title: A novel class of highly potent, selective, and non-peptidic inhibitor of Ras farnesyltransferase (FTase).
abstract: Design, synthesis and structure-activity relationship of a class of aryl pyrroles as farnesyltransferase inhibitors are described. In vitro and in vivo evaluation of a panel of these inhibitors led to identification of 2 (LB42908) as a highly potent (IC(50)=0.9 nM against H-Ras and 2.4 nM against K-Ras) antitumor agent that is currently undergoing preclinical studies.
authors.affiliation: Life Science R&D, LGCI, Science Town, Taejon 305-380, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Shin
authors.forename: W
authors.initials: W
authors.lastname: Jung
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: K
authors.initials: K
authors.lastname: Park
authors.forename: K
authors.initials: K
authors.lastname: Kim
authors.forename: H S
authors.initials: HS
authors.lastname: Cho
authors.forename: S
authors.initials: S
authors.lastname: Ro
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: S W
authors.initials: SW
authors.lastname: Jeong
authors.forename: T
authors.initials: T
authors.lastname: Choi
authors.forename: H H
authors.initials: HH
authors.lastname: Chung
authors.forename: J S
authors.initials: JS
authors.lastname: Koh
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D010455:Peptides / Q000737:chemistry; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; C448382:LB42908; D010455:Peptides; D010879:Piperazines; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase