title: Discovery of an in vitro and in vivo potent resorcylic lactone analog of LL-Z1640-2 as anti-inflammatory lead, II.
abstract: The potent in vitro lead compound, ER-803064 (2), a MEK1 and MEKK1 inhibitor inspired from natural product LL-Z1640-2 (f152A1), was further optimized to improve in vitro and in vivo potency. The modifications on C14 position led to discovery of the lead compounds 28 and 29, which regained full in vitro potency of f152A1 and showed higher in vivo potency by iv administration.
authors.affiliation: Eisai Inc., Andover, MA 01810, USA.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Shen
authors.forename: Hong
authors.initials: H
authors.lastname: Du
authors.forename: Makoto
authors.initials: M
authors.lastname: Kotake
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsushima
authors.forename: Masaki
authors.initials: M
authors.lastname: Goto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shirota
authors.forename: Fabian
authors.initials: F
authors.lastname: Gusovsky
authors.forename: Xiangyi
authors.initials: X
authors.lastname: Li
authors.forename: Yimin
authors.initials: Y
authors.lastname: Jiang
authors.forename: Shawn
authors.initials: S
authors.lastname: Schiller
authors.forename: Mark
authors.initials: M
authors.lastname: Spyvee
authors.forename: Heather
authors.initials: H
authors.lastname: Davis
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Robert
authors.initials: R
authors.lastname: Pelletier
authors.forename: Megumi
authors.initials: M
authors.lastname: Ikemori-Kawada
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Atsushi
authors.initials: A
authors.lastname: Inoue
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055808:Drug Discovery; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; C118715:LL Z1640-2; D007783:Lactones; D048369:MAP Kinase Kinase 1