A novel class of highly potent, selective, and non-peptidic inhibitor of Ras farnesyltransferase (FTase).
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.
Lee
H
H
Life Science R&D, LGCI, Science Town, Taejon 305-380, Republic of Korea.
Lee
J
J
Lee
S
S
Shin
Y
Y
Jung
W
W
Kim
J H
JH
Park
K
K
Kim
K
K
Cho
H S
HS
Ro
S
S
Lee
S
S
Jeong
S W
SW
Choi
T
T
Chung
H H
HH
Koh
J S
JS
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
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