title: Discovery of novel and selective IKK-beta serine-threonine protein kinase inhibitors. Part 1.
abstract: IkappaB kinase beta (IKK-beta) is a serine-threonine protein kinase critically involved in the activation of the transcription factor Nuclear Factor kappa B (NF-kappaB) in response to various inflammatory stimuli. We have identified a small molecule inhibitor of IKK-beta. Optimization of the lead compound resulted in improvements in both in vitro and in vivo potency, and provided IKK-beta inhibitors exhibiting potent activity in an acute cytokine release model (LPS-induced TNFalpha).
authors.affiliation: Department of Chemistry, Research Center Kyoto, Bayer Yakuhin, Ltd., Kizu, Soraku, Kyoto 619-0216, Japan. toshiki.murata.tm@bayer.co.jp
authors.forename: Toshiki
authors.initials: T
authors.lastname: Murata
authors.forename: Mitsuyuki
authors.initials: M
authors.lastname: Shimada
authors.forename: Sachiko
authors.initials: S
authors.lastname: Sakakibara
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kadono
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Masuda
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimazaki
authors.forename: Takuya
authors.initials: T
authors.lastname: Shintani
authors.forename: Kinji
authors.initials: K
authors.lastname: Fuchikami
authors.forename: Katsuya
authors.initials: K
authors.lastname: Sakai
authors.forename: Hisayo
authors.initials: H
authors.lastname: Inbe
authors.forename: Keisuke
authors.initials: K
authors.lastname: Takeshita
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Masaomi
authors.initials: M
authors.lastname: Umeda
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Bacon
authors.forename: Karl B
authors.initials: KB
authors.lastname: Ziegelbauer
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Lowinger
mesh_terms: D000818:Animals; D002460:Cell Line; D018946:Chemokine CCL5 / Q000032:analysis; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase; D020128:Inhibitory Concentration 50; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D018946:Chemokine CCL5; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse