title: Novel 3-aminopyrazole inhibitors of MK-2 discovered by scaffold hopping strategy.
abstract: New, selective 3-aminopyrazole based MK2-inhibitors were discovered by scaffold hopping strategy. The new derivatives proved to inhibit intracellular phosphorylation of hsp27 as well as LPS-induced TNFalpha release in cells. In addition, selected derivative 14e also inhibited LPS-induced TNFalpha release in vivo.
authors.affiliation: Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. juraj.velcicky@novartis.com
authors.forename: Juraj
authors.initials: J
authors.lastname: Velcicky
authors.forename: Roland
authors.initials: R
authors.lastname: Feifel
authors.forename: Stuart
authors.initials: S
authors.lastname: Hawtin
authors.forename: Richard
authors.initials: R
authors.lastname: Heng
authors.forename: Christine
authors.initials: C
authors.lastname: Huppertz
authors.forename: Guido
authors.initials: G
authors.lastname: Koch
authors.forename: Markus
authors.initials: M
authors.lastname: Kroemer
authors.forename: Henrik
authors.initials: H
authors.lastname: Moebitz
authors.forename: Laszlo
authors.initials: L
authors.lastname: Revesz
authors.forename: Clemens
authors.initials: C
authors.lastname: Scheufler
authors.forename: Achim
authors.initials: A
authors.lastname: Schlapbach
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D011720:Pyrazoles; D000099190:MAP-Kinase-Activated Kinase 2; C436945:3-aminopyrazole