title: The discovery of carboline analogs as potent MAPKAP-K2 inhibitors.
abstract: The discovery of a series of potent, carboline-based MK2 inhibitors is described. These compounds inhibit MK2 with IC50s as low as 10 nM, as measured in a DELFIA assay. An X-ray crystal structure reveals that they bind in a region near the p-loop and the hinge region of MK2a.
authors.affiliation: Research and Development, Boehringer-Ingelheim Pharmaceuticals, 900 Ridgebury Road, Ridgefield, CT 06877, USA. jwu@rdg.boehringer-ingelheim.com
authors.forename: Jiang-Ping
authors.initials: JP
authors.lastname: Wu
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.forename: Asitha
authors.initials: A
authors.lastname: Abeywardane
authors.forename: Denise
authors.initials: D
authors.lastname: Andersen
authors.forename: Michel
authors.initials: M
authors.lastname: Emmanuel
authors.forename: Elda
authors.initials: E
authors.lastname: Gautschi
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Goldberg
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Kashem
authors.forename: Susan
authors.initials: S
authors.lastname: Lukas
authors.forename: Wang
authors.initials: W
authors.lastname: Mao
authors.forename: Leslie
authors.initials: L
authors.lastname: Martin
authors.forename: Tina
authors.initials: T
authors.lastname: Morwick
authors.forename: Neil
authors.initials: N
authors.lastname: Moss
authors.forename: Christopher
authors.initials: C
authors.lastname: Pargellis
authors.forename: Usha R
authors.initials: UR
authors.lastname: Patel
authors.forename: Lori
authors.initials: L
authors.lastname: Patnaude
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Peet
authors.forename: Donna
authors.initials: D
authors.lastname: Skow
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Snow
authors.forename: Yancey
authors.initials: Y
authors.lastname: Ward
authors.forename: Brian
authors.initials: B
authors.lastname: Werneburg
authors.forename: Andre
authors.initials: A
authors.lastname: White
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D002243:Carbolines / Q000737:chemistry* / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002243:Carbolines; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2