Design of new inhibitors for cdc2 kinase based on a multiple pseudosubstrate structure.
New inhibitors have been designed for cdc2 kinase based on a multiple pseudosubstrate structure. The new inhibitors have three different structural components: 3,4-bis(indol-3-yl)maleimide, Ac-Cys-(Ser)-Pro-Lys-Lys-NHMe, and ethyloxy group between the two components. Inhibitory activities toward cdc2 and other protein kinases were investigated, and the compound (21) with Ac-Cys-Pro-Lys-Lys-NHMe connected with the triethylene glycol spacer exhibited the most potent inhibition with relatively high selectivity.
Sasaki
S
S
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Hashimoto
T
T
Obana
N
N
Yasuda
H
H
Uehara
Y
Y
Maeda
M
M
D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D019926:Cyclin B / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006657:Histones / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D019926:Cyclin B; D004791:Enzyme Inhibitors; D006657:Histones; D007202:Indicators and Reagents; D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; D016203:CDC2 Protein Kinase