.lastname: Barf
authors.forename: Allard
authors.initials: A
authors.lastname: Kaptein
authors.forename: Sander
authors.initials: S
authors.lastname: de Wilde
authors.forename: Ruud
authors.initials: R
authors.lastname: van der Heijden
authors.forename: Richard
authors.initials: R
authors.lastname: van Someren
authors.forename: Dennis
authors.initials: D
authors.lastname: Demont
authors.forename: Carsten
authors.initials: C
authors.lastname: Schultz-Fademrecht
authors.forename: Judith
authors.initials: J
authors.lastname: Versteegh
authors.forename: Mario
authors.initials: M
authors.lastname: van Zeeland
authors.forename: Nicole
authors.initials: N
authors.lastname: Seegers
authors.forename: Bert
authors.initials: B
authors.lastname: Kazemier
authors.forename: Bas
authors.initials: B
authors.lastname: van de Kar
authors.forename: Maaike
authors.initials: M
authors.lastname: van Hoek
authors.forename: Jeroen
authors.initials: J
authors.lastname: de Roos
authors.forename: Henri
authors.initials: H
authors.lastname: Klop
authors.forename: Ruben
authors.initials: R
authors.lastname: Smeets
authors.forename: Claudia
authors.initials: C
authors.lastname: Hofstra
authors.forename: Jorrit
authors.initials: J
authors.lastname: Hornberg
authors.forename: Arthur
authors.initials: A
authors.lastname: Oubrie
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D001667:Binding, Competitive; D018938:Caco-2 Cells; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000255:Adenosine Triphosphate; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2